A CLINICAL STUDY OF THE EFFECT OF KANCHANARA GUGGULU AND

SIGRU PATRA KWADHA ON HYPOTHYROIDISM

Dissertation submitted in partial fulfilment for the degree of

DOCTOR OF MEDICINE (AYURVEDA) In

KAYACHIKITSA

By

Dr.V. Vijaya lakshmi prasuna B.A.M.S.

GUIDE Dr. PRAKASH CHANDER

M.D. (Ay.) Professor & HOD,

Post Graduate Dept.of Kayachikitsa Dr. B.R.K.R. Govt.Ayurvedic College,

Hyderabad.

Dr. N.T.R UNIVERSITY OF HEALTH SCIENCES VIJAYAWADA

Dr.BRKR Govt. Ayurvedic College, HYDERABAD 2007

Dr. N.T.R. UNIVERSITY OF HEALTH SCIENCES VIJAYAWADA

POST GRADUATE DEPARTMENT OF KAYACHIKITSA

Dr. B.R.K.R. GOVT. AYURVEDIC MEDICAL COLLEGE / HOSPITAL HYDERABAD

CERTIFICATE

This is to certify that the present dissertation embodies the outcome of original observations made by Dr. V. Vijaya Lakshmi Prasuna on ‘A Clinical Study on the effect of Kanchanara Guggulu and Shigru patra kwatha on

Hypothyroidism’’ for the degree of ‘Doctor of Medicine’ (Ayurveda). This

work has been completed under my direct supervision after a series of a scientific discussion. The scholar has put in commendable effort for designing and executing the methods

and plans for the study. Hence I recommend this dissertation to be submitted for adjudication.

GUIDE Date: Dr. PRAKASH CHANDER Place: Hyderabad. MD (Ayu) Professor& HOD, Post graduate Department of Kayachikitsa Dr. BRKR Govt. Ayurvedic Medical College, Hyderabad.

Dr. N.T.R. UNIVERSITY OF HEALTH SCIENCES VIJAYAWADA

POST GRADUATE DEPARTMENT OF KAYACHIKITSA

Dr. B.R.K.R. GOVT. AYURVEDIC MEDICAL COLLEGE / HOSPITAL HYDERABAD

CERTIFICATE

This is to certify that Dr. V. Vijaya Lakshmi Prasuna of M.D. (Ayu) Kayachikitsa has worked for the thesis on the topic ‘A Clinical Study of the effect of Kanchanara Guggulu and Shigru patra kwatha on Hypothyroidism’’ as per requirements of the order laid by the N.T.R. University of Health Sciences, for the purpose. The hypothesis submitted by her in the first year MD (Ayu) is one and the same to that of the dissertation submitted.

I am fully satisfied with her work and hereby forward the dissertation for the evaluation of the adjudicators.

Date: Dr.PRAKASH CHANDER Place: Hyderabad MD (Ayu) Professor& HOD, Post graduate Dept. of Kayachikitsa Dr BRKR Govt. Ayurvedic Medical College, Hyderabad.

CONTENTS

CHAPTER Page no’s PART-I

1. Introduction. 2. Historical aspect of Hypothyroidism. 3. Shareera:

i) Anatomy. ii) Physiology. iii) Role of iodine. iv) Physiological actions of thyroid hormone.

PART-II

1. Etiology 2. Pathogenesis 3. Clinical features 4. Pathology of hypothyroidism 5. Investigations 6. Complications 7. Goiter 8. Ayurvedic Aspect

i. Galaganda ii. Ayurvedic Aspect of Hypothyroidism

9. Sadhyadsadhya’s PART-III

1. Chikitsa yojana 2. Pathyapathya

PART-IV

1. Criteria for selection. 2. Kanchanara guggulu. 3. Sigru

PART-V

1. Materials and methods. 2. Observations and Results. 3. Discussion. 4. Conclusion. 5. Summary.

REFERENCES APPENDICES

1. Bibliography 2. Case sheet 3. BMI Chart.

ACKNOWLEDGEMENTS

I offer my humble and sincere prostrations to the lotus feet of my

Sadguru Sri Sri Sri Ganapathi Sacchidananda Swamiji for his ever lasting

support and guidance, which have had a profound influence on my life.

I would like to express my gratitude and respect to my guide

Dr. Prakash chander, professor, HOD, PG Dept of Kaya Chikitsa, Hyderabad,

for giving me the opportunity to work in a very interesting area and for his support

and guidance during my thesis work.

My most sincere thanks to Dr. M Srinivasulu for his advice,

confidence and the vision, that started this project and for his constant

encouragement through out my thesis work.

I am especially grateful to Dr. V.Vijay Babu, Reader, P.G Dept of

Kaya Chikitsa, for sharing with me his wealth of knowledge, his valuable

suggestions made me complete my thesis work. I would have been lost without

him.

It is difficult to overstate my gratitude to Dr. PVV Satyanarayana

M.D (Gen) Associate professor, Rangaraya Medical College, Kakinada. With his

enthusiasm, his inspiration and his great efforts to explain things clear and simply,

helped to make my thesis work without any trouble.

I would like to express my sincere thanks to Dr. B. Venkataiah,

HOD Shalakya Dept, Dr. Ravindranath, Dr. J. Srinivasulu,Dr. RCM Sharma

M.D(Homeo), for their valuable suggestions and useful discussions during my

studies.

I express my sincere thanks to my lecturers Dr. M L Naidu, Dr. M.

Bhaswantha Rao, Dr. Ramalingeswara Rao, Dr. Vijayalakshmi for their useful

suggestions.

It’s a pleasure to express my gratitude towards my seniors Dr.

Badrinarayana, Dr. Amaranath, my classmates Dr. Lavanya, Dr.K Sirisha,

Dr.Priya, Dr. Sivanarayana, Dr. Perumal, Dr. Gayatri, Dr. Govindamma for all the

emotional support, companionship, entertainment and caring they provided.

My heartfelt thanks to Mr. Dattu Rao, Mr. Udaypal Yadav,

Mr.Maheswara Singh of Pathology Dept. Ayurvedic Hospital, and Mr. Sunder Raj

of thyrocare center for their collaboration during the investigations.

It is immense pleasure to convey my thanks to my brother Mr. Kali

charan, M.Tech (CS), for his affectionate guidance in the computer work.

I am forever indebted to my parents for their understanding,

endless patience and encouragement. Special thanks to my mother. I have no

words to express my gratitude for her encouragement, inspiration and compassion

and love for me.

Finally I like to thank all my patients for their kind cooperation.

Dr. PRASUNA

LIST OF FIGURES

S.No. Name of the diagram Page No.

1. 1.1 Anatomy of the thyroid gland.

2. 1.2 Detailed anatomy of the thyroid gland.

3. 1.3 Histology of the thyroid gland.

4. 1.4 Thyroid hormone synthesis.

5. 1.5 Thyroid hormone synthesis in detail.

6. 1.6 Thyroid hormone synthesis and structure.

7. 1.7 Metabolism of thyroid hormones

8. 4.1 Kanchanara guggulu and Shigru kwatha churnam.

9. 4.2 Guggulu

10. 4.3 Kanchanara

11. 4.4 Shigru

LIST OF TABLES

S.No. Name of the Table Pg. No.

1. 1.1. The kinetics of thyroid hormones.

2. 1.2. The physiological actions of thyroid hormones on different systems

3. 2.1. The normal and abnormal functions of agni related to Hypothyroidism.

4. 5.1 Incidence of hypothyroidism a/c to Age.

5. 5.2 Incidence of hypothyroidism a/c to Sex.

6. 5.3 Incidence of hypothyroidism a/c to Occupation.

7. 5.4 Incidence of hypothyroidism a/c to SES.

8. 5.5 Incidence of hypothyroidism a/c to Diet

9. 5.6 Incidence of hypothyroidism a/c to Family history.

10. 5.7. Incidence of hypothyroidism a/c to Previous drug/ medical history

11. 5.8 Incidence of hypothyroidism a/c to Prakriti.

12. 5.9 Incidence of hypothyroidism a/c to Sara.

13. 5.10 Incidence of hypothyroidism a/c to BMI.

14. 5.11 TSH levels before and after treatment in fresh cases

15. 5.12 TSH levels before and after treatment in chronic cases.

16. 5.13. The symptomatic relief percentage

17. 5.14. The result of over all treatment.

Introduction

INTRODUCTION

Thyroid gland is one of the most important and sensitive endocrine

gland. As it easily responds to stress and stimuli the global incidence of

hypothyroidism is increasing day by day.

Hypothyroidism occurs when the thyroid gland fails to produce

enough thyroid hormone. Recent studies show that nearly 10% of the population is

suffering from hypothyroidism.

As all the drugs used in this condition are well known for their side

effects a need arises to search a safer drug with similar efficacy.

Due to inadequate success in combating the disease with modern

medications, there is an increasing demand to treat the diseases with Ayurvedic

system of medicine.

Like many other diseases of the modern days it is not mentioned

(exact correlation yet to be made) in Ayurvedic texts.

The recent research work done by Dr. Tripathi and others. Animal

studies have revealed that guggul supports healthy thyroid function, mostly by

increasing the conversion of less active Thyroxin (T4) to more active

Triiodotyronine (T3) through increasing thyroid proteolytic activity and the uptake

of iodine into thyroxin, and without increasing the production of Thyroid

Stimulating Hormone.

As Hypothyroidism results from the under active thyroid gland, the

thyroid stimulatory drug is beneficial here.

The present trial drug kanchanara guggulu (Sa. Sam), is found in

usage for many years for Gandhamala, Apache, Arbuda, Grandhi, Kushta, etc, has

Hypothyroidism 1

Introduction

been selected to evaluate the efficacy of this drug in hypothyroidism. Its many

ingredients kanchanara, varuna, triphala, trikatu, trijataka may also useful in

hypothyroidism.

Sigru is a well-known plant in India. It is rich in iodine, which is an

essential component of thyroid hormones, T3 and T4. It has deepana, pacahna,

kapha vata hara properties. It is recommended in galaganda, kandu, sotha, apachi,

vrana, medoroga, vidradhi, gulma etc.is selected as anupana along with KNG. It

appears to provide it with the nutrition and substitutes the Iodine, thyroid gland

require. Hence the drug is selected for the study.

The main aim of the study is

1. To normalize the levels of TSH in the fresh cases.

2. To maintain the TSH levels in the patients who are already using

the allopathic drug thyronorm and gradually replacing the

allopathic drug with the trail drug.

For fresh cases the trial drug started immediately after the diagnosis

confirmed.

For the patients who are already using thyronorm they were advised

to withdraw the 25 mcg of the drug before starting the trail drug. The patients were

observed carefully for 1 month, if they are comfortable with the drug and dosage

and TSH levels are maintained well they are advised to withdraw another 25mcg.

This way the drug will be totally replaced with the trail drug.

The trail was conducted on 32 patients from the Govt Ayurvedic

Hospital, Erragadda; the progress of the patient is observed and recorded. Analysis

was made to assess the results in relation to various factors.

Hypothyroidism 2

Historical aspects

ENDOCRINOLOGY: HISTORICAL LANDMARKS

The history of thyroid disease is an example f the close inter-

relationship of basic and clinical sciences. Although we can see a slow

advancement in knowledge about the clinical features of thyroid disease since the

dawn of the 20th century, the methods of investigation and treatment advanced

rapidly.

Some endocrine facts, such as the sequel of castration, are deeply

rooted in the past. Frederick Ruysch, a Dutch anatomist, was the first to

speculate, in 1690, that an organ such as the thyroid pours into the blood

substances of physiological importance1. The French scientist Theophile de

Bordeu had a similar theory 1.The Ruysch and Bordeu speculations were easily

criticized by the lack of any experimental proof. But the real father of

endocrinology who set its principles as a formal discipline was French

physiologist Claude Bernard. In 1855, Bernard introduced the term “internal

secretions”

By the end of the 19th century a number of diseases such as Graves

disease and acromegaly were described along with their probable relation to a

glandular dysfunction2. English physiologists, William Bayliss and Ernest

Starling isolated a substance, giving it the name “secretin”. When secretin was

injected into the bloodstream of an experimental animal, it resulted in marked

increased secretion from the pancreas. This result reinforced Bernard’s concept of

internal secretion2 In 1905 Starling coined the term “hormone” for this internal

secretion (including his secretin). The word hormone was derived from a Greek

phrase meaning “to set in motion”. Thus, secretin was the first hormone to be

isolated.

Hypothyroidism 3

Historical aspects

The history of endocrinology is not complete without a mention of

the master of the endocrine glands, the pituitary. The pituitary gland was named

by the Belgian anatomist Andreas Vesalius who believed that it secreted mucus

through the nose (derived from the Latin word pituita which means mucus)1.

Later, the German physician Conrad Victor Schneider cast doubt on the mucus

secreting function of the pituitary when he first described the cribriform plate of

the ethmoid1. But this view persisted until Pierre Marie detected two cases of

acromegaly with associated pituitary enlargement in 1886 and 18882. Since then a

large body of knowledge has accumulated about the pituitary which led Langdon

Brown in 1935 to describe it as the “leader of the endocrine orchestra”.

ANATOMY OF THE THYROID

The anatomy of the thyroid gland can be traced back as far as the

first century AD when Galen, the famous Greek doctor, briefly described it. In

1543 Vesalius gave a full description of the organ; he believed that it consisted of

two separate parts1. Later, the anatomist Bartolomeo Eustachius recognized the

isthmus and considered the thyroid as a single organ1. But the controversy about

whether the thyroid was a single or double organ was finally resolved by

Giovanni Bathista Morgagni who demonstrated that the gland had two lobes

connected by the isthmus. Thomas Wharton of London named the thyroid in

1656, from the Greek word thyreos meaning “oblong shield”2. The histology of

the thyroid was studied from the start of the microscopy era.

PHYSIOLOGY OF THE THYROID

Throughout history, the function of the thyroid has been

controversial. Galen suggested that it functioned to lubricate the larynx and this

view was accepted for a long time. Wharton in 1656 suggested that the purpose

of the thyroid was to beautify the neck by giving it a rounded contour through

Hypothyroidism 4

Historical aspects filling the vacant spaces around the larynx2. In 1829 Astley Cooper proposed that

the thyroid was a lymphatic gland when he noticed lymph passing from it to the

thoracic duct1.

Even up to 1880 the thyroid was proposed as a receptacle of worms

or even a vascular shunt to cushion the brain against a sudden increase in blood

flow. Thomas King first suggested the concept of an internal secretary function

for the thyroid. King’s idea was that the thyroid formed and secreted a vital

material into the circulation at a time of emergency.

In 1856 Moritz Schiff of Berne carried out thyroidectomies on dogs

and guinea pigs with fatal results2. French physiologist Eugene Gley described the

parathyroid glands in 1891. In 1882–83, Ludwig Rehn and Jacques-Louis

Reverdin noticed the appearance of symptoms of hypothyroidism after

thyroidectomy operations on patients with Graves disease. In 1884 Schiff carried

out experiments on dogs and succeeded in preventing the effects of thyroidectomy

by grafting the thyroid onto another part of the animal body. Unfortunately, the

body soon absorbed the gland. Thereafter, the function of the thyroid gland was

thought to neutralize or remove poisons from the body and hence that thyroid

deficiency leads to toxaemia.

The definite function of the thyroid as a controller of metabolism

was studied and confirmed by George Murray, Hector Mackenzie and Edward

Fox. These studies were based on following up the successful effects of giving

thyroid extracts by different routes to patients with myxoedema. From around

1895 thyroid researchers began to study the chemistry of the gland secretions. This

field was pioneered by Eugen Baumann, who was the first to recognize the role

of iodine in the work of the thyroid gland when he discovered a high concentration

Hypothyroidism 5

Historical aspects in the gland. In1896, he isolated a compound containing iodine (iodothyrin) and

suggested a relation to iodine metabolism. In the same year, English pediatrician

Robert Hutchison found that iodine was concentrated in the colloidal material

within the glandular follicles.

In 1899 Oswald extracted an iodized protein which he termed

“thyeroglobin”. The presence of organic iodine in the plasma was indicated by

Gley and Bourcet in 1900 whereas in 1905 di-iodotyrosine was prepared by

Wheeler and Jamieson2. Tri-iodothyronine, in plasma and thyroid, was

recognized in 1952 by Gross and Pitt-Rivers. The big success came in 1914

when Edward Kendall isolated an iodine-containing crystalline product from

alkaline hydrolyses of thyroid tissues and named it “thyroxine”. He described it as

a “stirring activator of metabolism and probably the hormone of the thyroid”. By

then, the active principle of the thyroid gland had been identified and then

synthesized in 1927 by Charles Harrington and George Barger.

HYPOTHALAMUS, PITUITARY AND THYROID: The association between

the pituitary gland and endocrine disease was first recognized by Pierre Marie in

1890, Thyroid-stimulating hormone (TSH), was identified, by Collip and

Anderson in 1935. In 1938 it was first suggested that the engineering concept of

“feedback control” could be applied to biological systems. Soon after, this was

applied by Hoskins in endocrinology, who coined the term “thyrostat”. The phrase

“pituitary–thyroid axis” was first used in the 1940s to describe the relationship of

the two glands. In 1955 Saffran, Schally and Benfey postulated that first-order

hormones interacted in the hypothalamus to regulate the secretion of the pituitary

hormones and they coined the term “releasing factors” for these hormones.

Hypothyroidism 6

Historical aspects SIMPLE GOITRE AND CRETINISM: Descriptions of goitre have been found

in sushruta samhita by the name Galaganda, as two encapsulated swellings in the

anterior region of the neck. The Chinese used burnt sponge and seaweed in the

treatment of goitre1. Hippocrates was aware of goitre. In the Middle Ages goitre

was mentioned in the book Lives of saints and around this time, the word “goitre”

was coined1.

The presence of goitre was considered a sign of beauty in some

societies. Also, the high prevalence of goitre in adults made it difficult to associate

it with disease. Only from the work of Caleb Parry and Giuseppe Flajani at the

beginning of the 19th century was goitre recognized as a source of pathological

effects. Chatin in 1853 in France was the first to describe the correlation between

the iodine content of water, soil and air and the prevalence of goitre. This

information was neglected until confirmed in 1923 by Von Fellenverg in

Switzerland and Orr in England1. But the question was raised whether iodine

deficiency was the only cause for goitre. Robert McCarrison hypothesized the

presence of “goitrogens” that inhibit thyroid function in the drinking water as a

cause of goitre. In 1928 Chesney and his co-workers were the first to observe that

cabbage may contain goitrogens and cause goitre in rabbits (originally they were

working on syphilis research and were using cabbage-fed rabbits). During the next

decade a large number of vegetables were found to be goitrogenic e.g.

cauliflowers, turnip and Brussels sprouts. Burnt sponge and seaweed have been

used in the treatment of goitre since the 12th century.

After extensive work with these materials, the chemist Bernard

Courtois in France extracted a substance in 18121. This was examined by

Humphry Davy, then at Paris who named it iodine. The first genuine therapeutic

trial to use iodine was made by Jean-Francois Coindet of Geneva in 1820. The

Hypothyroidism 7

Historical aspects use of iodine to prevent goitre was established in 1909–13 when Marine and

Lenhart, in the USA, demonstrated the role of iodine deficiency in causing goitre

in black trout and other animals. The surgical treatment of goitre was probably

first attempted by Albucasis, a prominent Arab surgeon in the Middle Ages. The

first surgeon who achieved successful results with thyroidectomy was Theodor

Billroth at Vienna in 1849. But the techniques of this operation were highly

improved by Theodor Kocher at Berne1. He was awarded the Noble prize in 1909

for pathology and surgery of thyroid disease, the first surgeon to win the prize.

HYPOTHYROIDISM

Up to 1850 doctors were familiar with the syndrome of cretinism but

only in that year was the occurrence of features similar to cretinism in adults (i.e.

myxodema) first reported by Thomas Blizzard Curling. William Gull a

prominent pathologist gave a complete description of myxoedema in 1873,

describing five cases of cretinism in adult women. But it was William Ord who in

1878 coined the term “myxoedema” when he found extensive deposits of mucin in

the skin of feet of his patients at autopsy. In 1882, Reverdin noted the occurrence

of symptoms of myxoedema after thyroidectomy. Around the same time, Victor

Horsley produced artificial myxoedema in dogs after thyroidectomy2. Felix

Semon put an end to this controversy by stating that myxoedema and cachexia

struamiprivia were one disease and, together with cretinism, were due to one

cause: loss of thyroid function2. Semon’s statement was investigated and

confirmed by a committee appointed by the Clinical Society of London (included,

among others, Victor Horsley and Moritz Schiff). The road was now paved to

propose a suitable treatment for hypothyroidism. George Murray in 1891 and

Howitz in 1892 tried to treat myxoedema with injection of thyroid extracts with

successful results. One of Murray’s patients lived for a further 28 years after he

was treated with hypodermic injections of glycerine extract of sheep thyroid tissue

Hypothyroidism 8

Historical aspects for 6 months. At the same time, Hector Mackenzie was successful in giving

patients fresh thyroid extract by mouth. But most patients had to wait until

thyroxine was isolated and then synthesized 35 years later. Riedel in 1896

described a chronic non-malignant involvement of the thyroid gland (chronic

thyroiditis). In 1912, Hashimoto first described the disease that now bears his

name. The first evidence of a possible role for autoimmunity in thyroid disease

was the tendency of Hashimoto disease to pass sooner or later into hypothyroidism

or even an early phase of thyrotoxicosis. In 1936 a third variety of thyroiditis

(subacute and non-suppurative) was described by De Quervain and now bears his

name.

Hypothyroidism 9

Shareera

SHAREERA

The term endocrine (Greek, Endon- within, Crinen- to set apart)

was coined by Starling to contrast the actions of hormones secreted internally but

the real Father of endocrinology was French physiologist Claude Bernard

introduced the term ‘’internal secretions’’. Hormones are named from the Greek

word hormo, meaning ‘’to urge or excite’’ because they were first discovered to

play a role in hunger, sex, fight or flight response and many other basic drives.

Hormones serve within the body as invaluable messengers, governors of

development, and regulators of metabolism. 2

The classical endocrine glands Pituitary, Thyroid, Parathyroid,

Pancreatic islets, Adrenals, and Gonads communicate broadly with other organs

through the nervous system, hormones, cytokinines, and growth factors and

immune system of the body. 3

The thyroid gland is one of the largest endocrine glands in the

body. It is situated in the lower part of the neck, anterior to the trachea. It is highly

vascular and soft in consistency. It controls metabolism by producing hormones

called thyroxine (T4) and triiodothyronine (T3). Levels of these hormones

influence heart rate, body temperature, alertness, mood and many other functions.

The thyroid is controlled by the pituitary gland; located deep within the brain. No

organ packs so much critical function into so little space as the pituitary. Hence it

is described as the ‘’leader of endocrine orchestra’’. The Hypothalamus controls

almost all secretions of the pituitary.

ANATOMY OF THE THYROID GLAND

The anatomy of the thyroid gland was first described by the

famous Greek doctor Galen in the first century. He suggested that it functioned to

Hypothyroidism 10

Shareera

lubricate the larynx. Wharton in 1656 suggested that the purpose of the gland to

was to beautify the neck by giving it a rounded contour through filling the vacant

spaces around the larynx.3

DEVELOPMENT:6 The thyroid development commences at 24th day as a

midline thickening and then as an outpouching of the endodermal floor of the

pharyngeal cavity. This primordium of the thyroid eventually forms a sac like

diverticulum between the first and second pharyngeal pouches. By the sixth to

seventh week it is clearly bilobed and as the embryo the tongue grows forward,

the thyroid descends in the neck but remains attached to its point of origin by a

narrow canal, the thyroglossal duct. During the fifth and sixth weeks of

development, the distal ends of the third and fourth paired pharyngeal pouches

differentiate into the primordia of the four para thyroid glands. The neural crest

derivatives from the ultimobronchial body gives rise to thyroid medulllary c cells

that produce calcitonin, a calcium lowering hormone.The thymus is derived from

the cells that arise from the ventral portion of the third pharyngeal pouch and

migrate caudally with the thyroid and parathyroids. If the parathyroids or the

ultimobronchial bodies do not become attached to or incorporated into the thyroid,

they form ectopic glands.

Normally the thyroglossal duct ruptures and the cells atrophy or are

absorbed by the second month, leaving only a small dimple (foramen caecum) at

the junction of the middle and posterior third of the tongue; persistent thyroglossal

duct tissue may give rise to cysts. Cells in the lower portion of the duct

differentiate into thyroid thyroid tissue, forming the pyramidal lobe of the gland as

an upward, finger like extension. By the seventh week of development, when

connection of the human thyroid to the pharynx is lost, the cells of the thyroid are

grouped into clusters. At about 11weeks, a central lumen appears in each cluster,

completely surrounded by a single layer of cells. Although the thyroid is

functionally capable of trapping iodide and releasing hormone at this stage, it does

Hypothyroidism 11

Shareera

not actually respond to pituitary secretion of thyrotrophin until this occurs at

around 22nd week.

ANATOMICAL POSITION 3,4,5

The thyroid gland is located in the neck, anterior to the trachea,

between the Cricoid cartilage and the Suprasternal notch. It lies deep to the

Sternothyroid and Sternohyoid muscles from the level of fifth cervical to the first

thoracic vertebrae. An isthmus unites the lobes over the trachea usually anterior to

the 2nd and 3rd tracheal rings. It is ensheathed by the pretracheal layer of the deep

cervical fascia. So it is a well-known clinical sign that thyroid moves upward on

swallowing.

The thyroid gland consists of two lateral lobes, each lobe is about 5

cm. long; its greatest width is about 3 cm, and its thickness about 2 cm, joined by a

narrow isthmus. A conical pyramidal lobe often ascends from the isthmus or the

adjacent part of either lobe (more often the left) toward the hyoid bone, to which it

may be attached by a fibrous or fibromuscular band, the levator of the thyroid

gland.

Its weight is somewhat variable, but is usually about 30 grams, and

has a bow tie shape. It is usually smaller in regions of the world where supplies of

dietary iodine are abundant. It is nearly always asymmetric, and is usually larger

in the women than men, and it enlarges during puberty, in pregnancy, during

lactation and in the latter part of the menstrual cycle; seasonal changes have also

been reported between summer and winter, during which period a decrease in

thyroid mass frequently occurs.

Four parathyroid glands are located in the posterior region of the

thyroid. The recurrent laryngeal nerves traverse the lateral borders of the thyroid

gland and must be identified during thyroid surgery to avoid vocal cord paralysis

Hypothyroidism 12

Shareera

HISTOLOGY OF THE THYROID7

Microscopically the thyroid gland consists of follicles or vesicles

lined by cuboidal epithelium. Under the appropriate stimulation of the TSH the

low cuboidal epithelium may be converted into tall columnar epithelium.

Epithelial cells are of 2 types: Principal Cells (i.e. follicular) and Parafollicular

Cells (ie, C, clear, light cells). Principal cells are responsible for formation of the

colloid (iodothyroglobulin), whereas parafollicular cells produce the hormone

calcitonin, a protein central to calcium homeostasis. Parafollicular cells lie

adjacent to the follicles within the basal lamina. The interior of the follicle is filled

with colloid, a protenaceous material containing principally Thyroglobulin, which

is the main storage form of thyroid hormone. In addition a lesser number of

mitochondrial rich high cuboidal cells are also present between the follicular cells

are the parafollicular cells, containing particular Fluorogenicamines and high

concentration of alpha Glycerophosphate dehydrogenase and synthesize a

hormone Thyrocalitonin which reduces the calcium level of blood.

VESSELS OF THE THYROID GLAND 4

ARTERIES: The thyroid has a very rich bloodsupply and its estimated blood

flow of 4-6ml/g/min exceeds even that of the kidney. The arteries supplying the

thyroid gland are the Superior Thyroid Artery which is the first branch of the

external carotid and Inferior Thyroid artery which is the branch of subclavian

artery. The Thyroid Ima is a single vessel, which originates, when present, from

the aortic arch or the innominate artery and enters the thyroid gland at the inferior

border of the isthmus.

VEINS: Three pairs of thyroid veins the superior thyroid veins drain the superior

poles of the thyroid gland, the middle thyroid veins drain the middle of the lobes,

and the inferior thyroid veins drain the inferior poles. The superior and middle

Hypothyroidism 13

Shareera

thyroid veins drain into the IJV’s and the inferior thyroid veins drains into the

Brachiocephalic Veins posterior to the manubrium of the sternum.

LYMPHATIC DRAINAGE: It has a large lymphatic drainage through which

part of the stored Thyroglobulin may enter the circulation. Lymphatic vessels of

the thyroid gland run in the interlobar connective tissue, often around the arteries,

and communicate with a capsular network of lymphatic vessels. From here the

vessels pass into prelaryngeal, pretracheal and para tracheal lymph nodes.

Laterally, lymphatic vessels located along the superior thyroid veins pass to the

inferior deep cervical lymph nodes. Some lymphatic vessels may drain into the

brachiocephalic lymph nodes or into the thoracic duct.

NERVESUPPLY: Principal innervation of the thyroid gland derives from the

autonomic nervous system. Parasympathetic fibers come from the vagus nerves,

and sympathetic fibers are distributed from the superior, middle, and inferior

ganglia of the sympathetic trunk. These small nerves enter the gland along with

the blood vessels. Autonomic nervous regulation of the glandular secretion is not

clearly understood, but most of the effect is postulated to be on blood vessels,

hence the perfusion rates of the glands.

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THYROID HORMONE SYNTHSESIS, METABOLISM & ACTION

The syntheses of thyroid hormones are controlled at 3 different

levels. 1. at the level of hypothalamus, by modifying TRH secretion; 2. At the

pituitary level, by inhibition or stimulation of TSH secretion, and 3. At the level

of thyroid

HYPO THALAMO-PITUTORY AXIS 8

Thyroid hormone synthesis is controlled by both hypothalamic and

pituitary TSH secretion in a classic negative feed back loop. Low levels of T3 and

T4stimulates the release of TSH and TRH. TSH stimulates the thyroid to

synthesize T3and T4. When T3and T4 levels rise sufficiently, the release of TSH

and TRH is suppressed.

TRH is a tripeptide pyroglutamil-histidyl-prolineamide, synthesized

by neurons in the supra optic and supra ventricular nuclei of the hypothalamus. It

is stored in the median eminence of the hypothalamus and then transported via

pituitary portal venous system down the pituitary stalk to the anterior pituitary

gland, where it controls synthesis and release of TSH and Prolactin.

TRH stimulated TSH secretion occurs in a pulsatile fashion

throughout the 24hrs. Normal subjects will have mean TSH pulse amplitude of

about 0.6uU/mL and an average frequency of one pulse every 1.8hrs. In addition

normal subjects show a circadian rhythm, with a peak serum TSH at night,

usually between midnight 4AM. In hypothyroid patients the amplitude and the

nocturnal surges are much larger than normal. TRH secretion is stimulated by

decreased serum t4 or t3, alpha adrenergic agonists, and by arginine vasopressin.

Conversely, TRH secretion is inhibited by increased serum t4 or t3 and alpha

adrenergic blockade.

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THYROID HORMONE SYNTHESIS 8,9

Thyroid hormones are derived from Thyroglobulin, a precursor of all

thyroid hormones. It is a large glycoprotein molecule containing 5496 amino

acids, 140 tyrosil residues and about 10% carbohydrate in the form of mannose.

The iodotyrosine residues are iodinated and coupled to form the active thyroid

hormones. TG is synthesized on the rough ER of the follicular cells and the

glycosylation occurs in the Golgi apparatus.

1. Iodide transport: As iodine is a trace element, an effective mechanism is

present for the selectively trapping iodide in the thyroid follicular cells. Iodine is

taken up as an inorganic iodide; this active transport system referred to as the

iodide trap. Iodide uptake by thyroid cells is dependent on membrane ATPase.

The protein responsible for iodide transport, the so-called Sodium/Iodide

symporter or NIS, is located at the basolateral plasma membrane of thyrocytes.

Two potential iodide transporters have been proposed: PENDRIN and the recently

characterized protein named AIT for Apical Iodide Transporter.

2. Oxidation of iodide: Once within the follicular cell, the iodide is oxidized into

an active intermediate. Thyroperoxidase(TPO) oxidizes iodide in the presence of

H2O2.

3. Organification (Iodination): The attachment of iodine to tyrosyl residues in

Tg produce MIT and DIT Mon iodo tyrosine and Di iodo tyrosine residues in the

TG molecule.This process occurs at the apical plasma membrane-follicle lumen

boundary and involves H2O2, iodide, TPO, and glycosylated Tg. All rendezvous at

the apical membrane to achieve Tg iodination.The molecule has about 132 tyrosyl

residues among its two identical chains; at most, only about 1/3 of the tyrosyls are

iodinated.

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4. Coupling: The final step in hormone synthesis is the coupling of two

consenting iodotyrosyl residues to form iodothyronine.Two DIT form T4; one DIT

and one MIT form T3. Coupling takes place while both acceptor and donor

iodotyrosyl are in peptide linkage within the Tg molecule.The reaction is catalyzed

by TPO, required H2O2 and is stringently dependent on Tg structure.

5. Storage: The thyroid hormones are stored as a part of the TG molecule in the

lumen of the follicle. This TG is referred to as colloid.

Secretion: When thyroid hormone is needed, Tg is internalized at the apical pole

of thyrocytes, conveyed to endosomes and lysosomes and digested by proteases,

particularly the endopeptidases cathepsins B, L, D and exopeptidases. After Tg

digestion, T4 and T3 are released into the circulation. Nonhormonal iodine, about

70% of Tg iodine, is retrieved intrathyroidally by an iodotyrosine deiodinase and

made available for recycling within the gland.

THYROID HORMONE TRANSPORT 8

The thyroid hormones, thyroxine and Triiodothyronine (T3)

circulate in blood by reversibly binding to carrier proteins. The functions of

serum binding proteins are to 1) increase the pool of circulating hormones, 2)

delay hormone clearance and, 3) modulate hormone delivery to selected tissue

sites. Although only 0.3% or less of T3 and T4 circulates unbound, it is this free

hormone fraction that is metabolically active at the tissue and cellular level. There

are 3 major thyroid hormone transport proteins, 1. Thyroxine binding globulin

(TBG) has high affinity for thyroid hormones and carries about 80% of the bound

hormones. 2. Transthyretin (TTR, formerly known as TBPA) carries about 10%

of T4 but little T3. 3. Albumin (HSA, human serum albumin) has relatively low

affinity and binds up to 10% of T4 and 30% of T3.

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KINETICS OF THYROID HORMONES:

T4 T3 rT3

Serum levels Total, ug/dL(nmol) 8 (103) 0.12 (1.84) 0.04 (0.51)

Free, ng/dL(nmol) 1.5 (19) 0.28 (4.3) 0.24 (3.69)

Body pool ug(nmol) 800(1023) 46 (70.7) 40 (61.5)

Production rate ug/day 90 32 -

Relative metabolic potency 0.3 1 0

Half-life in plasma(t1/2) (days) 7 1 0.2

Metabolic clearance rate(MCR)L/d

1 22 90

METABOLISM OF THYROID HORMONES 8

1. Predominant pathway for Thyroid hormone metabolism is

progressive deiodination. Most plasma pool of T3 is produced from peripheral

metabolism of T4 by the deiodinase enzymes. Deiodination of the outer ring of T4

produces T3, on the other hand deiodination of the inner ring of T4 produces

reverse T3 (rT3), which is metabolically inert. Triodothyronines can be

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HISTOLOGY OF THYROID GLAND

THYROID HORMONE SYNTHESIS

ANATOMY OF THYROID GLAND

STRUCTURE OF THE THYROID HORMONES

ANATOMY OF THYROID GLAND

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progressively deiodinised to T2, T1, and T0, none of these show any biologic

activity. 2. Conjugation with sulfate or glucuronate and secretion in the bile.

3. Alanine side chains of the T4 and T3 under goes oxidative deamination and

transamination to form tetraiodo thyroacetic acid (TETRAC) and tri iodo

thyroacetic acid (TRIAC). This transmitter formation appears to be the mode of

renal metabolism of thyroid homones. 4. Decorboxylation gives rise to amine

derivatives T3 amine and T4 amine.

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ROLE OF IODINE 10

Iodine is the essential raw material for the synthesis of thyroid

hormones. Iodine is an indispensable component of the thyroid hormones,

comprising 65% of T4's weight, and 58% of T3's. The thyroid hormones are the

only iodine-containing compounds with established physiologic significance. Too

little of iodine causes mental retardation, goiter, hypothyroidism, and other

features of the so-called iodine deficiency disorders. Too much iodine increases

the incidence of iodine-induced hyperthyroidism especially multinodular goiters,

autoimmune thyroid disease and perhaps thyroid cancer.

Iodine deficiency is now recognized as a global problem with large

populations at risk who are living in an environment where the soil has been

deprived of iodine. The mountainous regions of Europe, the Northern Indian

Subcontinent, Ganges Valley in India, the extensive mountain ranges of China, the

Andean region in South America and the lesser ranges of Africa are all iodine

deficient. Some countries have areas with very high iodine intake, from dietary

custom (e.g., seaweeds in Japan) or rich soil and water (e.g., a few places in

China). The burden of iodine deficiency disorders (IDD) in India is of major

proportions. Approximately 150 million people are at risk of IDD, of whom 54

million have goiter, 2.2 million are cretins, and 6.6 million have milder neurologic

deficits. Small surveys conducted over the past two decades have identified IDD

in 24 of the 25 states. The National Goiter Control Program was launched in 1962

with iodization of salt as its primary strategy for control of IDD.

The effects of iodine deficiency on growth and development can be

considered at the various stages of life as follows,

1. Iodine deficiency in the fetus--Pathogenesis of mental retardation: Iodine

deficiency in the fetus is the result of iodine deficiency in the mother. An

insufficient supply of thyroid hormones to the developing brain may result in

mental retardation. Thyroid hormone action is exerted through the binding of T3

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to nuclear receptors which regulate the expression of specific genes in different

brain regions following a precise developing schedule during fetal and early

postnatal life.

Brain growth is characterized by two periods of maximal growth

velocity. The first one occurs during the first and second trimesters between the

third and the fifth months of gestation. This phase corresponds to neuronal

multiplication, migration and organization. The second phase takes place from the

third trimester onwards up to the second and third years postnatally. It

corresponds to glial cell multiplication, migration and myelisation. The first phase

occurs before fetal thyroid has reached its functional capacity. It is now largely

agreed that during this phase, the supply of thyroid hormones to the growing fetus

is almost exclusively of maternal origin while during the second phase, the

supply of thyroid hormones to the fetus is essentially of fetal origin.

In humans, T4 can be found in the first trimester coelomic fluid from

6 weeks of gestational age, long time before the onset of secretion of T4 by the

fetal thyroid, which occurs at the 24th week of gestation. Nuclear T3 receptors and

the amount of T3 bound to these receptors increase about six to tenfold between

10 and 16 weeks, also before the secretion of hormones by the fetal thyroid.

2. Iodine deficiency in the neonate: The brain of the human infant at birth has

only reached about one third of its full size and continues to grow rapidly until the

end of the second year. The thyroid hormone, dependent on an adequate supply of

iodine, is essential for normal brain. The apparent thyroidal iodine turnover rate

was much higher in young infants than in adults and decreased progressively with

age. In order to provide the normal rate of T4 secretion, the turnover rate for

intrathyroidal iodine must be 25-30 times higher in young infants than in

adolescents and adults Iodine deficiency also causes an increased uptake of the

radioiodide, resulting from exposure to nuclear radiation.

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3. Iodine deficiency in the child: Abnormalities in the psychoneuromotor and

intellectual development of children and adults were observed.

4. Iodine deficiency in the adult: Reduced mental function due to

hypothyroidism effects on their capacity for initiative and decision-making were

noted. In addition to this impact to brain and neuro intellectual development,

iodine deficiency at any period in life, including during adulthood, can induce the

development of goiter with mechanical complications and/or thyroid insufficiency.

AVAILABILITY OF IODINE

SOME COMMON SOURCES OF IODINE IN ADULTS

Dietary iodine Daily intake (µg) 1. Dairy products 52 2. Grains 78 3. Meat 31 4. Mixed dishes 26 5. Vegetables 20 6. Desserts 20 7. Eggs 10 8. Iodized salt 380 Other iodine sources (µg) 1. Vitamin/mineral prep (per tablet) 150 2. Amiodarone (per tablet) 75,000 3. Povidone iodine (per mL) 10,000 4. Ipodate (per capsule) 308,000

The recommended daily intake of Iodine is 150ug/day for adults, 90-

120ug/d for children, and 200ug/d in pregnant women. Breast milk contains large

amounts of iodide, mainly during the first 24 hours after ingestion.

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PHYSIOLOGICAL ACTIONS OF THYROID HORMONES 6,7,8,9

The major function of thyroxine is to control the rate of metabolism.

Cells in the body take their "cue" from thyroxine. The amount of stimulation the

cells receive from thyroxine will determine how "quickly" they perform their

functions.

Essentially all the cells in the body are target cells of thyroid

hormones. The major function of the thyroid hormones is to stimulate the

synthesis of protein once they have entered the cell nucleus. Another important

function is to stimulate the activity of the cell's mitochondria. These intracellular

organelles are the sites at which there is a controlled exchange of energy. Some

energy is conserved for the body's functioning’s, while the remainder is dissipated

as heat. The proportion of energy devoted to each of these processes is controlled

by the thyroid hormones.

Cells respond to thyroid hormone with an increase in metabolic

activity. Metabolic activity, or metabolism, is a term used to describe the

processes in the body that produce energy and the chemical substances necessary

for cells to grow, divide to form new cells, and perform other vital functions.

If we think of each cell in the body as a motor car, then thyroid

hormone acts as if tapping on the accelerator pedal. Its message is "go."

1. Metabolism:

Thyroid hormones stimulate diverse metabolic activities most tissues,

leading to an increase in Basal Metabolic Rate. Each mg raises BMR to about

1000C. One consequence of this activity is to increase body heat production,

which seems to result, at least in part, from increased oxygen consumption and

rates of ATP hydrolysis. By way of analogy, the action of thyroid hormones is

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akin to blowing on a smoldering fire. A few examples of specific metabolic effects

of thyroid hormones include

a) Lipid metabolism: Increased thyroid hormone levels stimulate fat mobilization,

leading to increased concentrations of fatty acids in plasma. Plasma concentrations

of cholesterol and triglycerides are inversely correlated with thyroid hormone

levels.

b) Carbohydrate metabolism: Thyroid Hormone’s increase the rate of GI tract

absorption of glucose and enhancement of insulin-dependent entry of glucose into

cells and increased gluconeogenesis and glycogenolysis to generate free glucose

c) Protein metabolism: Thyroid Hormone’s increase cellular uptake of amino

acids and incorporation of these amino acids into proteins.

2. Cardiovascular system: Thyroid hormones increases heart rate, cardiac

contractility and cardiac output and also have effects on myocardium. They also

promote vasodilatation, which leads to enhanced blood flow to many organs.

3. Central nervous system: They regulate neuronal proliferation and

differentiation, myelogenesis, neuronal outgrowth and synapse formation. Too

little thyroid hormone and the individual tend to feel mentally sluggish, while too

much induces anxiety and nervousness.

4. Actions on skeletal muscles: Thyroid Hormone’s have direct action on muscle.

They increase both the content of the plasma lemma electrogenic Na-K pump and

increase the resting membrane potential. They also increase the rate and amount of

calcium uptake in the sarcoplasmic reticulum, there by increasing calcium

availability on stimulation. They influence the isotope availability of myosin and

increase myosin ATP ase activity. Thyroid Hormone’s stimulate increased bone

turnover, increasing bone resorption and to a lesser degree bone formation.

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5. Kidneys: Thyroid Hormone’s 1. increases Nitrogen excretion, 2. increases urine

volume by raising the general metabolism and thus increasing nitrogenous end

products which acts as diuretics.

6. Gastrointestinal system: Thyroid hormones stimulate gut motility.

Table 1.1showing the physiological actions of thyroid hormones on different

systems:

S.no System or Event Affected Actions of T3/T4

1 Basal Metabolism

Increases basal metabolic rate. Increases body temp (calorigenesis). Increases appetite.

2 Carbohydrate, lipid & protein

Metabolism

Promotes glucose catabolism for energy. Stimulates protein synthesis. Increases lipolysis. Enhances cholesterol excretion in bile.

3 Heart Promotes normal cardiac function.

4 Nervous System Promotes normal neuronal development in fetus and infant. Promotes normal neuronal function in adult. Enhances effects of sympathetic nervous system.

5 Musculoskeletal Promotes normal body growth and maturation of skeleton. Promotes normal function and development of muscles.

6 Reproductive Promotes normal female reproductive ability and lactation.

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NIDANA 6,7,10,11

Hypothyroidism results from inadequate production of thyroid

hormone. Any structural or functional defects of thyroid gland that significantly

impairs its output of hormones will lead to the hypo metabolic state of

hypothyroidism.

Hypothyroidism may be classified as

1. Primary (thyroid failure),

Hypothyroidism caused by the inability of the thyroid gland to make

T3 and T4 is called primary hypothyroidism.

2. Secondary (due to pituitary TSH deficit), and 3. Tertiary (due to hypothalamic

deficiency of TRH)

Since the thyroid gland is regulated by the pituitary gland and

hypothalamus, disorders of these organs can cause the thyroid gland to produce

too little thyroid hormone as well. This condition is called secondary

hypothyroidism.

4. Peripheral resistance to the action of thyroid hormones.

1. PRIMARY: Primary hypothyroidism is a condition of decreased hormone

production by the thyroid gland. It accounts for 95 per cent of hypothyroidism

cases, and only 5 per cent or less are suprathyroid in origin. The most common

cause of primary hypothyroidism is

i). iodine deficiency ii). AITD’s. iii). Drugs; iv). Iatrogenic; v). Congenital

Transient hypothyroid includes silent and part partum thyroiditis.

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1. IODINE DEFICIENCY: iodine very essential for the production of TSH.

When dietary iodine intake is inadequate for thyroid hormone synthesis, the serum

T4 level initially falls and a number of processes ensue to restore adequate thyroid

hormone production. The pituitary gland senses low levels of circulating T4 and

releases more TSH.

2. DRUGS: Certain drugs can block hormone synthesis produce Hypothyroidism.

The most important drugs causing hypothyroidism are: lithium carbonate, para-

amino salicyclic acid, amiodarone, sulfonamides and phenylbutazona.

3. AITD’s: The body recognizes the thyroid antigens as foreign, and a chronic

immune reaction ensues, resulting in lymphocytic infiltration of the gland and

progressive destruction of functional thyroid tissue. Up to 95% of affected

individuals have circulating antibodies to thyroid tissue. Antimicrosomal or

antithyroid peroxidase (anti-TPO) antibodies are found more commonly than

antithyroglobulin antibodies (95% vs 60%). These antibodies may not be present

early in the disease process and usually disappear over time.

In situations where the immune system no longer treats tissues of

the host as normal conditions of the body but reacts against them as it works

against a foreign tissue the ensuing disease is known as autoimmune disorders.

Thyroid autoimmune diseases are a group of autoimmune disorders, which are

characterized by circulating antibodies and lymphocytes infiltration of their tissues

of particular organs.

4. IATROGENIC: The most common cause of hypothyroidism is destruction of

the thyroid gland by disease or as a consequence of vigorous ablative therapies to

control thyrotoxicosis.

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5. SURGERY AND RADIATION: It is an important cause of hypothyroidism in

patients who undergo Total or subtotal thyroidectomy for Graves' disease or

multinodular goiter. External irradiation (for head and neck neoplasms, breast

cancer, or Hodgkin disease) and Postradioactive iodine (I-131) therapy for

hyperthyroidism may result in hypothyroidism.

Infiltrative diseases of the thyroid: Progressive systemic sclerosis (scleroderma)

can cause hypothyroidism from immune and non-immune mechanisms. The non-

immune mechanism is due to severe fibrosis involving the thyroid gland. These

conditions may also cause central (secondary) hypothyroidism from pituitary

infiltration. Hypothyroidism due to sarcoidosis is rare.

2. SECONDARY HYPOTHYROIDISM: In adults, it is almost always due to

pituitary disease. These patients often have other associated pituitary dysfunction.

It may also be seen due to autoimmunity against thyrotrophs (cells that produce

TSH).

3. TERTIARY HYPOTHYROIDISM: is due to hypothalamic diseases like

sarcoidosis, tumours etc.

4. THYROID HORMONE RESISTANCE SYNDROME

In this condition, there is a decrease in sensitivity of peripheral tissue receptors to

thyroid hormones.

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SAMPRAPTI 12

Hypothyroidism is a clinical syndrome resulting from a deficiency of

thyroid hormones which in turn results in a generalized slowing down of

metabolic process.

The clinical manifestations of the hormone lack depend on the age

when it first appears. It is seen in 3 groups of patients, in the new born termed as

cretinism or congenital hypothyroidism, in the childhood or adolescence known as

juvenile hypothyroidism, in the adult usually termed as myxedema.

CONGENITAL HYPOTHYROIDISM 12, 15

In the newborn it is known as congenital hypothyroidism,

previously called as cretinism. The French term meaning ‘’ Christ like’’ and was

applied to those unfortunates because they were considered to be incapable of

sinning.10

The most common causes are agenesis and dysgenesis.

Ectopic thyroid gland: Hypothyroidism may result from failure of thyroid gland to

descend during embryonic development from its origin at the base of the tongue

do its usual size in the lower anterior neck which results in ectopic thyroid gland

that functions poorly.

Placental transfer to the embryo TSH- RAb( block) from a mother

with hashinoto’s thyroiditis may result in agenesis of thyroid gland and

“athyreotic cretinism”.

Rare causes include administration of iodides, antithyroid drugs or radioactive

iodine for thyrotoxocosis.

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The symptoms of congenital hypothyroidism include jaundice poor

feeding, hoarse cry, umbilical hernia, constipation, somnolence, delay in reaching

normal mile stones of development, short stature coarse features with protruding

tongue, broad flat nose, widely set eyes, impaired mental development and marked

retardation of none maturation. Absence of proximal tibial and distal femoral

epiphysis strongly suggests congenital hypothyroidism.

Since the disorder causes severe mental retardation, unless promptly

treated, since it is not always possible to make a clinical diagnosis at birth,

universal screening of; all neonates is now common in many countries like US and

UK. This is normally based on TSH assay of heel prick or cord blood. 11,12

Pendred’s syndrome16: Pendred’s syndrome is caused by a genetic defect that

limits the incorporation of iodine into thyroid hormone, which wrecks the structure

of the hormone it is characterized by overt or sub clinical hypothyroidism, goiter

and mild to moderate sensorineural hearing impairment.

JUVENILE HYPOTHYROIDISM 13

Atrophy of the gland or defective function of thyroid gland,

thyroiditis, and secondary pituitary deficiency are the common causes. It is

characterized by dwarfism with delayed skeletal maturation, apathy physical and

mental torpor, constipation slow teething, and large tongue pot belly with

umbilical hernia deep voice, myxedema and delayed sexual development.

ADULT HYPOTHYROIDISM 7,18,12

It is also called as myxedema. 95%of the cases are due to primary

hypothyroidism, thyroid gland malfunction either by structural or functional

impairment. The main causes are,

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IODINE DEFICIENCY14 :

The main causes of primary hypothyroidism which may be attribute

to dietary factors or to inefficient iodine conservation due to intra thyroid and

peripheral tissue deiodinase enzyme deficiency is the main cause for

hypothyroidism. Impaired transport of iodine, deficient peroxidase with impaired

oxidation of iodinate into iodine and failure to incorporate, impaired coupling of

iodinated tyrosines to T3 and T4 these all cause impaired production of thyroid

hormones presumably results in increased TSH production and consequently in

hypothyroidism.

AUTOIMMUNE THYROID DISORDERS 17, 12

Immunologic defense against foreign substances involves

macrophages that ingest and digest the foreign material and present peptide

fragments on the cell surface in association with a class II protein coded by the

HLA-DR region of the MHC gene complex. This complex is recognized by a

T cell receptor on a CD 4 helper T cell, which stimulates the release of cytokines

such as interleukin-2(IL-2).these cytokines amplify the response by inducing

T cell activation and division, induction of killer cell activity in CD8 suppressor

cells, and stimulation of antibody formation against the foreign antigen by B

lymphocytes. Eventually the activation process is muted by the activation of CD8

suppressor cells.

There are three major thyroidal auto antigens: thyroglobulin (Tg),

thyroxyperoxidase (TPO) and the TSH receptor (TSH-R) auto antibodies to these

antigens are useful markers for the presence of auto immune thyroid diseases.

HASHIMOTO’S THYROIDITIS 12,22

Characterized by the destruction of thyroid cells by various cells

and antibody mediated immune processes. It is a histologic diagnosis first

described by Hakaru Hashimoto, a Japanese surgeon.

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Genetic factors most likely play some role in autoimmune

thyroiditis. For example, many patients with Hashimoto's thyroiditis express a

gene called the Fas gene, which interacts with thyroid cells and trigger a process

called apoptosis, in which the cells begin to self-destruct. The Fas gene is linked to

genes that regulate tumor necrosis factors, which are products of the immune

system that trigger a damaging inflammatory response in cells.

In Hashimotos thyroditis TSH-R blocking immunoglobulins bind to

the receptor and block TSH function causing hypothyroidism. There is marked

lymphocytic infiltration of the thyroid with germinal centre formation, atrophy of

the thyroid follicles accompanied by oxyphyl metaplasia, absence of colloid and

mild to moderate fibrosis. In the early stages of hashimoto’s thyroditis, the thyroid

may produce too much thyroid harmone but as the thyroid is slowly destroyed the

patients thyroid harmone levels drop, at the latter stages it may become atrophic

thyroiditis.

3. IATROGENIC CAUSES12:

The most common cause of hypothyroidism is destruction of the

thyroid gland by disease or as a consequence of vigorous ablative therapies to

control thyrotoxicosis. Thyroid destruction secondary to radioactive iodine or

surgery, as treatment for hyperthyroidism can also cause hypothyroidism. Patients

who have been treated for a hyperthyroid condition (such as Graves' disease) and

received radioactive iodine may be left with little or no functioning thyroid tissue

after treatment. Similarly, removal of the thyroid gland during surgery will be

followed by hypothyroidism.

4. DRUGS18:

Certain drugs can block hormone synthesis and produce hypothyroidism.

1. Antithyroid drugs (eg, propylthiouracil, methimazole, carbimazole).

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2. Lithium inhibits thyroidal iodide transport and release of T4 and T3 and may

cause hypothyroidism.

3. Amiodarone has large iodine content, and can cause hypothyroidism by

inhibiting peripheral T4-to-T3 conversion.

4. Interferon alpha may induce thyroid autoimmunity in 10-20% of patients. It

leads to production of anti-Tg, anti-TPO, and TSH receptor-blocking antibodies.

5. Phenytoin, carbamazepine, and rifampin increase the hepatic clearance of

levothyroxine by induction of cytochrome P-450 enzymes. This can lead to an

increased levothyroxine requirement in patients on replacement therapy.

Hypothyroidism may be transient and require no or only short-term

therapy, as in patients with painless thyroiditis or postpartum thyroiditis.

5. THYROID HORMONE RESISTANCE SYNDROME 19,14

Thyroid hormone resistance has only been described in relatively

recent times. In this, there is a decrease in sensitivity of peripheral tissue receptors

to thyroid hormones. The clinical syndrome of hypothyroidism ensues, despite

excess thyroid hormones in the circulation. In contrast to this, a far rarer condition

has been described when the pituitary gland does not sense the circulating thyroid

hormones, inhibiting the feedback mechanism so that the pituitary gland continues

to secrete an excess amount of TSH, which, in turn, stimulates the thyroid gland,

producing an excess amount of T3 and T4. This is called selective pituitary

resistance and can produce hyperthyroidism. The defect lies in a mutation of the

thyroid receptor gene. About 300 families with these disorders have been

identified but the population prevalence is difficult to tell.

2. CENTRAL (SECONDARY/TERTIARY) HYPOTHYROIDISM 12,17

Pituitary or Hypothalamic disease can also lead to condition of

hypothyroidism. If for some reason the pituitary gland or the hypothalamus is

unable to signal the thyroid and instruct it to produce thyroid hormones, a

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decreased level of circulating T4 and T3 may result, even if the thyroid gland itself

is normal. If this defect is caused by pituitary disease, the condition is called

"secondary hypothyroidism." If the defect is due to hypothalamic disease, it is

called "tertiary hypothyroidism."

1. Loss of functional tissue: 1. Tumors (Pituitary adenoma, Craniopharyngioma,

Meningioma, Dysgerminoma, Glioma, Metastases), 2. Trauma(surgery,

irradiation, head injury), 3. Vascular (Ischemic necrosis, Hemorrhage, Stalk

interrruption, Aneurysm of internal carotid artery), 4. Infections (Abcess,

Tuberculosis, Syphilis, Toxoplasmosis), 5. Infiltrative (Sarcoidosis, Histiocytosis,

Hemochromatosis),6.Chronic lymphocytic hypophysitis, 7. Congenital (Pituitary

hypoplasia, Septooptic dysplasia, Basal encephalocele).

2. Functional defects in TSH biosynthesis and release: 1. Mutations in genes

encoding for TRH receptor, TSHß, or Pit-1, 2. Drugs: Dopamine;

Glucocorticoids; L-thyroxine withdrawal.

Hypothyroidism 34

Clinical features

CLINICAL FEATURES OF HYPOTHYROIDISM12, 17,18

Hypothyroid disease is one of the most underdiagnosed and mis-

diagnosed diseases as its clinical features for hypothyroidism are notorious.

Hypothyroidism doesn’t have any characteristic symptoms. There are no

symptoms that people with hypothyroidism always have and many symptoms of

hypothyroidism can occur in people with other diseases. The manifestations of

hypothyroidism are as below.

1. METABOLIC CHANGES IN HYPOTHYROIDISM:

1. Weight gain: usually only 5-10lbs, rarely a cause of morbid obesity,

decreased oxygen consumption- per unit body surface area.

2. Cold intolerance: decreased rate of heat production.

3. Hyperlipidemia(cholesterol, tryglycerides, phospholipids) – a decrease in

cholesterol synthesis with a greater decrease in its removal results in

hypercholesterolemia which predisposes to atherogenesis.

4. Hyperhomocystenemia: predisposes to increased atherogenesis.

5. Hypoglycemia: Rare, suspected in secondary hypothyroidism.

6. Effusions: Increased interstitial fluid and increased CSF protein. Increased

albumin synthesis and increased capillary permeability to albumin.

7. Growth retardation:

8. Decreased in metabolism of drugs, hormones, enzymes.

2. CUTANEOUS MANIFESTATIONS OF HYPOTHYROIDISM:

1. Dry, rough, and thick skin covered with fine superficial scales especially

prominent over elbow, knees and heels.

Hypothyroidism 35

Clinical features

2. Pale waxy, cool skin, sometimes with a yellow tint.

3. Periorbital edema: mucopolysachharide deposition with increased

osmatic effect and fluid accumulation.

4. Coarse, brittle, dull hair can’t hold wave.

5. Alopecia: involving scalp, lateral third of eyebrows or generalized (sec

hypothyroidism)

6. Brittle nails with transverse striations

7. Lack of sweating- atrophy of sweat glands.

Histological features include thinning of epidermis with

hyperkeratosis of stratum corneum which is infiltrated with

mucopolysachhaarides, hyaluronic acid and chondrantin sulfate. It is found mainly

in the papillary dermis around the blood vessels and the cutaneous appendages.

3. NEUROMUSCULAR SYSTEM OF HYPOTHYROIDISM:

1. Sensory complaints such as tingling in a stock glove distribution or

painful dysesthesias.

2. Carpal tunnel syndrome:

3. Generalized peripheral neuropathy with upper extremities

disproportionately involved.

4. Myasthenia gravis

5. Muscle stiffness, aching, myalgias, cramps, weakness and fatigue.

6. Slow muscle stretch reflex with delay in both contraction and relaxation

phases.

Hypothyroidism 36

Clinical features

7. Myoedema

8. Hoffman syndrome: Muscle enlargement with normal or reduced strength.

9. Elevation of Creatine phospokinase(CPK), the dominant iso enzyme being

MM type indicative of skeletal muscle course.

4. NEUROPSYCHIATRIC:

1. Disturbances in concentration, memory, and intellect.

2. Lack of ambition

3. Slow thought, and slow speech.

4. Depression, agitation, psychosis (myxedema madness).

5. Drowsiness, lethargy, increased need for sleep.

6. Hallucinations (late)

7. Myxedema coma (late)

5. CARDIAC SYSTEM IN HYPOTHYROIDISM:

1. Pericardial effusion-usually asymptomatic.

2. Exertional dyspnoea, fatigue, decreased exercise tolerance.

3. Pulse<81 or frank bradycardia.

4. Normal blood pressure, hypertension and sometimes hypotension.

5. Hyper cholstrelemia and hyper triglyceridemia.

6. Hyperhomocystenemia.

Hypothyroidism 37

Clinical features

7. Coronary artery disease- symptoms modified by decreased cardiac oxygen

consumption and decreased work load; therefore low frequency of angina

or infarction.

8. Ventricular septal hypertrophy

9. Cardiac dilatation

10. Congestive heart failure-uncommon in absence of underlying heart disease

and in severe hypothyroidism.

6. RESPIRATORY SYSTEM IN HYPOTHYROIDISM:

1. Pleural effusion

2. Reduced max. Breathing capacity and diffusing capacity

3. Upper airway obstruction from thyroid enlargement or elongated tongue.

4. Obstructive sleep apnea due to obstruction of upper air way and in some

cases altered respiratory drive.

5. Alveolar hypoventilation and co2 retention due to depression of both

respiratory muscles and the hypoxic and hypercapnic ventilatory drive.

6. Prolonged theophylline half life predisposing to toxicity.

7. HEMATOLOGICAL SYSTEM IN HYPOTHYROIDISM:

1. Anemia:

• Normochromic normocytic.

• Hypochromic microcytic due to iron deficiency

Hypothyroidism 38

Clinical features

• Macrocytic due to vit B12 deficiency, folate deficiency or Thyroid hormone

deficiency,

2. Bleeding: abnormal platelet function

Deficiencies of factors,- VII, VIII, IX, XI.

8. CATECHOLAMINES IN HYPOTHYROIDISM:

1. Ptosis.

2. Hypothermia: failure of cold or sepsis to increase thermo genesis due to a

lack off response to catecholamine.

3. Normal secretion and plasma epinephrine levels.

4. Elevated secretion of plasma norepinephrine levels:

5. Decreased plasma cAMP response to epinephrine.

6. Decreased B-adrenergic receptors.

7. Bradycardia.

9. GASTRO INTESTINAL SYSTEM IN HYPOTHYROIDISM:

1. Weight gain: modest but marked increase in weight almost a feature.

2. Anorexia

3. Decreased intestinal motility-

Gastroparesis, constipation, gaseous distension, paralytic ileus, megacolon,

4. Ascitis: unusual to be clinically detectable although increased fluid is

common.

Hypothyroidism 39

Clinical features

5. Autoimmune gastritis with achlorhydria and failure to absorb vitB12, and

failure to absorb vitB12.

6. Elevated transaminase levels due to delayed clearance.

10. RENAL SYSTEM AND ELECTROLYTES:

1. Fluid retention-a large extra vascular accumulation of albumin due to

enhanced vascular permeability and altered endothelial cell bodies and a

lack of compensatory increase in the flow of lymph.

2. Excessive urinary sodium loss

3. Decreased plasma volume

4. Increase in ADH.

5. Hyponatremia.

6. Increased renal vaso constriction.

7. Decrease in glomerular filtration and renal plasma flow.

8. Increase in plasma rennin angiotension II but decrease in plasma

aldosterone.

11. REPRODUCTIVE SYSTEM IN HYPOTHYROIDISM:

1. Menorrhagia or meno-metrorrhagia-anovulatry cycles, endometrial

proliferations, breakthrough bleeding.

2. Amenorrhoea in primary or secondary hypothyroidism; however there is

an increased incidence of hashimoto’s thyroiditis with turner’s syndrome.

3. Galactorrhoea seen in primary or secondary hypothyroidism.

Hypothyroidism 40

Clinical features

4. Decreased fertility and increased abortions, still births and prematurity.

5. Delayed puberty in both sexes.

6. Van Wyk-Grumbach syndrome-precoceous puberty, galctorrhea, sella

enlargement in juvenile hypothyroidism

7. Diminished libido, impotance and conflicting data regularly testicular

functions.

Hypothyroidism 41

Pathology

PATHOLOGY OF HYPOTHYROIDISM 6,18,20,21

The characteristic pathologic finding in hypothyroidism is a peculiar

mucinous nonpitting edema (myxedema), which is most obvious in the dermis but

can be present in many organs. The myxedema is due to accumulation of

hyaluronic acid and other glycosaminoglycans in interstitial tissue; these

hydrophilic molecules attract much water. The deposits of glycosaminoglycans

have been related to loss of the inhibitory effects of thyroid hormone on the

synthesis of hyaluronate, fibronectin and collagen by fibroblasts.

The skin is distinctly abnormal. There is hyperkeratotic plugging

of sweat glands and hair follicles. The dermis is edematous, and the collagen

fibers are separated, swollen, and frayed. Skeletal muscle cells are swollen and

appear grossly to be pale and edematous. Alternatively, the normal striations are

lost, and degenerative foci are seen in the cells. The heart may be dilated and

hypertrophied. Interstitial edema and an increase in fibrous tissue are present. The

individual muscle cells may show the same changes seen in skeletal muscle. The

serous cavities may all contain abnormal amounts of fluid with normal or high

protein content.

The liver may appear normal or may show evidence of edema. The

mitochondria tend to be spherical and their limiting membranes smooth, whereas

those of the liver in thyrotoxicosis vary in shape and have wrinkled outer

membrane. The skeleton may be unusually dense on radiographic examination. In

children, bone maturation is usually retarded, and typical epiphyseal dysgenesis of

hypothyroidism is present.

The brain may show atrophy of cells, gliosis, and foci of

degeneration. There is neuronal hypoplasia, retarded myelination, and decreased

vascularity.

Hypothyroidism 42

Pathology

The blood vessels often show prominent atherosclerosis. In the

intestinal tract there is an accumulation of mast cells and interstitial mucoid

material, especially near the basement membrane.

The smooth muscle cells may show lesions similar to those seen in

skeletal muscle. The mucosa of the stomach, small bowel, and large bowel may be

atrophic. The rest of the gastrointestinal tract, especially the colon, may be much

dilated (myxedema megacolon). The uterus typically has a proliferative or

atrophic endometrium in premenopausal women.

The kidney is grossly normal. Microscopic studies showed

thickening of the glomerular and tubular basement membranes, proliferation of the

endothelial and mesangial cells, intracellular inclusions, and extracellular

deposition of amorphous material with characteristics of acid

mucopolysaccharides.

Pituitary fossa enlargement and pituitary tumors are observed in

congeneatl hypothyroidism. In pituitary hypothyroidism the pituitary may be

replaced by fibrous and cystic structures, granulomas, or neoplasia. The adrenals

may be normal or their cortex may be atrophied, and is thought to be of

autoimmune etiology.

The testes may show Leydig cells with involutionary nucleus and

cytoplasm, hyalinization, or involution of the tubular cells, and proliferation of

intertubular connective tissue in hypothyroidism with onset before puberty.

Hypothyroidism 43

Sick euthyroid syndrome

SICK EUTHYROID SYNDROME ( SES)12

Several systemic illnesses can upset thyroid hormone secretion,

transport and/or metabolism. Thus, biochemical assessment of the thyroid state

can vary widely without there being an intrinsic problem with the gland. This

situation has been called sick euthyroid syndrome (SES).

A very high percentage (40-70 per cent) of patients with a non-

thyroid illness may have one or more abnormalities of the thyroid function tests.

The severity of illness is usually more important than its nature. This can be

divided into three main types - low T3 state, low T3 - T4 state and a high T4 state,

all with normal TSH. The common conditions encountered in day-to-day clinical

practice are caloric deprivation (usually secondary to systemic illness), liver

disease, poorly controlled diabetes mellitus, nephrotic syndrome, chronic renal

failure, systemic infection and psychiatric disorders. The vast majority is euthyroid

and requires no specific thyroid related therapy.

Many pharmacological agents affect the results of the thyroid

function tests, either by acting on the thyroid gland or by altering the peripheral

distribution and metabolism of the hormone. Common drugs that alter the thyroid

hormone indices are glucocorticoids, dopamine, androgens, salicylates, frusemide,

heparin, amiodarone (discussed later) and propranolol. Some of these effects can

be exploited in clinical practice, for example, the use of propranolol and

corticosteroids in thyrotoxic crisis.

Hypothyroidism 44

Investigations

INVESTIGATIONS 22,18

The function of the thyroid gland may be evaluated in many

different ways. (l) Tests of thyroid hormones in blood, (2) evaluation of the

hypothalamic pituitary thyroid axis, (3) assessment of iodine metabolism, (4)

estimation of gland size, (5) thyroid biopsy, (6) observation of the effects of

thyroid hormones on peripheral tissues and (7) measurement of thyroid auto

antibodies.

1. TESTS OF THYROID HORMONES IN BLOOD:

Thyroid hormones are transported in serum bound to carrier

proteins. The 0.04% of T4 and 0.4% of T3 that is free is the biologically active

form. Measurement of thyroid hormone levels is done as follows:

1. Serum Total Thyroxin (T4, normal value 4-12 microg/dL). This test measures

both free and bound T4. In healthy patients (without abnormalities in thyroid

binding proteins), total T4 reflects thyroid hormone activity.

2. Serum Total Triiodothyronine (T3, normal values 80-200 ng/dL). This test

measures both free and bound T3.

TBG: Thyroid Binding Globulin (TBG) is the major thyroid hormone binding

proteins. The level of TBG in the blood is not routinely measured

Free Thyroid Hormone: As the free thyroid hormone is the biologically active, it

is important that a measurement of free thyroid levels be done.

2. EVALUATION OF THE HYPOTHALAMICPITUITARY THYROID

AXIS

The TRH stimulation test is rarely needed now because of improved TSH assays.

TSH: Serum TSH is the best SCREENING test for the diagnosis of

hypothyroidism or hyperthyroidism in healthy ambulatory individuals. It is the

initial test done to assess thyroid function and the only test needed if it is normal.

Hypothyroidism 45

Investigations

However, if hypothalamic/pituitary disease is suspected or significant alterations

in binding proteins are expected, then a measure of free T4 (index or direct assay)

is needed together with TSH.In most healthy patients, TSH values are 0.5-1.5

mU/L, but reference ranges vary up to 5 mU/L.

A modern or delayed rise may be seen in patients with hypothalamic

disease and hypothyroidism. Measurement of TSH has become the most sensitive,

most convenient and most specific test for the diagnosis of both hyperthyroidism

and hypothyroidism. TSH levels also rise for a week and then fall in conditions of

non-thyroidal illness, including surgery, trauma or infection.

3. IODINE METABOLISM & BIOSYNTHETIC ACTIVITY

Radioactive iodine allows assessment of the turnover of iodine by

the thyroid in vivo. Iodine 123 is the ideal isotope for this purpose.

4. ESTIMATION OF GLAND SIZE:

THYROID IMAGING

1. Radionuclide imaging:

Radionuclide scan provide information about the size and shape of

thyroid gland and the geographic distribution of functional activity in the gland.

Functioning thyroid nodules are called ‘’hot’’ nodules and nonfunctioning ones

are called ‘’cold’’ nodules.

2. Fluorescent scanning:

The iodine content can be determined and an image of thyroid gland

can be obtained by fluorescent scanning without administration.

THYROID ULTRA SONOGRAPHY:

It is particularly useful for measuring the size of the gland or

individual nodules. It is useful for differentiating solid from cystic lesions.

Hypothyroidism 46

Investigations

THYROID MAGNETIC RESONANCE IMAGING:

MRI provides an excellent image of the thyroid gland, including

posterior or substernal extension of a goiter or malignancy.

5. THYROID BIOPSY:

Fine Needle Aspiration Biopsy: Fine-needle aspiration (FNA) biopsy is the

procedure of choice to evaluate suspicious nodules and has proved the best method

for the differentiation of benign from malignant thyroid diseases.

6. OBSERVATION OF THE EFFECTS OF THYROID HORMONES ON

PERIPHERAL TISSUES:

BMR: it is raised in hyperthyroidism and decreased in hypothyroidism.

Tendon reflexes: particularly ankle jerk and knee jerk are tested. The relaxation is

quite slow in hypothyroidism.

Serum cholesterol is usually lowered in hyperthyroidism and elevated in

hypothyroidism.

7. THYROID AUTO ANTIBODIES:

The diagnosis of autoimmune hypothyroidism is usually confirmed by the

presence of particular antibodies in the blood.

1. Thyroglobulin antibody ( Tg Ab)

2. Thyroperoxidase antibody (TPO Ab)

3. TSH receptor antibody either stimulating or inhibiting (TSH-R Ab(stim) and

TSH-R Ab(block)).

It is measured by Heamagglutination, ELISA or RIA. These tests will clarify the

cause of illness.

Hypothyroidism 47

Complications

COMPLICATIONS 13,17,20

Untreated hypothyroidism can lead to a number of health problems:

Goiter: Constant stimulation of the thyroid to release more hormones may cause

the gland to become larger — a condition known as goiter. Hashimoto's thyroiditis

is one of the most common causes of a goiter. Although generally not

uncomfortable, a large goiter can affect the appearance and may interfere with

swallowing or breathing.

Heart problems: Hypothyroidism may also be associated with an increased risk

of heart disease, primarily because high levels of low-density lipoprotein (LDL)

cholesterol — the "bad" cholesterol — can occur in people with an underactive

thyroid. Even subclinical hypothyroidism, a more benign condition than true

hypothyroidism, can cause an increase in total cholesterol levels and impair the

pumping ability of the heart. Hypothyroidism can also lead to an enlarged heart

and heart failure.

Mental health issues: Depression may occur early in hypothyroidism and may

become more severe over time. Hypothyroidism can also cause slowed mental

functioning.

Myxedema. This rare, life-threatening condition is the result of long-term,

undiagnosed hypothyroidism. Its symptoms include intense cold intolerance and

drowsiness followed by profound lethargy and unconsciousness. A myxedema

coma may be triggered by sedatives, infection or other stress on the body.

Birth defects: Babies born to women with untreated thyroid disease may have a

higher risk of birth defects than do babies born to healthy mothers. These children

are more prone to serious intellectual and developmental problems.

Infants with untreated hypothyroidism present at birth are also at risk of serious

problems with both physical and mental development.

Hypothyroidism 48

Goiter

GOITRE 23,21,16

The term goiter is derived form the French word ‘goitre’ (latin-

gutter) –means throat. We use the term goiter to denote enlargement of the thyroid

glandirrespective of its cause.

Goiter is classified as follows-

1. Simple goiter-i) diffuse hyperplastic goiter, ii)nodular goiter, iii)colloid goiter. .

2. Toxic goiter- i) diffuse toxic goiter, ii) toxic nodular goiter, iii) toxic nodule.

3. Neoplastic goiter- i) benign tumours, ii) malignant tumours.

4. Thyroiditis - i) hashimoto’s thyroiditis, ii)subaacute thyroiditis, iii) reidels

thyroiditis.

Some of them are explained below.

Simple goiter: results from TSH stimulation, which in turn results from

inadequate thyroid hormone synthesis. Iodine deficiency was the most common

cause for endemic goiter in low iodide intake areas. Iodine deficiency causes

impaired hormone synthesis and, increase in TSH secretion which induces diffuse

thyroid hyperplasia followed by development of new focal or nodular hyperplasia.

Goiter may be seen in some families; inborn errors in metabolism cause low

thyroxine levels which leads to raise in TSH production and causing hyperplasia

of the follicular cells.

Goitrogens like lithium carbonate and some vegetable food stuffs

such as goitrin, found in certain roots and seeds; and cyanogenic glycosides, found

in cassava and cabbage, that release thiocyanates which may cause goiter

particularly in the presence of iodide deficiency. Phenols, phthalates, pyridines,

Hypothyroidism 49

Goiter

and polyaromatic hydrocarbons found in industrial waste water are also

goitrogens.

If the thyroid is markedly enlarged it can cause tracheal or

esophageal compression. Substernal goiter may obstruct the thoracic inlet.

Pemberton’s sign refers to symptoms of faintness with evidence of facial

congestion and external jugular vein obstruction when the arms are raised above

the head.

Nontoxic multi nodular goiter (MNG):

Iodine deficiency, Genetic, Autoimmune and Environmental causes

influence the pathogenesis of the disease. Histology reveals hyper cellular regions

to cystic areas filled with colloid. Most nodules within the colloid are polyclonal

in origin, suggesting a hyper plastic response to locally produced growth factors

and cytokines.

MNG’s are usually extraordinarily large and develop fibrotic areas

that cause compression. Sudden pain in MNG, hoarseness reflecting laryngeal

nerve involvement suggests malignancy.

Toxic MNG:

It is similar to that of notoxic MNG but major difference being the

presence of functional autonomy in toxic MNG. The clinical presentation includes

subclinical hyperthyroidism or mild thyrotoxicosis.

Benign thyroid nodules:

These include focal areas of chronic thyroiditis, a dominant portion

of a MNG, a cyst involving thyroid tissue, para thyroid tissue, or thyroglossal duct

remnants, and agenesis of one lobe of thyroid, with hypertrophy of other lobe.

Hypothyroidism 50

Goiter

Benign neoplasms include follicular adenomas such as colloid or macrofollicular

adenomas, fetal adenomas and embryonal adenomas.

Hyper functioning solitary nodule:

It is referred to as toxic adenoma due to functional effects of

mutations that stimulate the TSH R signaling pathway.

THYROID CANCER

Radiation exposure increases the risk of malignant thyroid nodules,

which predisposes to chromosomal breaks, presumably leading to genetic

rearrangement and loss of tumor suppressor genes. Papillary carcinoma of

thyroid gland usually presents as a nodule that is firm, solitary, cold on isotope

scan, solid on thyroid ultra sound, and clearly different from the rest of the gland.

It is diagnosed by the presence of laminated calcified spheres called ‘’psammoma

bodies’. They grow very slow and remain cofined to the thyroid gland and local

lymph nodes for many years. Follicular carcinoma is somewhat more aggressive

than papillary carcinoma. These tumours often retain the ability concentrate

radioactive iodine; synthesize thyroglobulin and T3, T4. Medulalary carcinoma

is a disease of Ccells, with a prominent feature, calcification.

Thyroiditis:

i), Hashimoto’s thyroidits is an immunological disorder in which lymphocytes

become sensitized to thyroidal antigens and auto antibodies are formed that react

with antigens. Destruction of the thyroid gland results in a fall in serum T3 and T4

and a raise in TSH with thyroid gland enlargement.

ii) Subacute thyroiditis (also called de Quervain's thyroiditis) is thought to be

caused by a viral infection and often is associated with viral sore throat. The

viruses implicated are influenza, echo, adeno and Coxsackie virus. Some of

these patients eventually develop autoimmune thyroid disease. A characteristic

clinical feature is pain in the region of the thyroid gland with or without fever. The

Hypothyroidism 51

Goiter

gland is firm and tender to palpation.

Histologically, the cells differ from Hashimoto's thyroiditis by their patchy

distribution. Affected follicles are infiltrated by mononuclear cells with partial or

complete loss of colloid. The follicular changes may progress to granuloma with

multinuclear giant cells. When the disease process subsides, an essentially normal

histological appearance is restored.

iii) Postpartum thyroiditis Postpartum thyroiditis is recognised as an

autoimmune thyroid disease (AITD) presenting three to six months after giving

birth, with a transient phase of destruction followed by a period of primary

hypothyroidism and eventual return to a euthyroid state within a year.A painless

goitre on clinical examination and a positive result for thyroid microsomal

antibody in immunological screening are usually found.

iv) Silent or painless thyroiditis is that form of AITD where there is no pain over

the thyroid area. The underlying mechanism is autoimmune dysregulation with

extensive lymphocyte infiltration, presence of plasma cells and circulating

autoantibodies. The course is mostly benign and self-limited.

v) Reidel's thyroiditis (chronic sclerosing thyroiditis) is very rare. A very hard,

painless goitre is usual and this can be associated with fibrosis elsewhere

(retroperitoneal or mediastinal fibrosis).

vi) Infective: Acute pyogenic (suppurative) thyroiditis is fortunately rare. The

commonest infective organism is Staphylococcus aureus. Usually the infection is

from a septic focus outside the thyroid gland. Surgical drainage is indicated when

pus is present. It is characterised by excruciating tenderness over the thyroid area

associated with systemic symptoms. Other rare infective causes of thyroid disease

are tuberculosis, coccidiodomycosis and pneumocystis. Tuberculous or

Pneumocystis carinii infection could indicate an acquired immunodeficiency state

as the underlying disease

Hypothyroidism 52

Galaganda

GALAGANDA

There is no direct mention of thyroid gland in ayurveda. But a

disease by the name galaganda is mentioned in samhitas. The earliest description

of neck swelling is found in atharva veda by the name apachi. Charaka first

described abt the disease galaganda. He mentioned this in sutra sthana 20th chapter

(maharogadhayaya) under the 20 varieties of sleshma vikaras.

Susutha has described that out of seven layers of the skin, the sixth

layer known as ‘’Rohini’’ is responsible for the development of galaganda.

“Shasti rohini nama vreehi pramanaa grandhyapachyamarbuda sleepda

galagandadhisthna”’ (Su. Sa. 4/4)

It is presumed that

1. The location indicated beneath the skin.

2. The sixth layer of the skin is the seat of various disorders including

Galaganda.

A definite anatomical description of thyroid gland could be seen

Susrutha samhita where he has described

‘’Nibadddah swayadhuryasya mushkavallambhate gale

mahan yadiva hraswo galagandam tamadiset’’ (Su. Sam. N.11)

Two encapsulated small or big swellings in the anterior angle of the

neck which hang like scrotum, is called as ‘’Galaganda’’. This view with similar

descriptions was also supported by another ancient Indian author i.e bhoja and

madhukosa.

Hypothyroidism 53

Galaganda

On the other hand, Charaka and Harita have mentioned that there is a

solitary swelling in the neck.

“Galasya parswe ganda ekah” (Cha. Chi.11)

Coming to the etiological factors may be broadly divided into

intrinsic and extrinsic factor.

The intrinsic factors are 1. Dosha- Vata and Kapha

2. Dushya- Meda

The extrinsic factors include climatic conditions, water supply,

dietary conditions and other surroundings etc.

As regards geographical distribution of the disease and its role in the

aetiology Bhela samhitakara has described that sleepda and galaganda are more

common in prachya (eastern part) of the country.

“Sleepada galagandam cha prachysteshu drishyate”

Kashyapa samhitakara added that any part of the country which is

cold, damp, with densely grown long trees, water stagnation and heavy rains may

be prone for the development of Galaganda.( Ka. Khi. 25)

Susrutha stated that rivers flowing towards east may give rise to

the occurrence of goiter. Although this concept was given many centuries ago, but

still it is an accepted fact that sub-Himalayan range is known as goitrous belt.

Apart from this Bhela Samhitakara has also emphasized on dietary

factor, where he described that persons consuming predominantly fish on their

regular diet every day are liable to develop galgaganda.

Hypothyroidism 54

Galaganda

“Matsya anna bhojino nityam prachyaah syu kapha bittinah

sleepdam galagandam cha prachya sastheshu drishyate.” ( Bhe. Sam)

Harita samhitakara described the role of contaminated water, low

nutritional and bacterial infections in the precipitation of Galaganda

“Dustambu panaka…………krimijadosha ganasha gandat”(Ha. Sam)

Samprapti:

Samprapti of goiter mentioned by different authors resembles almost

similar. As per charaka vitiated kapha gets accumulated in the exterior of the neck

and also due to involvement of mamsa dhatu and causes gradual onset of swelling

known as Galaganda.

Where as sushruta is of opinion that galaganda is produced, when

vitiated vata & kapha dosa induces metabolic disbalance of meda and majja dhatu

in the neck region.

Types: Vataja, Kaphaja and Medaj are the three verities of Galaganda.

Treatment

The treatment of Galaganda includes sodhana and samana

therapies like Vamana, Nasya, Rakta Mokshana,Chedana, Bahya lepas, and

Teekshna ushna aushadhi’s.

Asadhya lakshana’s:

A case of galaganda attended with difficult respiration, a softening

of the whole body, weakness, a non relish for, loss of voice as well as the one

which is more than of a year’s standing should be abandoned by the physicians to

be incurable.

Hypothyroidism 55

Galaganda

Galaganda can be correlated with goiter and some tumour

pathology, where thyroid functions may or may not be affected.

But hypothyroidism is not a mere localized disease. It has many

symptoms related to many systems of the body. So it is better not to restrict

hypothyroidism to the disease mentioned as Galaganda.

Hypothyroidism 56

Hypothyroidism in ayurveda

HYPOTHYROIDISM IN AYURVEDA

Lot of attempts has made to put an ayurvedic frame to the

disease hypothyroidism. There are quite a few concepts which may probably

resemble few symptoms of the disease.

Some of them are

1. Agnimandya, including Jatharagni, Bhutagni and Dhatwagni.

2. Kaphaja sodha, “peedite no nnamati” with myxedema.

3. Astaunindita purusha, atihraswa with cretinism.

Agnimandhya:

The major function of thyroid gland is to control the rate of

metabolism. The principle function of it is to act as a catalyst –of the nature of a

‘’spark’’ for the maintenance of oxidative metabolism in most tissues. Cells in the

body take their "cue" from thyroxine. The amount of stimulation the cells receive

from thyroxine will determine how "quickly" they perform their functions.

Agni is derived from the word “angati vyapnoti iti agnihi” means

which is capable of penetrating into minute spaces. So some believe that thyroxine

has a close resemblance with agni.

All the ayurvedic physicians are very much aware about the

importance of Agni.

Vagbhata enumerated agni25 as

• Jatharagni

• Bhutagni

• Dhatwagni

Hypothyroidism 57

Hypothyroidism in ayurveda

If these Agni’s fail to perform their optimum function, their sub

normality leads to agnimandhya at different levels. The following points will

support the concept of agnimandhya i.e Jatharagni, Bhutagni, Dhatwagni mandhya

in hypothyroidism.

Table showing the normal and abnormal functions of the agni related to

hypothyroidism.

Agni Normal function Features of Mandagni /hypothyroidism

Jatharagni Digestion and assimilation of food constituents.

Diminished power of digestion, assimilation, constipation, poor appetite,

Rasagni Supply of absorbed nutritive material to all body tissues for growth and repair.

Easy fatigability, dry skin, irritability, lack of sweating As artava is the upadhatu, menstrual irregularities come under this.

Raktagni Responsible for tissue nutrition, adequate haemopoeisis, which in turn gives luster to the body.

Anemia, Skin infections like vitiligo, alopecia, Edema, brittle dull hair, brittle nails, cold intolerance etc.

Mamsagni Maintenance of adequate muscle mass, physical strength.& greasyness to the skin.

Physical strength lowered. Muscle cramps, stiffness etc noted

Medogni With adequate fat and sweating gives unctuous skin &physical strength

Hyperlipidemia, obesity, goiter,

Asthyagni Creation of healthy bones, joints, body hair, nails etc. physical and mental activeness

Loss of body hair, pains in the bones and joints and easy fatigability

Majjagni Adequate unctuousness of body, maintaining fertility

Lowered physical strength, vertigo

Sukragni Maintaining fertility and libido of the individual

Decreased libido, infertility etc

Hypothyroidism 58

Hypothyroidism in ayurveda

In Susruta Samhita Sareera Stahna 3rd chapter he described about the

hump-backed, crooked armed, lame dwarf child occurring due to the desires of the

douhrada not being gratified30. This can be correlated with congenital

hypothyroidism. Similar description is found Astanindita Purusha description, in

which Atihraswa purusha may be correlated with cretin child.

Kaphaja sodha27: some consider kaphaja sodha as myxedema. The only

symptoms correlates here was “peedite nonnamati”, non pitting edema.

Hypothyroidism 59

Sadhyasadhya

SADHYASADHYA

As a general rule, the disease without any Upadravas, or Arishta

Lakkshanas which is nearly manifested and in which more than one dosha is

involved is sukhasadhya. The term Asadhya denotes the bad prognosis of a

particular disease. Asadhya is two types. Those are Yapya and Pratyakhyeya.

Yapya means that the treatment should continue jeevana paryantam and

pratyakhyeya indicates achikitsavastha of vyadhi27. The following are the Asadhya

Lakshanas.

Hypothyroidism is classified into primary and central

hypothyroidism. Central hypothyroidism results when there is any defect in the

hypothalamus or pituitary level. This form is very rare and may not be amicable to

ayurvedic treatment. The extra thyroidal causes like thyroid hormone resistance is

also not curable.

The causes of primary hypothyroidism may be classified into the

following types11.

1. Genetical and Hereditary.

2. Congenital.

3. Autoimmune thyroid deceases

4. Iodine deficiency.

5. Side effects of surgery and allopathic medicines.

l. Genetical and hereditary defects that cause hypothyrodism come under

Adibala Pravritta Vyadhi and no treatment is suggested in the text.

2. Congenital defects comes under Janma Bala Pravritta Vyadhi and it may

be due to two causes

Hypothyroidism 60

Sadhyasadhya

i) Rasakritah this is due to under nourishment during intra uterine like.

ii) Dauhridapacharakritah: Unfulment of desires during pregnency causes

certain defects to the foutes.

These deceases are preventable if followed pathyapathya during

pregnenancy as prescribed in ayurvedic texts.

3. Autoimmune thyroid diseases: autoimmune thyroid disease is

characterized by gradual lymphatic infiltration and progressive destruction of the

functional thyroid tissue. So it may be Yapya, means that the treatment should be

continued Jeevanaparvantam.

4. Iodine deficiency: is easily treatable by supplementing iodine, it comes

under Sukha Sadhya.

5. Side effects of surgery and allopathic medicines: If hypothyroidism

results due to surgery, radiation and allopathic drugs, there will be some loss of

functional thyroid tissue. So it may be Kasta Sadhya.

6. If hypothyrodism results due to functional defects in thyroid hormone

biosysnthesis and release it is sadhya.

7. The patient who has complications like heart diseases like bradycardia

and cardiomagaly, myxedema coma, are Pratyakhyeya indicates Achikitsavastha

of Vyadhi.

Hypothyroidism 61

Chikitsa yojana

CHIKITSA YOJANA24

‘’Vikaranamakusalo na jihriyat kadachana

Nahi sarva vikaranam namoto asti dhrivasthitih’’

--Cha. Chi. 18/44

Ayurveda doesn’t emphasize on the exact nomenclature of the

disesase rather than it insists on diagnosis of the constitutional status of the disease

as mentioned in charaka.

On the basis of Ayurvedic principles the following are the main

causes for hypothyroidism.

1. Genetical and hereditary defects comes under adibala pravritta vyadhis,

so no treatment suggested.

2. Congenital defects come under janmabala pravritta vyadhis. Thyroid

gland Agenesis, Dysgenesis, Ectopic thyroid gland comes under this

category.

3. Iodine deficiency is the main common cause for hypothyroidism. So

‘’Sarvadha sarva bhavanam samanyam vriddhikaranam25’’ applies here.

4. Auto immunity is another common cause so Immuno modulatory drugs

are recommended here.

5. Side effects of surgery and radiation: kasta sadhya.

6. For transient hypothyroidism no specific treatment is required.

Hypothyroidism 62

Chikitsa yojana

7. If there is functional loss of thyroid tissue or functional defects thyroid

stimulatory drugs are beneficial.

8. Selection of drugs acting at various levels:

1. At hypothalamo pituitary level: anti stress drugs, medhya rasayana

drugs, nasya karma may be beneficial.

2. At thyroid gland level: thyroid stimulatory drugs are recommended

here.

3. At metabolism level: deepana, pacahana, ushna, teekshna, sukshma,

,lekhana drugs which pep-up body metabolism is recommended.

4. Immuno modulatory drugs for autoimmune related hypothyroidism.

“Samprapti vighatana” is one of the main principles of treatment.

Whatever may be the etiology of the disease, it results in under active condition of

the thyroid gland and ultimately slowing down of the body’s metabolism. So the

treatment should aim to stimulate the thyroid gland. Thyroid stimulatory drugs

like guggul should be selected to treat the disease.

As the symptoms of hypothyroidsm are notorious, the symptomatic

treatment is followed according to the suitabily of the individual cases, i.e.,

sthoulya, sodha etc.

Selenium is required for a number of enzymes known as

selenoproteins. The chemical reaction, which converts thyroid hormone T4 into

T3, is catalyzed by specific selenoproteins. Selenium deficiency can impair

thyroid function.

In recent studies Selenium supplementation reduced thyroid

antibodies (TPOAb) by 40% in three months in a blinded controlled prospective

Hypothyroidism 63

Chikitsa yojana

study in female patients with autoimmune thyroiditis. Selenium is also a cofactor

for type I hepatic 5'-deiodinase, the enzyme that converts T4 to the more active

T3, and degrades rT3. The drug Pippali, increases the absorption of Selenium it is

very helpful in this condition; this may be cause for the effectiveness of

vardhamana pipppli in hypothyroid conditions.

Shilajit is believed to be useful in hormonal imbalance conditions,

nasya with anutaila, pushpadhanwaras, arogya vardhinivati,

punarnravamandura, chandraprabhavati, navakaguggulu,kumbha jatuvati,

loha rasayana are found in usage, but requires scientific studies to know its

efficacy, dosage, complications, duration etc.

Zinc is required for the action of Thyroid Stimulating Hormone. The

zinc/copper balance also has a big influence on the progesterone/estrogen balance

in women, which has a significant influence on thyroid function.so the drugs

which contain zinc may be useful.

Iron is essential for the conversion of phenylalanine, an essential

amino acid, to tyrosine. So the iron containing medications may be useful.

Heavy metals such as cadmium, lead & mercury can inhibit thyroid

function. So care must be taken when prescribing lead and mercury preperations to

the hypothyroid patients.

Further research is required to proove the efficacy of these drugs.

Hypothyroidism 64

Pathyapathya

PATHYAPATHYA24

AHARA:

The diet should be high in fibre and low in calorie. It should also

contain adequate proteins, fat, minerals and vitamins. But high protein diet will

worsen constipation if that is one of the symptoms. The fat allowance should not

exceed more than 30 gm per day. Salt intake should be kept at a minimum and

limited to 1-2 tsp per day. Avoid salted confectioneries, chips and pickles.

Eating goitrogenic foods such as rapeseed, cabbage, Brussels sprouts,

broccoli, cauliflower, sweet potatoes, maize, lima beans, soya and pearl millet

should be limited. These foods contain natural goitrogens, which are chemicals

that cause the enlargement of the thyroid gland by interfering with thyroid

hormone synthesis. Cooking is known to make the goitrogens elements less

effective but it would be wise not eat these foods raw.

Fats, sugars, sodium chloride, red meat and egg intake should also be

restricted. Avoid caffeine drinks like coffee, cola. Caffeine and other stimulants

interfere with T3 and adrenal hormone metabolism while in the body.

Smoking depresses TH levels and produces a chronic underlying

hypothyroidism. Research shows that nicotine increases the synthesis of T3 from

T4 in the brain, while alcohol and opiates block the breakdown of T3 in the brain.

Paradoxically, some substances labelled depressants such as alcohol

or opiates can increase T3 levels by impairing the breakdown of T3 in the brain,

thus lifting mood. This may be one reason why these substances are so addictive.

Foods that contain iodine such as kelp, beetroot, radish, parsley,

potatoes, fish, oatmeal and bananas should be kept in the diet.

Hypothyroidism 65

Pathyapathya

Certain foods, supplements and medications can impair absorption of

synthetic thyroid hormone. These include: 1. Iron supplements or vitamin

supplements containing iron; 2.Calcium supplements; 3.Soybean flour; 4.

Aluminum hydroxide, a popular antacid; 5. Sucralfate, an ulcer medication;

6.Some cholesterol-lowering drugs, such as cholestyramine and colestipol

VIHARA:

Another important factor in the treatment of hypothyroidism is

exercise. Exercise increases tissue sensitivity to the thyroid hormone and

stimulates thyroid gland secretion. An exercise regime of between 15-20 minutes

per day will be beneficial with hypothyroidism. This exercise needs to be

strenuous enough to raise the heartbeat, an exercise such as walking, swimming,

running and cycling.

But in patients who have hypothyroidism have generalized

hypotonia and may be at risk for ligamental injury, particularly from excessive

force across joints. Thus, patients should exercise caution with certain activities,

such as contact sports or heavy physical labor. Patients with uncontrolled

hypothyroidism may have difficulty maintaining concentration in low-stimulus

activities and may have slowed reaction times. Patients should use caution if an

activity has a risk of injury (e.g.operating presses or heavy equipment, driving).

Physical and emotional stress inhibits the thyroid gland secretion due

to reduction of thyrotrophin output. So reduction of the stress is very essential for

proper functioning of the gland.

YOGA:

Sarvangasana is the most suitable and effective asana for the thyroid

gland. An enormous pressure is placed on the gland by this powerful posture. As

thyroid gland has one of the largest blood supplies of the any organ, the pressure

Hypothyroidism 66

Pathyapathya

has dramatic change on its function, improving circulation and squeezing out

stagnant secretions. After sarvangasana practice of matsyasana and halasna is

beneficial. Other effective asanas include surya namaskara, pavanamuktasana with

emphasis on head and neck exercises, yoga mudra, sputa vajrasana and all

backward bending asanas.

PRANAYAMA:

The most effective pranayama is ujjayi. It acts on the throat and its

relaxing and stimulating effects are most probably due to stimulation of ancient

reflex pathways within the throat area, which are controlled by brain stem and

hypothalamus. Nadi sodhana pranayama is useful in re-balancing metabolism.

Hypothyroidism 67

Criteria for the drug selection

CRITERIA FOR THE SELECTION OF THE DRUG

KNG AND SHIGRU PATRA KWADHA

The present trial drug Kanchanara Guggulu24 (Sa. Sam.), is

found in usage for many years for Gandhamala, Apachi, Arbuda, Grandhi, Kushta,

etc, has been selected to evaluate the efficacy of this drug in hypothyroidism.

The main ingredient Guggulu has thyroid stimulating property

along with tridosha hara, rasayana, antiinflammatory, hypo-cholesterogenic, hypo-

lipodemic, reduces total serum cholesterol and serum lipid-phosphorus, appetizer,

antisuppurative, aphrodisiac; these are all very beneficial in hypothyroid

conditions.

This research work was done by Dr. Tripathi and others. Animal

studies have revealed that Guggulu supports healthy thyroid function, mostly by

increasing the conversion of less active Thyroxin (T4) to more active

Triiodotyronine (T3) through increasing thyroid proteolytic activity and the uptake

of iodine into thyroxin, and without increasing the production of Thyroid

Stimulating Hormone.33

KANCHNARA26,28: The synonym of Kanchanara as “gandari” itself indicates its

property as anti goiter drug. The action of kanchanara in cases of goiter is most

probably by its prabhava not merely by rasa, guna, veerya or vipaka. It has

Prabhava (specific action) – Gandmalanashak. It is a specific herb for swollen

lymph nodes, cervical adenitis, scrophularia or swollen glands in general. It

effectively flushes the lymphatic system of toxins, sluggishness and accumulated

wastes. Also may be beneficial where the sinuses are congested because of the

sluggish lymphatic system. It is a powerful decongestant.

Hypothyroidism 68

Criteria for the drug selection

The other ingredients triphala, trikatu, trijataka are also may be

useful in hypothyroid condition as these are deepana and pachana drugs they may

be helpful to pep up body’s sluggish metabolism and also may enhance the action

of the drug Guggulu.

SHIGRU PATRA28:

Iodine is an essential component of thyroid hormones, T3 and T4.

Iodine is essential for the formation of thyroid hormones. Iodine deficiency is one

of the main causes of hypothyroidism. So according to sarvadha sarvabhavanam

samanyam vriddikaranam iodine deficiency is supplemented by administering the

drug which contains iodine. Shigru leaves rich in iodine, appears to provide it

with the nutrition and substrates the thyroid gland requires. It contains essential

aminoacids, vitamins, having deepana properties, vatakapha hara, sodhahara,

chakshushya properties and is indicated in gandamala, medo roga, apache,

vidradhi etc.

Hypothyroidism 69

KANCHANARA GUGGULU

SHIGRU PATRA KWATHA CHURNA

KANCHANARA

GUGGULU

SHIGRU

Kanchanara guggulu

DRUG REVIEW

KANCHANARA GUGGULU 24

Kanchanara guggulu a well-known drug in Ayurveda is found in

usage from many years for apache, arbuda, gandhamala etc.

“Kanchanara twacho grahyam palanam dasakam budhaih

Triphala shatphala kaarya trikatusyatphalatrayam

Palaikam varunam kuryadela twakpatrakam tadha

Ekaikam karsha matram syat sarvanyekatra churnayet

Yavadchurnamidam sarvam tavanmatrastu gugguluh

Sankutya sarvamekatra pindam kritwa cha dharayet

Gutika ssanikah karyah pratargrahyayadochitah

Gandamaala jayantyugram mapachimarbudanicha

Grandhin vranamscha gulmanscha kustanicha bhagandaram”

(Sa. Sam)

10 palas of bark of Kanchanara, 6palas of Triphala, 3palas of

Trikatu, 1 pala of bark of Varuna, karsha each of Ela, Twak, Patra, Guggulu

equal to the quantity of above are rolled into pills of sana.

It is indicated in Gandamala, Apachi, Arbuda, Granthi, Vrana, Gulma,

Kusta, Bhagandara etc.

Dosage: 2-3 tab b.d

Hypothyroidism 70

Kanchanara guggulu

INGREDIENTS OF KANCHANARA GUGGULU

1. GUGGULU 26,27,28:

Synonyms: Kousika, Devadhupa, Palamkasha, Pura

Botanical name: Commiphera mukul

Family: Burseraceae

Vernacular names:

Hindi: Guggula

Telugu: Guggilam

Kannada: Kanthagana

Gana: Sanjna sthapana (Charaka), Eladi ( Susrutha & Vagbhata)

Gunas:

Rasa: Tikta, katu

Guna: Laghu, Ruksha, Visada, Sukshma, Sara(old), Snigdha and

Picchala (new)

Virya: Usna

Vipaka: Katu

Karma: Tridosha hara, Deepana, Brimhana, Vrsya(nava), Lekhana (purana),

Rasayana.

Indications: Medo roga, Prameha, Kusta, Ashmari, Amavata, Sopha, Grandhi,

Apachi, Gandamala, Arshas, kusta etc.

Useful part: Niryasa

Research work28,33,35:

The primary chemical constituents of Guggula include phytosterols, gugulipids, and

guggulsterones.

• Animal studies have revealed that guggul supports healthy thyroid function,

mostly by increasing the conversion of less active Thyroxin (T4) to more

active Triiodotyronine (T3) through increasing thyroid proteolytic activity and

Hypothyroidism 71

Kanchanara guggulu

the uptake of iodine into thyroxin, and without increasing the production of

Thyroid Stimulating Hormone33.

• Z guggulsterone also increased the thyroid activity as evidenced by increased

the thyroid activity and increased iodine uptake and increase in proteolytic and

peroxidase activity.

• Guggul helps reduce high cholesterol, because it lowers harmful low-density

lipoproteins while elevating the beneficial high-density lipoproteins. It appears

to work through several mechanisms, including inhibition of HMG-CoA

reductase (the enzyme which controls the body’s synthesis of cholesterol),

increasing the release of excess lipids through the feaces, an action similar to

the drug Cholesrymine, and its support of thyroid hormone production.

• It prevented the deposition of fat in the adipose tissue, probably due to

increased lipolysis.

• In order to find out the effect of Guggulu on endogenous hyperlipimia, its

effect on neomercazole and estrogen induced hypercholesterolemia and

hyperlipidemia was also studied. This reveals an important fact that it

successfully neuturalized the action of neomercazole on thyroid. This gave a

lead that hypocholesterolemic and hypolipidemic action of this drug is

medicated through the thyroid gland.

• It helps prevent blood platelet aggregation and breaks up already formed blood

clots and keeps potentially deadly blood clots in check by increasing

fibrinolysis. Thus, it helps prevent heart disease and stroke.

• Its effect on aortic atherosclerosis and coronary thrombosis was also extended

and it was observed that Guggulu retarded the process of atherosclerosis to a

great extent and prevented the process of thrombosis.

• Guggul lipid stimulates the activity of white blood cells in the body,

contributing to the build-up of the immune system.

• Guggul lipid also helps eliminate and expel dead tissues, wastes, and toxins

from the body.

Hypothyroidism 72

Kanchanara guggulu

• Guggul lipid has been known to relieve coughing and lung congestion, soothe

mucous membranes and alleviate other respiratory problems.

• Guggul lipid may also be used to treat arthritis and reduce inflammation of the

joints.

• A small controlled trial compared oral guggulipid against tetracycline for the

treatment of acne, and reported equivalent results.

• There were also significant reductions in skin fold body fat measurements at

the triceps, calf, and shoulder; biceps skinfold fat was also considerably

reduced in the mildly overweight

• Several animal studies have supported an anti-inflammatory effect for Guggul

– a traditional use for this herb.

• Guggul has also traditionally been used for support in a variety of skin

disorders. One small trial found Guggul to be as good as tetracycline for

people suffering with scarring, cystic acne, an effect most strongly noted in

those with very oily skin.

Cautions:

• Guggul is traditionally believed to stimulate the menstrual cycle and the tone

of the uterus; it is therefore best avoided in cases of pelvic inflammatory

disease or menorrhagia.

• Guggul should not be used in cases of hyperthyroidism.

• May potentiate or alter the effects of thyroid medications.

• Mild GI problems have been noted in a few people.

• A small subset of Guggul users may develop a rash, which disappears when

they stop taking the supplement.

• Guggul reduces the bioavailability of blood pressure drugs diltiazem

(Cardizem®) and propranolol (Inderal®), as well as the cancer drug

cyclophosphamide. Guggul must not be taken with acetaminophen (eg.

Tylenol)

Hypothyroidism 73

Kanchanara guggulu

KANCHANARA 27,2830

Synonyms: Gandari, Sonapushpaka, Kancanaka, Kovidara, Swalpakesari,

Yugmapatraka, Camarika.

Botanical name: Bauhinia variegata

Family: Caesalpinaceae

Vernacular names:

Telugu: Devakanchanamu

Hindi: Kachnar

Ganas: Vamanopaga (charaka) Kashaya varga ( susrutha )

Gunas:

Rasa: Kasaya Veerya: Seta

Guna: Ruksha, Laghu Vipaka: Katu

Karma: Kapha-pittahara, Grahi, Deepana

Indications: Gandamala, Rakta pradara, Rakta pitta, Mutra kricchra, Vrana, Arsa,

Masurika.

The synonym of kanchanara as gandari itself indicates its property as antigoiter

drug.

It is a specific drug for swollen lymph glands or swollen glands in general.

Traditionally it is used to treat thyroid diseases and glandular enlargements.

VARUNA 27,28,30

Synonyms: Varana, Kumaraka, Tikta saka, Setu, Saka druma, Tamalaka, Sweta

pushpa

Botanical name: Crataeva religiosa

Family: Capparidaceae

Vernacular names:

Hindi: varuna

Telugu: ulimiri chettu

Hypothyroidism 74

Kanchanara guggulu

Ganas : Tikta skanda (charaka), varunadi, vata samsamana, kapha

samsamana(susrutha), varunadi ( vagbhata).

Gunas:

Rasa: tikta, kashaya Veeerya: ushna

Guna: laghu, ruksa Vipaka: katu

Karma: Kapha vata hara, Deepana, Krimighna

Indications: Asmari, Mutrakricchra, Vidradhi, Gulma, Gandamala.

It contains lupeol, a chemical that deactivates enzymes that needed to manufacture

inflammation inducing leukotraines and also reduces the levels of various

laboratory markers of kidney damage.

Scientific research has confirmed that varuna deactivates the enzyme glycolate

oxidase. This reduces the body's production of oxalates, which combine with

calcium to form kidney stones.

TRIPHALA30

“Pathya vibhita dhtrinam phalsyat tripala samai”

Bha. Pra. Purva-5/45/46

Haritaki, vibhitaki, amalaki these are three drugs in equal quantity is called as

triphala or phalatrika or vara.

Karma: kaphapitta hara, deepaneeya, chakshushya, vishama jwara, prameha,

kustaharam.

It is an excellent laxative which takes away fats from the body and

reduces weight. It is said to promote normal appetite, good digestion. It has strong

purifying and antioxidant qualities.

TRIKATU30

“Vishwopkulya maricham trayam trikatu kadyate” Bha. Pra. Purva-5/70

Trikatu contains three ingredients i.e vishwa (shunti), upakulya (pippali),Mareecha

Gunas: katu – rasa, ushna- veerya, madhuara – vipaka.

Karmas: Deepana, Gulma, Medoroga, Prameha, Sleepada, Peenasa, Swasa, Kasa

hara.

Hypothyroidism 75

Kanchanara guggulu

TRIJATAKA30

“Twagela patrakai stulyai strisugandi trijatakam”

Bha. Pra.Purva.5/87

Twak, Ela, Patri in equal parts is called as trijataka.

Gunas: rooksha, teekshna, ushna,

Karma: Mukha durgandha nasaka, Laghu, Pitta-agni krit, varnyam, kapha vata

vishapaham.

Hypothyroidism 76

Shigru

SHIGRU 27,28

Synonyms:

Shobanjana: “Susthu bhanakti mukham sobhanjanah”

Shigru: “Shinoti taikshnyat sigruh”

Tikshna gandha: “Tteekshnam gandho asyah teekshna gandhah”

Mochaka: “Munchati rogaan iti mochakah”

Aksheeva: “Ksheebyantyanena vrishytwad aksheeva”

Bahupatra: “Bahu patraat”

Botanical name: Moringa oleifera

Family: Moringaceae.

Vernacular names-

Hindi: Sahijana

English: Drumstick tree

Telugu: Munaga

Ganas: Krimighna, swedopaga, sirovirechanopaga, katuka skanda (charaka),

varunadi and sirevirechana gana’s (susrutha) varunadi gana (vagbhata).

Guna’s

Rasa: Katu, tikta Guna: Laghu, rooksha, teekshna

Veerya: Ushna Vipaka: Katu

Karma: Kapha vata hara, sukrala, grahi, dipana, hridya, krimighna, chakshushya

Indications: Kapha vata hara, pliha roga, galaganda, sirahsoola, kandu, sotha,

apachi, vrana, medoroga, vidradhi, gulma etc.

Useful parts: Root, bark, stem, leaves, flowers, seeds.

Root:

Root bark contains 2 alkaloids moringine and moringinine. First one was

competitively inert, but moringine acts n sympathetic nerve endings as well as

cardiac and smooth muscles all over the body. It produces raise of blood pressure

stimulation of heart and contraction of blood vessels. It relaxes bronchioles,

inhibits tone and movement of the intestines and contracts the uterus in guinea pig

Hypothyroidism 77

Shigru

and rabbits. Root bark contains an antibiotic pterigospermin, which is active at

ph5 and less active at ph 8. It is stable in the presence of blood and gastric juice

but breaks down in the presence of pancreatic juice. It is active against

Solmonella, E.coli, Shigella, Micro coccus, and Mycobacterium etc and also

active against Fungi. 50%Ethanolic extract of root bark showed anti viral activity.

It contains an alkaloid named Spirochin, its pharmacological and chemical trails

showed action directly on myocardium. It also contains traces of essential oil,

phytosterol, waxes and resins.

Stem: Stem bark contains sterols and terpens, which show anti fungal activity

against candida albicans, etc. Gum exudates contains Arabinose,

Galactose,Glucaronic acid, Rhamnose, Mannose and Xylose in molar ratio of

14.5, 11.3, 3.2, 1, 1 ratio.

Leaves:

Leaves contain per 100 g 8.Protein: 6.7 g

1. H2O-7.5 g 9.Fat: 1.7 g

2. Total carbohydrate-14.3 g 10.Fiber: 0.9 g

3. Ca-440 mg 11.P- 70mg

4. Fe-7 mg 12. Cu- 110mg

5. Iodine- 5.1 mg 13.Vit A-11,300 IU

6. Vit B-120 mg 14.Nicotinic acid-0.8 mg

7. Ascorbic acid- 220 mg 15. Tocopherol- 7.4 mg

Leaf amino acids:

1. Arginine -6.0 g 7.N-16 g

2. Histidine- 2.1g 8. Lysine- 4.3 g

3. Phenylalanine-6.4 g 9. Tryptophane- 1.9 g

4. Methionine-2.0 g 10.Lucine-9.3 g

5. Threonine- 4.9 g 11.Isoleucine-6.3 g

6. Valine-7.1 g

Hypothyroidism 78

Shigru

Research works:

• It contains 4-[(4'-O-acetyl-alpha-L-rhamnosyloxy) benzyl] iso thiocyanate and

the thiocarbamate glycosides niaziminin A and B isolated from ethanolic

extract of Moringa oleifera, showed hypotensive activity

• The fresh leaf juice and aqueous extracts from the seeds inhibited the growth

of Pseudomonas aeruginosa and Staphylococcus aureus when tested by a disk

diffusion method.

• Estrogenic substances, including the anti-tumor compound, b-sitosterol, and a

pectinesterase are also reported

• In a study conducted it was found that administration of the crude leaf extract

of Moringa oleifera along with high-fat diet decreased the high-fat diet-

induced increases in serum cholesterol level to a statistically significant extent

• Niazimicin an alkaloid isolated from seeds of Moringa oleifera when

subjected to in vivo test was found to have potent antitumor promoting activity

in the two-stage carcinogenesis in mouse skin using 7,12-dimethylbenz

(a)anthracene (DMBA) as initiator and TPA as tumor promoter.

• Three thiocarbamate (TC) - and isothiocyanate (ITC)-related compounds,

isolated from the leaves of Moringa oleifera, are observed to be inhibitors of

tumor promoter teleocidin B-4-induced Epstein-Barr virus (EBV) activation in

Raji cells in a study conducted.

• The methanol fraction of Moringa oleifera leaf extract was found to possess

significant protective actions in acetylsalicylic acid; serotonin and

indomethacin induced gastric lesions in experimental rats.

• In another study, a significant enhancement of the healing process in acetic

acid-induced chronic gastric lesions was observed with the extract-treated

animals.

• It contains 4times Calcium than Milk, 4times Vit A than Carrots, 3times vit C

than oranges, 2times Vit K than banana and 2times protein than milk.

Hypothyroidism 79

Shigru

Pod: Per 100 g, the pod is reported to contain

1. H2O- 86.9 g 8.Protein- 2.5 g

2. Fat-0.1 g 9.Total carbohydrate- 8.5 g

3. Fiber -4.8 g 10.Ash-2.0 g

4. Ca-30 mg 11.P-110 mg

5. Fe-5.3 mg 12.Niacin- 0.2 mg

6. Vit.A-184 IU 13.Ascorbic acid-120 mg

7. Cu-310 mg 14.Iodine-1.8 mg

Pod amino acids:

Arginine: 3.6 g N:16 g

Histidine: 1.1 g Lysine: 1.5 g

Tryptophane:0.8 g Phenylalanine:4.3 g

Methionine:1.4 g Threonine: 3.9 g

Leucine: 6.5 g Isoleucine:4.4 g

Valine :5.4 g

Seeds:

Seed oil composed essentially of Oleine, Margarine and Stearine. It is useful

externally for relieving pains. Biological activity studies have confirmed the anti

inflammatory, antispasmodic and diuretic action of the seeds.

Seed kernel (70–74% of seed) contains 4.08 H2O, 38.4 g crude protein, 34.7%

fatty oil, 16.4 g N free extract, 3.5 g fiber, and 3.2 g ash.

Flowers:

Flowers contain Quercetin and Kaempferol. It acts as a tonic and increases the

flow of Bile.

Hypothyroidism 80

Material and methods

MATERIALS AND METHODS MATERIALS:

1. PATIENTS:

To evaluate the efficacy of the drug Kanchanara Guggulu and

Shigru Patra Kwatha in the management of Hypothyroidism, 32 patients of

hypothyroidism were selected from the O.P Dept of Dr. B.R.K.R.Govt Ayurvedic

Hospital, Hyderabad.

32 patients were included and examined thoroughly examined

and the Diagnosis of hypothyroidism is based on a person's medical history, a

physical examination, and blood tests. Of the blood tests for hypothyroidism, the

TSH is the most sensitive test. The role of TSH is to stimulate the thyroid gland to

produce thyroid hormone when the level of hormone in the body drops. If the TSH

level is above 6, then a diagnosis of hypothyroidism was made.

The symptoms of hypothyroidism vary widely, from no

symptoms to marked symptoms. The symptoms of hypothyroidism are notorious

for their nonspecific nature and for the way in which they mimic many symptoms

of other diseases. As Hypothyroidism doesn’t have any characteristic symptoms,

the following most common symptoms were carefully screened.

Inclusion criteria:

1. Weight gain/unable to loss weight

2. Vertigo

3. Easy fatigability

4. Lethargy

5. Cold intolerance

6. Hair loss

Hypothyroidism 81

Material and methods

7. Slowness of memory, intellect and thought

8. Anorexia

9. Constipation

10. Gaseous distention

11. Hoarseness/slowness of voice

12. Menstrual irregularities

13. Oligomenorrhoea /Amenorrhea

14. Parasthesias

15. Muscle cramps and weakness

16. Muscle stiffness and aching

17. Dry skin

18. Coarse, brittle, dull hair

19. Puffiness of the face, hands, feet

20. Slow reflexes

21. Goiter

Exclusion criteria:

1. Patients with Cardiomegaly and Bradycardia.

2. Patients who are above 65 yrs and using the allopathic drug thyronorm.

3. Patients who are suffering from hypothyroidism for more than 10 years.

2. DRUGS:

1. KANCHANARA GUGGULU ( Sa. Sam )

The drug Kanchanara guggulu a compound Ayurvedic

preparation consists of Guggulu, Kanchanara, Varuna, Triphala, Trikatu and

Trijataka (preparation of the drug mentioned in drug aspect). It is one of the

safest and the very useful drug in ayurveda, is found in usage for many years

for gandhamala, apachi, Arbuda, Granthi, Vrana, Gulma, Kusta, Bhagandara

etc. In the present study KNG is evaluated for thyroid stimulating activity.

Hypothyroidism 82

Material and methods

2. SHIGRU PATRA KWATHA:

Shigru is a well-known plant in India. It has deepana, pachana,

kapha vata hara properties. It is recommended in galaganda, kandu, sotha, apachi,

vrana, medoroga, vidradhi, gulma etc. As it is rich in iodine, which is the main

cause for hypothyroidism, is selected as anupana along with KNG.

Shigru leaves are dried and the powder was given to the patients

and advised them to make decoction.

Kwatha preparation: To the coarse powder of one part of drug, add 8 parts of

water, boil and reduce them to 1/4th and filter it.

THE METHODOLOGY:

The aim of the study of the study:

1. Normalize the levels of TSH in the fresh cases.

2. To maintain the TSH levels in the patients who are already

using the allopathic drug thyronorm and gradually replacing the

allopathic drug with the trail drug

Type of trial: Open trail

Mode of administration: Oral

Method of administration:

1. For fresh cases started immediately after the diagnosis

confirmed.

2. For the patients who are already using thyronorm advised

withdraw the 25 mcg of the drug before starting the rail

drug.

3. The patients were observed carefully for I month, if they are

comfortable with the drug and dosage and TSH levels are

maintained well they are advised to withdraw another

25mcg. This way the drug is totally replaced with the trail

drug.

Hypothyroidism 83

Material and methods

Dose of the drug: i) Kanchanara guggulu 250mg b.d.

ii) Shigru patra kwatha 250ml b.d

Period of study: 3 months

Patients were advised not to take Kapha and Medo vardhaka Ahara and Vihara’s

like diwaswapna, madhura guru dravya sevana etc.

CLINICAL ASSESSMENT:

The progress of the patient is observed and recorded after every

15 days. This procedure is followed for duration of 90 days. After the completion

of the duration the results are assessed basing on observations. The results are

assessed in terms of complete relief, marked, moderate and mild relief and no

relief.

1. Complete relief: TSH levels normalized and 100% symptoms relieved.

2. Marked relief: TSH levels normalized and symptomatic relief up to 75%.

3. Moderate relief: TSH levels normalized and symptomatic relief up to 50-

75%.

4. Mild relief: TSH levels normalized and symptomatic relief up to 25-50%.

5. No relief: no change in the TSH levels and no symptomatic relief.

Hypothyroidism 84

Observation and results

OBSERVATIONS AND RESULTS

32 patients were selected from OP and IP departments of Dr. BRKRGovt.

Ayurvedic hospital, Erragadda; for the study on the effect of Kanchanara Guggulu

and Shigru patra kwatha on hypothyroidism.

The patients included in the study were examined thoroughly and the

diagnosis of Hypothyroidism is based on the patient’s symptoms and blood test,

i.e. thyroid profile. If the TSH levels are above 6, they were selected for the study.

The patients were classified into various groups according to their age, sex,

socioeconomic status, occupation, prakriti, sara, previous medical history, family

history, BMI etc and tabulated as shown below.

Classification of groups:

1. ACCORDING TO AGE:

32 patients were classified according to the ages as shown in table 4.1.

Maximum number of cases was seen in 20-30 yr age group.

Table 5.1 showing the incidence of hypothyroidism a/c to ages:

Age group No. of patients Percentage

10-20 3 9.37%

20-30 14 43.75%

30-40 12 37.5%

40-50 2 6.25%

50-60 1 3.125%

Hypothyroidism 85

Observation and results

2. ACCORDING TO SEX:

Out of 32 cases 30 cases were females, and only 2 male cases were seen.

Table 5.2, showing the incidence of hypothyroidism a/c to sex.

Sex No .of patients Percentage

Male 2 6.25%

Female 30 93.75%

3. ACCORDING TO OCCUPATION:

As hypothyroidism is seen more in those who adopt sedentary life

style, the occupation of the patient and nature of work is observed carefully.

Among the 32 cases the occupations were as summarized in the table.

Table 5.3 showing the incidence of hypothyroidism a/c to occupation.

Occupation No. of patients percentage

Housewife 18 56.25%

Student 7 21.87%

Hard worker 1 3.12%

Sedentary work 6 18.75%

4. SOCIO ECONOMIC STATUS:

The patients were observed as per the socio economic status

based on their monthly income. If the income is between 10,000- 20, 000 they

were taken as ordinary middle class. Above 20,000 as upper middle class, from

5,000-10,000 they were considered as lower middle class. If their income is below

Hypothyroidism 86

Observation and results

1000 rupees per month they were considered as poor. In the present study the

incidence of hypothyroidism is seen more in upper middle class people.

Table 5.4 showing the incidence of hypothyroidism a/c to SES.

Socio economic status No. of patients Percentage

Upper middle class 16 50%

Middle class 10 31.25%

Lower middle class 5 15.65%

Poor 1 3.125%

5. ACCORDING TO DIET: According to their diet 30 patients were non-vegetarians and 2 patients

were vegetarians out of 32 patients.

Table 5.5 showing the incidence of hypothyroidism a/c to diet.

Diet No.of patients Percentage

Vegetarian 2 6.25%

Non vegetarian 30 93.75%

6. ACCORDING TO FAMILY HISTORY:

Thyroid disorders are hereditary disease and runs in families. So family

history of autoimmune disorders, thyroid disorders are very important in

hypothyroidism.

Hypothyroidism 87

Observation and results

Table 5.6 showing the incidence of hypothyroidism a/c to family history.

Family history No. of patients percentage

Parents DM 6 18.75%

Mother hypothyroid 3 9.37%

Siblings hypothyroid 5 15.62%

Daughter hypothyroid 2 6.25%

Not associated 14 43.75%

7. PREVIOUS DRUG/MEDICAL HISTORY: Previous Drug/Medical History is the main cause of the disease. So the

patients were observed carefully for their previous medical history.

Table 5.7 showing the incidence of hypothyroidism, a/c to previous drug/ medical

history.

Previous medical history

No. of patients Percentage

Depression/insomnia 3 9.37%

Hysterectomy 6 18.75%

Steroids 1 3.125%

RA 1 3.125%

Not associated 21 65.62%

Hypothyroidism 88

Observation and results

8. ACCORDING TO PRAKRITI: The patients were assessed according to their prakriti. Kapha

predominance is seen more in the selected 32 patients.

Table 5.8showing the incidence of hypothyroidism, a/c to Prakriti.

Prakriti No. of Patients Percentage

Vata predominant 1 3.125%

Pitta predominant 2 6.25%

Kapha predominant 9 28.12%

Vatapitta 3 9.37%

Vatakapha 4 12.75%

Kaphapitta 13 40.62

9. ACCORDING TO SARA

Twak,Mamsa and Medo Sara predominance is seen more in the selected

32cases.

Table 5.9 showing the incidence of Hypothyroidism, a/c to Sara

Sara No. of patients Percentage

Twak 11 34.37%

Mamsa 15 46.87%

Medo 6 18.75%

Hypothyroidism 89

Observation and results

10. ACCORDING TO BMI:

Maximum incidence was found in those patients whose BMI is more than 20.

Table 5.10 showing the incidence of Hypothyroidism, a/c to BMI.

BMI No. of patients percentage

Below 20 1 3.12%

20-25 12 37.5%

Above 25 19 59.37%

Hypothyroidism 90

Observation and results

RESULTS

32 patients were recruited in the study and the assessment was done

for every 15days.

Of the 32 patients 16 patients were fresh cases and 16 patients are

already using the modern medicine eltroxin.

The results of the patients who completed the treatment of 90days

were analyzed.

In the 16 fresh cases the TSH levels came to normal range after the

completion of the treatment. The 16 who are already using allopathic medicine

were gradually replaced with the trial drug and the TSH levels were in normal

range as summarized in table 4.11 and 4.12.

Table 5.11 showing the levels of TSH before and after treatment:

Before treatment After treatment S.no

O.P.NO. TSH (mU/L) TSH (mU/L)

1 16884 9.66 3.93 2 22490 >100 3.29 3 5869 99.21 0.32 4 7289 11.13 0.01 5 11960 25.99 6.67 6 12460 116.6 1.09 7 6430 6.68 2.08 8 5892 10.73 3.56 9 6478 12.97 3.22 10 12926 22.38 0.90 11 11872 10.38 0.04 12 13482 48.72 1.47 13 5340 10.67 1.21 14 1792 11.32 3.54 15 8762 10.12 2.29 16 7280 100 5.89

Hypothyroidism 91

Observation and results

For the patients who are already using thyronorm advised

withdraw the 25 mcg of the drug before starting the trail drug. The patients were

observed carefully for I month, if they are comfortable with the drug and dosage

and TSH levels are maintained well they are advised to withdraw another 25mcg

and the drug was totally replaced with

Trial drug.

Table 5.12 showing the levels of TSH before and after the treatment in chronic

cases.

Before treatment

After treatment S.no

O.P.No.

Duration

Dosage of thyronorm TSH (mU/L) TSH (mU/L)

1. 2970 5yrs 50mcg 5.66 4.56 2. 5290 8yrs 75mcg 0.90 1.25 3. 3472 8mon 25mcg 1.47 1.81 4. 8960 2yrs 50mcg 2.27 3.46 5. 5269 5mon 25mcg 3.22 3.67 6. 6840 2yrs 100mcg 2.07 1.90 7. 10964 4mon 25mcg 4.12 3.54 8. 4263 6yrs 25mcg 4.12 3.57 9. 3940 7mon 50mcg 3.8 5.07 10. 10164 1yr 75mcg 2.68 1.21 11. 4170 21/2yr 50mcg 3.44 5.12 12. 3680 1yr 25mcg 1.11 1.80 13. 2865 1mon 25mcg 6.84 4.79 14. 6430 2yrs 75mcg 5.54 3.68 15. 10890 3yrs 25mcg 1.77 2.34 16. 5128 8yrs 50mcg 4.74 3.21

Many of the symptoms of hypothyroidism are non-specific. The

most common symptoms observed in the 32 selected patients, before and after

treatment were summarized as shown in below table.

Hypothyroidism 92

Observation and results

The most commonly seen symptoms are weight gain or unable to

loss weight, menstrual irregularities, vague body pains, constipation, puffiness of

the face, hands and feet. The rare symptoms are recurrent attacks of infections,

respiratory symptoms etc.

Table 5.13 showing the symptomatic relief percentage:

S.no The most common symptoms observed in 32 pt’s

BT AT Relief %

1. Weight gain/unable to loss weight 21 14 33.33% 2 Vertigo 14 2 85.7% 3 Easy fatigability 20 4 80% 4 Lethargy 26 8 69.2% 5 Cold intolerance 13 6 53.84% 6 Hair loss 18 7 61.1% 7 Slowness of memory, intellect and thought 23 7 69.5% 8 Anorexia 12 4 66% 9 Constipation 23 1 95.6% 10 Gaseous distention 16 1 93.75% 11 Hoarseness/slowness of voice 15 5 66.66% 12 Menstrual irregularities 16 2 87.5% 13 Oligomenorrhoea /Amenorrhea 12 5 58.3% 14 Parasthesias 19 7 63.15% 15 Mucle cramps and weakness 16 10 37.5% 16 Muscle stiffness and aching 15 7 53.33% 17 Dry skin 23 10 56.52% 18 Coarse, brittle, dull hair 11 4 63.63% 19 Puffiness of the face, hands, feet 22 3 86.36% 20 Slow reflexes 9 6 33.33% 21 Goiter 11 6 45.45%

The over all relief percentage:

The TSH levels became normal in the fresh 16 cases, showed a

p value of 0.0174, statistically significant. In 2 patients after withdrawl of the drug

no recurrence is noted even after 6months. In the chronic cases that are already

using the allopathic drug Thyronorm, the drug was gradually replaced with the

trail drug. The TSH levels were maintained during the replacement time.

Hypothyroidism 93

Observation and results

Out of the 32 recruited cases 6 cases shown marked relief. These 6

cases were fresh cases. Moderate relief was observed in chronic cases and in those

thyronorm withdrawal cases. 4 cases with long duration showed mild relief.

Complete relief and no relief were not observed in the present study.

Table 5.14 showing the result of overall treatment:

Relief No. of patients Percentage

Complete relief 0 0%

Marked relief 6 18.75%

Moderate relief 22 68.75%

Mild relief 4 12.50%

No relief 0 0%

Hypothyroidism 94

GRAPH 5.1 SHOWING THE INCIDENCE OF HYPOTHYROIDISM A/C TO AGE.

Graph5.1 show ing the incidence of hypothyroidism a/c to age

0

10

20

30

40

50

age bet 10-20 20-30 30-40 40-50 50-60

age bet 10-20 20-30 30-40 40-50 50-60

GRAPH 5.2 SHOWING THE INCIDENCE OF HYPOTHYROIDISM A/C TO SEX.

RAPH 5.3: SHOWING THE INCIDENCE OF HYPOTHYROIDISM A/C TO

Graph 2 showing the incidence of hypothyroidism a/c to sex

6.25

93.75

0

10

20

30

40

50

60

70

80

90

100

male female

GOCCUPATION

Graph5.3 show ing the incidence of hypothyroidism a/c to occupation

, 56.25

, , , 21.87

,

,

, 18.75,

,

, ,

, 3.120

20

40

60

house w ife student sedentary w ork hard w ork

GRAPH 5.4 SHOWING THE INCIDENCE OF HYPOTHYROIDISM A/C TO SES.

RAPH 5.5 SHOWING THE INCIDENCE OF HYPOTHYROIDISM A/C TO DIET

0

20

40

60

upper middle class

middle class

low er middle class

poor

upper middle class middle class low er middle class poor

G

93.75

0

20

40

60

80

100

veg mixeddiet

GRAPH5.6 SHOWING THE INCIDENCE OF HYPOTHYROIDISM A/C TO F/H

Family history

01020304050

parents DM mother hypothyroid siblings hypothyroid daughter hypothyroid not associated

GRAPH 5.7 SHOWING THE INCIDENCE OF HYPOTHYROIDISM A/C TO P/H

depression/insomniahysterectomy

steroidsRA

not associated

0

5

10

15

20

RAPH 5.8 SHOWING THE INCIDENCE OF HYPOTHYROIDISM A/C TO GPRAKRITI

3.12 6.25

28.12

9.37 12.75

40.62

05

1015202530354045

vata predominent pitta predominent kapha predominentvatapitta vatakapha pittakapha

GRAPH 5.9 SHOWING THE INCIDENCE OF HYPOTHYROIDISM A/C TO SARA

34.37

46.87

18.75

0

5

10

15

20

25

30

35

40

45

50

twak mamsa medo

RAPH 5.10 SHOWING THE INCIDENCE OF HYPOTHYROIDISM A/C TO BMI G

3.12

37.5

59.37

0

10

20

30

40

50

60

below 20 20-25 above 25

GRAPH 5.11 SHOWING THE LEVELS OF TSH BEFORE AND AFTER TREATMENT:

020406080

100120140

BT AT

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16

RAPH 5.12 SHOWING THE SYMPTOAMTIC RELIEF PERCENTAGE

G

05

1015202530

BT ATwt.gain vertigo Easy fatigability lethargy cold intolerence hair lossslowness iof memory , anorexia constiaption gaseous distension voice changes mens.irregularitesoligo/amenorrhoea parasthesia muscle cramps muscle stiffness dry skin dull hairedema slow reflexes goiter

GRAPH 5.13 SHOWING THE OVER ALL RELIEF PERCENTAGE:

0

10

20

30

40

50

60

70

Over all relief percentage

Complete relief Marked relief Moderate relief Mild relief Norelief

Discussion

DISCUSSION

Hypothyroidism results when the thyroid gland produces less than

normal amounts of thyroid hormones. The result is the slowing down of many

bodily functions.

Since body has the ability to compensate for a failing thyroid gland

by increasing the stimulation to it, much like pressing down on the accelerator

when climbing a hill to keep the car going at the same speed. However as thyroid

hormone production decreases the body’s metabolism slows.

Hypothyroidism doesn’t have any characteristic symptoms. There

are no symptoms that people with hypothyroidism always have and many

symptoms of hypothyroidism can occur in people with other diseases.

Hypothyroidism is sometimes referred to as a "silent" disease because early

symptoms may be so mild that no one realizes anything is wrong.

Kanchanara Guggulu (Sa. Sam), a well-known Ayurvedic drug is

selected for this trail to evaluate its efficacy on hypothyroidism. The trail was

conducted on 32 patients from the Govt Ayurvedic Hosp, Erragadda; Analysis was

made to assess the results in relation to various factors.

It is a well-known fact that the disease Hypothyroidism is more

common in women than men, probably because hormonal imbalance acts as a

trigger for thyroid problems. Women’s bodies have a delicate balance of hormones

such as estrogen and progesterone, which can be upset when the body is under

stress and not receiving enough support. And also estrogens increases the

concentration of TBG and of total T3 and T4 levels. In the present clinical study

also out of 32 patients 30 were female and 2 of them were male.

Hypothyroidism 95

Discussion

Hypothyroidism can develop at any point in the life span. It is more

common in adults. In this clinical trail age incidence is high in the 2nd and 3rd

decades, 80% of the cases were found in this age group. It may be because the

medical Practioners and the patients are now more aware of this disease than in the

last few decades.

Actually the women, especially those older than 50, are more likely

to have hypothyroidism. But the symptoms of hypothyroidism are often subtle, or

people believe their symptoms are due to stress, depression, or "getting older," or

may frequently mistake for other conditions; it is not unusual for someone with

hypothyroidism to go undiagnosed, sometimes for many years. And also because

the symptoms of hypothyroidism and menopause are so similar, hypothyroidism

may easily be missed.

In the recent year’s peculiar changes in the cultural and social areas

forcing the human beings to arenas of tremendous stress. It is becoming more

prevalent in the modern society and upper socio economic classes. As thyroid

gland is one of the sensitive glands in the body it stimulates to stress easily the

incidence is high in this group. Whereas iodine deficiency hypothyroidism is

associated with lower/poor socio economic classes due to poor nutrition.

The disease is seen more in 1. Kapha prakriti predominents,

2.Mamsa, Medo sara predominants; 3. Non- vegetarians; 4. Those who consume

saturated fatty diet 5. People who takes rest for more than 10-15 hrs/day;

6. Whose BMI is above 20.

These all come under one umbrella ‘’the sedentary life style’’.

Heredity plays a role in both under active and overactive thyroid;

Recent studies show that 20% of the diabetic daughters area at the risk of

Hypothyroidism 96

Discussion

developing thyroid disorders. In the present trail 50% of the patients had a family

history of autoimmune disorders like DM, hypothyroidism, psoriasis etc.,

People with many autoimmune diseases have a higher risk for

hypothyroidism. One patient suffered from Rheumatoid Arthritis and Diabetes

Mellitus. Another patient was ASMA +ve (Anti Smooth Muscle Antibodies) with

chronic autoimmune hepatitis and Hasimoto’s Thyroiditis and Vitiligo. Another

was a case associated with Hyper Parathyroidism and Osteoporosis, Ca

supplement was added along with the trail drug.

Another case a 25 yr female c/o unable to attain menarche with

hypothyroidism diagnosed as turners syndrome with streak ovaries, she was

counseled properly as turners syndrome is highly impossible to treat and was

given treatment for hypothyroidism only.

Numerous medications can affect the thyroid. Some drugs given for

nonthyroid conditions have the side effect of inhibiting production of thyroid

hormone within the thyroid gland. If these drugs are taken in large dosages or for a

long time, hypothyroidism may result. Nitroprusside, lithium, or iodides in the

form of cough syrups, steroid and beta-blocker proponolol etc, and can induce

hypothyroidism.

Among the 32 patients 2 patients had a history of using steroids and

3 patients had a history of using medications for depression and insomnia, 2

patients had a history of using immunosuppressants. 6 patients had a history of

hysterectomy. It may be because hypothyroidism, in the early stages presents with

Menorrhagia, which may be easily misdiagnosed.

Another was a case of Juvenile Hypothyroidism, a 13 yr old boy

with a BMI of more than 38 (wt 78kilos) with typical dull expressionless face,

myxedamatous, thick, rough, cold doughy skin, hypercholestremia and delayed

Hypothyroidism 97

Discussion

DTR’s, deep slow voice and other symptoms. Unfortunately the case was a drop

out.

The TSH levels became normal in the fresh 16 cases, in 2 patients

after with drawl of the drug no recurrence is noted even after 6months. In the

chronic cases that are already using the allopathic drug Thyronorm the drug was

gradually replaced with the trail drug. The TSH levels were maintained during the

replacement time. 4 patients were advised to continue the medication along with

the allopathic drug, as they are at the perimenopausal stages, and the chronicity of

the disease is high.

Coming to the results, 33% of relief was observed in those who

complained of weight gain or unable to loss weight. Good results were observed

in the fresh cases and who exercised regularly. But in the chronic cases that were

habituated to sedentary life style no significant results were observed. In the

patients who got relief there was 4/5 kilo of weight loss was observed in the three

months duration. Exercise is especially important for weight loss among

hypothyroidism sufferers.

Menstrual irregularities are the main symptom in hypothyroid

patients, which brings them to the hospital. In among the 32 patients 50% of the

patients complained of menstrual irregularities, most of them also complained of

oligomenorrhoea. 87.5% relief was observed in these cases. In 2 patients who

complained of infertility one had altered FSH levels and Anovulatory cycles,

another patient complained of repeated abortions. In both of these patients

infertility was not relieved in 3 months durations of the course.

Another main symptom constipation, poor appetite, gaseous

distention was 95% relieved after the treatment, as the all the ingredients in the

trail drug acts as Deepana and Pachana.

Hypothyroidism 98

Discussion

Vertigo, mood disturbances, easy fatigability, tiredness, lethargy,

slowness of memory, intellect and thought were the early symptoms and marked

relief was observed in these symptoms.

Parasthesia’s, muscle cramps, weakness, muscles stiffness and

aching were the main complaints of the chronic cases. 50-60% of relief was

observed in these cases, as Guggulu acts as anti-inflammatory and analgesic.

15 patients complained of occasional voice changes like hoarseness;

slowness of voice etc. 66% relief was noted. Hair loss was seen in 18 patients and

60% of relief was observed in these cases. Dry, rough skin is seen in 70% cases

and half of the patients got relief. 35% of cases showed dry, brittle, lusterless hair.

Brittle nails, recurrent attacks of infections were observed in many patients. 85%

of the cases showed significant improvement in puffiness of the face, feet and

palms.

One patient’s only complaint was chronic rhinitis.

Cardiac and respiratory symptoms are rarely observed in 32 patients.

One patient aged 65yrs with Bradycardia, Cardiomegaly was seen. But it was

under exclusion criteria.

Goiter was seen in 11 cases, the trail drug showed effective in acute

and grade I Goiter. No significant results were observed in chronic cases. In one

case of euthyroid and MNG (multi nodular goiter) since 6yrs, the recent nodule

noted 3months back was reduced and other nodules become soft in consistency in

the duration of 3 months.

Thinning of the lateral thirds of the eyebrows (Queen Anne’s sign)

was noticed in one patient.

Hypothyroidism 99

Discussion

Complications:

During the replacement of the allopathic drug puffiness of the face,

mood disturbances, feeling of heaviness, muscle cramps were noted in 4 patients.

But it was adjusted by increasing the dosage of the trial drug.

Gastritis was another complaint seen in 2 patients, but it was

negligible and was controlled after minimizing the dosage of Kanchanara

Guggulu.

Hypothyroidism 100

Conclusion

CONCLUSION

1. As the symptoms of hypothyroidism vary widely, and its clinical features

mimics that to many other diseases, so it is often remains undiagnosed or

misdiagnosed.

2. Clinical features for hypothyroidism are notorious, so it remains in the

individuals without even diagnosed.

3. The incidence of hypothyroidism is seen in those with a family history of

autoimmune disorders, history of autoimmune disorders, previous

medication of antidepressants, steroids etc, those who adopt sedentary life

style.

4. The incidence is high in females compared to males, may be probably due

to hormonal imbalance triggers the disease.

5. Of the blood tests for hypothyroidism, the TSH is the most sensitive and

best test for hypothyroidism. The normal range of TSH is 0.30-5.5uIU/ml.

If the TSH level is above 6, then a diagnosis of hypothyroidism was made.

But most people feel best when their TSH level is between 0.5 and 2.5.

6. But FT4 is the accurate diagnosis for the disease.

7. The trail drug Kanchanara Guggulu and Shigru Patra Kwatha is found to be

beneficial in recently diagnosed cases.

8. Mild to moderate relief was noted in patients who are already using the

drug thyronorm and it can be completely replaceable with the trail drug

depending upon the rogi bala and rogibala. TSH levels and the clinical

features should be carefully monitored.

Hypothyroidism 101

Conclusion

9. The patients who are in perimenopausal or menopausal stages, who has a

chronicity of more than 10yrs, who has a history of autoimmune disorders

it would be advisable to continue the medication along with the thyronorm.

10. Further research is recommended in

i) The patients who are allergic to Guggulu.

ii) The patients suffering from complicated symptoms like

bradycardia, cardiomegaly, sleep apnea etc.

iii) In pregnant and elderly

11. Further drug research need to be done

i) Thyroid stimulatory drugs

ii) Iodine rich drugs

iii) Selenium containing drugs or helps in absorbing Se like Pippali

etc.

iv) Immuno modulator drugs useful in AITD’s.

12. It will be very beneficial if we can exactly correlate the disease

hypothyroidism in Ayurveda.

Hypothyroidism 102

Summary

SUMMARY

In Part I:

• Importance of the disease hypothyroidism in present days and criteria for

selection of the disease was described in the chapter Introduction.

• History of hypothyroidism from the beginning of endocrinology to modern

days was described in the chapter Historical aspect of Hypothyroidism.

• Anatomy, physiology of the thyroid gland and the role of iodine was

described in the shareera.

In Part II:

Disease review was explained under sub heads

• Nidana of hypothyroidism the etiological factors of hypothyroidism

primary, secondary and tertiary hypothyroidism and their causes were

explained.

• In Samprapti, pathogenesis of the disease iodine deficiency

hypothyroidism, Autoimmune Thyroid Diseases were explained.

• In Rupa of the disease, the clinical features of the hypothyroidism

according to the systemic manifestation of the disease were explained.

• Lakshanika Samprapti the effects of decreased thyroid hormone and how

they cause different symptoms and pathological changes in different

systems was explained.

• Galaganda as explained in the Ayurvedic classics was described.

Hypothyroidism 103

Summary

• Investigations for hypothyroidism: Estimation of T3, T4, TSH, FT4, FT3,

ultrasound, FNAC, etc were explained.

• Complications of hypothyroidism: goiter, heart problem, myxedema

coma were the main complications for hypothyroidism.

• Goiter and its types were explained in this chapter.

• Ayurvedic Concept of Hypothyroidism including Galaganda,

Agnimandya etc. were explained.

• Sadhyasadhyata of Hypothyroidism explained as per the causes of

Hypothyroidism.

In part III

• Chikitsa yojana: The chikitsa of hypothyroidism, the thyroid stimulators,

immuno modulators, iodine rich drugs, deepana, pachana drugs were

discussed here.

• Pathyapathya the ahara and vihara’ s which are suitable and non suitable

for the patient were described.

In part IV

• Drug review: The drug Kanchanar Guggulu and Shigru Patra Kwatha were

selected for clinical study, were described here.

In part V

• Material and methods: materials required for the study were the patients,

drug. Both subjective and objective parameters were taken into

consideration. The dosage of the drug was 250mg b.d and 200ml of Shigru

patra kwatha. The duration of the treatment was 3months.

Hypothyroidism 104

Summary

• Observations: The conditions of the patient were observed carefully and

the data was analysed carefully.

• Results: Based on the observations made the results are assessed. The

results are assessed as complete relief, marked relief, moderate relief, mild

relief, and no relief from the clinical features of the disease.

• Discussion and conclusion: disease, drug aspects observations and results

are discussed elaborately on various angles. From this the conclusions are

drawn.

In Appendices

• Bibliography, Case sheet, and BMI chart were included.

Hypothyroidism 105

References

REFERENCES

1. A SHORT HISTORY OF MEDICINE, Singer C, Underwood EA.

a. 2nd Ed, oxford, oxford university press, 1962.

2. A HISTORY OF ENDOCRINOLOGY, Hudhes AF, journal of the history of medicine and allied sciences, 1977

3. PRINCIPLES OF ANATOMY AND PHYSIOLOGY; Gerard J Tortora, Harper

& ROW publications, 1984.

4. Grays text book of anatomy-Henry gray

5. Clinically oriented anatomy

6. Human physiology by C.C. CHUTTERJEE, medical allied agency, Calcutta,

1988.

7. Endocrine Pathophysiology Hershman, J.M; lea and fibriger, 1998.

8. Applied Physiology –By best And Taylor.

9. Clinical guide to nutrition and dietary supplements in disease management,

Jennifer R. Jamison. Churchill Livingston, 2003

10. Robbins Text book of pathology –Robbin

11. Current Medical Diagnosis and Treatment.

12. Principles of internal medicine-Harrisons-12th ed 1991

13. Essential endocrinlogy By Charles Brooks,Nicholas marshall; Blackwell series,

3rd ed.

14. A clinical hand book of endocrinology and metabolic disesases by Neil I Robin,

partheton publications, 1995.

15. Clinical Endocrinolgy And Diabetis, Edited by michel C. Shepard and Gayne A

franklyn, Pub: Churchill Livingston 1988.

16. Essential Endocrinology by Oxford University Press, 1966.

17. Human Endocrinology by Paul R. GUARD, Taylor and Francis, 1988

18. Oxford Hand Book Of Endocrinology And Diabetis by Turner, Helen, Wass,

John., Oxford U.P, 2001

Hypothyroidism

References

19. Essential Endocrinology by John F. Leycock, Peter H Wise, OXFORD

UNIVERSITY PRESS.1999

20. Endocrinology by Andrew lewy, Stafford lightman, Oxford university press,

1997.

21. Endocrinology by Martin Hartog , Blackwell Scientific, 1987.

22. Diagnostic tests in endocrinology and diabetis; Ed-By P-Boulax and LH Brooks.

23. Text book of surgery by Das, Dr.S.Das, calcutta2001.

24. Sarangadhara Samhita

25. Astanga Hridayam V.Ramaswamy and sons. Madras, 1954

26. Bhava Prakasa; mukkamala venkata sastry, Panduranga printing works,VJA.1959

27. Charaka samhita ; agnivesa, V.Ramaswamy and sons. Madras.

28. Nighnatu Adarsh- Bapalal G Vaidya, Choukhambha Bharathi academy.Varanasi.

29. Indian medicinal plants, Kirtikar and Basu; Jayyed press, Delhi, 1975.

30. Susrutha Samhita by Ambika Datta Sastry, Choukhambha samsthan. Varanasi.

31. Kashyapa Samhita

32. www.ayurvedaforu.com

33. Clinical researches by Dr.Tripati & others

34. Dravyaguna vignana by J.L.N.Sastry.

Hypothyroidism

BIBILOGRAPHY

1. A short History of Medicine, Singer C, Underwood EA, 2nd edition;

Oxford, Oxford university press.1962.

2. A History of Endocrinology, Hudhes AF, journal of the history of medicine

and allied sciences.

3. Applied physiology by Best and Taylor.

4. A Clinical Hand book of Endocrinology and Metabolic Diseases By Neil I

Robin, Partheton Publications, 1995.

5. Astanga sangraham, V Rangacharyulu. Telugu academy Hyd. 1979

6. Astanga Hridaya V Ramaswamy and Sons, Madras, 1954.

7. Bhava Prakasa, Mukkamala venkata sastry, Panduranga Printing Works ,

VJA, 1959.

8. Bhava prakasha nighantu, Dr Krishna Chandra Chunekar, Choukhambha

Sanskrit sansthan, varanasi, 5th ed 1959.

9. Bhaishajya kalpana, dr k nisteswar, AP Ayurved Literature Improvement

Trust.

10. Bhaishajya Ratnavali, Ambika Datta Sastry, 1969,

11. Bhela samhita, SVS Sastry, CRR sarma, CCRIM&H, New delhi, 1977.

12. Charaka samhita, Agnivesha, V Ramaswamy and sons, Madras.

13. Clinically Oriented Anatomy

14. Clinical Guide to Nutrition and Dietary Supplements in Disease

Management, Jennifer R Jemison, Churchill Livingston 2003.

15. Concept of Ama in Ayurveda, Dr M Srinivasulu, Chaukhambha Sanskrit

series, Varanasi, 2005.

16. Concept of Agni in Ayurveda, Bhagvan Das, Chaukhambha Sanskrit series,

17. Compendium of Indian Medicinal plants By Ram P Rastogi, BN Mehrotra,

Central Drug Research Institute, Lucknow.

18. Current Medical Diagnosis and Treatment,

19. Clinical Endocrinology and Diabetis, Edited By Micheal C Shepeard and

Gayne A Franklyn Publications, Churchill Livingstone, 1988.

20. Diagnostic tests in Endocrinology and Diabetis, Ed by P Boulax and LH

Books.

21. Digestion and metabolism in ayurveda.C Dwarakanath, Vaidyanath

Ayurved Bhavan, 1947.

22. Dravyaguna Vignanam By K Nisteswar, AP Literature Improvement Trust.

23. Dravyaguna Vignan by JLN Sastry, Chaukhambha Sanskrit series.

24. Endocrine Patho Physiology, Hershman, JM Lea and Fibriger, 1998.

25. Essential endocrinology Charles Brooks, Nicholas Marshal, Blackwell

series, 3rd Ed.

26. Essential endocrinology by Oxford University Press, 1966.

27. Essential endocrinology by John f Leycock , Peter H Wise, Oxford

University Press. 1999.

28. Essentials of Medical Pharmacology, KD Tripathi, Jaypee Publications, 4th

ed, 1999.

29. Essential Pediatrics, OP Ghai, Interprint Publications.

30. Endocrinology by Andrew lewy, Stafford lightman, Oxford University

Press , 1997.

31. Endocrinology by Martin Hartog, Blackwell Scientific, 1987.

32. Gray’s textbook of anatomy Henry Gray.

33. Human physiology by CC Chuttarjee. Medical allied Agency, Calcutta,

1988.

34. Human Endocrinolgy by Paul R Guard, Taylor and Francis, 1988.

35. Harita samhita by harita, Sri Venkateswara Press, 1849.

36. Indian medicinal plants, Kirtikar and Basu, Jayyed Press, Delhi, 1975.

37. ICMR, Medicinal Plants of India, 1976.

38. Indian Material Medica, Nadkarni.

39. Kashyapa Samhita, Pt Hemaraj Sharma, Choukambha Sanskrit Series,

Varanasi.

40. Madhava Nidana, Sri Yadundanopadhyaya, Choukambha Sanskrit Series,

Varanasi.

41. Nighntu Adarsh, Bapalal G Vaidya, Choukambha Sanskrit Series, Varanasi.

42. Oxford handbook of endocrinology and Diabetes by Turner Helen Wass,

John, Oxford University Press, 2001.

43. Principles of Anatomy and Physiology Gerard J Tortora, Harper and Row

Publications, 1984.

44. Principles of Internal Medicine, Harrisons 12th ed 1991.

45. Robbins text book of pathology, Robbin

46. Sarangadhara Samhita, Sarangadhara, Vavilla Ramaswamy and sons, 1952.

47. Shabda Sthoma Mahanidhi, Sri Daranath, Takravachaspathi Bhttacharya,

Vidanyantara press, Calcutta 1976.

48. Susruth Samhita, Ambika Datta Sastry, Choukambha Sanskrit series,

Varanasi.1954.

49. Textbook of Surgery by Das, Dr. S das, Calcutta 2001.

50. Priciples of practice and medicine by Davidson, 17th ed.

51. Yoga Ratnakram by Yeturu Srinivasacharyulu, Nellore, 1939.

PATIENT CONSENT FORM

I____________________________________________________

exercising my free power of choice, hereby give you my complete consent to be

included as a subject in the Clinical trial on "A CLINICAL STUDY ON THE

EFFECT OF KANCHANARA GUGGULU AND SHIGRU PATRA

KWATHA ON HYPOTHYROIDISM". I have been informed to my

satisfaction by the attending Doctor, the purpose of the Clinical Trial and the

nature of drug treatment, follow-up and probable complications. I am also ready

to undergo necessary Laboratory Investigations to monitor and safeguard my

body functions.

I am also aware of my right to opt out of the trial at any time during the

course of the trial without having to give the reasons for doing so.

Signature of the Doctor Signature of the Patient / Guardian (Dr.VVL Prasuna)

vi

Post graduate department of Kayachikitsa Dr. BRKR Govt. Ayurvedic College

HYDERABAD

Special case sheet for hypothyroidism

Serial no:

Date: Occupation:

Name: Marital status:

Age: Socio economic status:

Sex: Address:

1. Chief complaints and duration:

2. Associated symptoms:

3. History of Present illness:

4. History of Previous illness:

5. Personal history:

6. Family history:

7. Present/ Previous drug history:

8. Astha sthana pariksha: 1. Nadi: 5. Sabda:

2. Mutram: 6. Sparsha:

3. Malam: 7. Drik:

4. Jihwa: 8. Akriti:

9. Dasavida pariksha:

1. Prakriti: 6. Vayah:

2. Vikriti: 7. Satwam:

3. Sara: 8. Satmyam:

4. Samhanana: 9. Ahara sakti:

5. Pramana: 10. Vyayama sakti:

10. Vikriti pariksha: 1. Nidana:

2. Purvarupa:

3. Rupa:

4. Upasaya:

5. Samprapti:

11. General examination: 1. BMI: 2. CVS: 3. Nervous system: Reflexes: Rt: Lt: UL: 1. Biceps: 2. Triceps: 3. Supinator: LL: 1. Knee jerk: 2. Ankle jerk: 4. Skin& hair: 5. Thyroid:

12. Clinical study (subjective parameters):

Symptoms

Before Tt Dt:

During Tt Dt:

During Tt Dt:

After Tt Dt:

Genl:

1.Vertigo

2.Wt. gain

Neuro muscular:

3.easy fatigability

4. lethargy

5.Myalgia

6. GI disturbances:

poor appetite:

Constipation:

7. Dermatological:

8. Menstrual

irregularities

9. Speech

disturbances:

10. Others if any

14. Objective parameters:

Investigations:

Before Tt Dt:

After Tt Dt:

Thyroid profile: 1. T3 2. T4 3. TSH

15. Observation:

14. Result: 1. Cured:

2. Partially cured:

3. No response

Signature Signature Signature P.G.Scholar co-supervisor supervisor