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Thyroid GlandThe metabolism of Virtually all nucleated cells of many tissues in the body is controlled by thyroid hormone

Over activity (Hyperthyroidism) and under activity (Hypothyroidism) of the gland are most common of all endocrine problems

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Thyroid GlandAnatomy:

It has two lateral lobes connected by Isthmus

It moves on swallowing as it is attached to thyroid cartilage and trachea

Embryologically it originates from the base of the tongue and then descends therefore sometimes remnants of thyroid can be found at the base of tongue (Lingual thyroid)

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Thyroid GlandAnatomy:

Thyroid gland has follicles lined by cuboidal epithelial cells. Inside the follicle is colloid (Iodinated glycoprotein Thyroglobulin) which is synthesized by follicular cells.

Each follicle is surrounded by basement membrane, between follicular cells there are parafollicular cells containing calcitonin secreting C cells

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Follicular & parafollicular cells

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Thyroid GlandPhysiology:

Thyroid gland synthesizes two hormones T3 – Triiodothyronin: acts at Cellular level

T4 - L – Thyroxin: which is prehormone

More T4 is produced than T3 in thyroid but T4 is converted to T3 in periphery

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Thyroid Gland

Physiology:In Plasma more than 99% of T4 and T3 is

bound to protein (Thyroxin Binding Globulin TBG, Thyroid Binding PreAlbumin TBPA) and Albumin

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Thyroid GlandPhysiology:Control of hypothalamic–pituitary–thyroid axis:Hypothalamus produces TRH – Thyrotropin releasing hormone, it stimulates pituitary to secrete TSH – Thyroid Stimulating Hormone.TSH stimulates activity of Thyroid Follicular cells T3 & T4 are secreted in circulation by follicular cellsT3 & T4 has negative feedback effect on Hypothalamus and pituitary

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Physiological Effect of Thyroid Hormone

Thyroid GlandThyroid Function Test:

Free T4 Free T3 and TSH are available and test can be done at anytime of the day

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1 Thyrotoxicosis ↓TSH Free T4 ↑ Free T3 ↑

2Primary

HypothyroidismTSH ↑

Free T4 ↓Or Low Normal

T3 N or Low

3TSH Deficiency

(Pituitary) ↓TSH

Free T4 ↓ or Low Normal

T3 N or Low

HYPOTHYROIDSM

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HypothyroidismIt is usually primary due to disease of thyroid, but may be secondary to hypothalamic – pituitary disease (decreased TSH drive)

It is more common in females

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HypothyroidismAutoimmune Hypothyroidism

It is most common cause and associated with antithyroid antibodies

It is six time more common in females

It has association with other autoimmune diseases e.g. pernicious anemia, Vitiligo etc.

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HypothyroidismHashimotos Thyroiditis

This is a form of autoimmune thyroiditis, more common in females and occurs in late middle age

Causes atrophic changes and regeneration leading to goiter formation

TPO ( Thyroid per oxidase) antibodies are present in high titer (> 1000 IU/L)

Patient may be hypothyroid or Euthyroid, though they may go through initial toxic phase

Levothyroxin is given when patient is hypothyroid

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HypothyroidismPost Partum Thyroiditis

This is transient phenomena, observed after pregnancy

It may cause Hyperthyroidism, Hypothyroidism

It is due to result of modifications to the immune system in pregnancy

It is usually self limiting or leads to hypothyroidism

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Defects of Thyroid Hormone SynthesisDefects of Thyroid Hormone SynthesisIodine Deficiency

Iodine is required for synthesis of T3 & T4

We take iodine in diet, if deficient than people get goiter ( due to TSH stimulation)

Patient may be euthyroid or hypothyroid Iodine deficiency is problem in many

countries e.g. Netherlands, India, Asia, Africa, Russia

Efforts are made to prevent iodine deficiency by adding iodine in common salt. 17

Defects of Thyroid Hormone SynthesisDefects of Thyroid Hormone SynthesisDyshormonogenesis

Rare condition, due to genetic defect in the synthesis of thyroid hormone

Patient develops hypothyroidism with goiter

Note—Some people have Genetic defect causing sensorineural deafness due to mutation at chromosome 7, they have goiter( hypothyroid) also and this condition is called Pendred Syndrome

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Hypothyroidism Symptoms and Signs

*Bold type indicate important symptoms and signs

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Hypothyroidism

HypothyroidismHypothyroidismMyxoedema:

It refers to Hypothyroidism plus accumulation of mucopolysaccharide in subcutaneous tissue

Patient is slow, thick skin, dry hair, deep voice, weight gain, cold intolerance, bradycardia, constipation

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HypothyroidismHypothyroidismChildren with Hypothyroidism:Have slow growth velocityHave poor school performance

Young Females with HypothyroidismHypothyroidism should be excluded

in all women with Oligomenorrhoea, amenorrhoea, menorrhagia, infertility, Hyperprolactinimia

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HypothyroidismHypothyroidismInvestigations:

Serum Free T3, Free T4 and TSH High TSH confirms primary

Hypothyroidism, free T4 is low Other investigations:

Anemia – usually normocytic normochromic

But may be Macrocytic (due to associated Pernicious anemia )

Microcytic – in women due to menorrhagia

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HypothyroidismHypothyroidismOther Investigations:

Increase serum creatinine Kinase – with associated Myopathy

Hypercholesterolemia and hypertriglyceridaemia

Hyponatremia – due to increase ADH

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HypothyroidismHypothyroidismTreatment:

Thyroxin – T4 is given for life Dose 100 Micrgram daily for young patients 50 microgram for small, old patient to be

increased to 100 microgram after 2 – 4 days If patient has IHD start with 25 Microgram

daily and increase dose at 3 – 4 week interval ( monitor by serial ECG)

Aim of treatment is to restore T4 & TSH within normal range

Improvement on T4 takes 2 weeks or more and resolution of symptoms takes about 6 months

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HypothyroidismHypothyroidismTreatment for Myxoedema:

It is severe hypothyroidism and patient may present with confusion or even COMA

Myxoedema Coma is very rare, hypothermia is often present and patient may have severe cardiac failure, pericardial effusion, hypoventilation, hypoglycemia, hyponatremia

Mortality is high26

HypothyroidismHypothyroidismTreatment for Myxoedema:

T3 orally or IV 2.5-5 microgram 8 hourly

O2 Hydrocortisone 100 mg IV 8 HourlyGlucose infusionGradual rewarming

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HyperthyroidismHyperthyroidism (Thyrotoxicosis) is common,

affecting 2-5% of all females Female-Male ratio 5:1 Age 20-40 years More than 99% cases are caused by intrinsic

thyroid disease, pituitary cause is extremely rare

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Graves DiseaseThis is most common cause of hyperthyroidism

and is due to autoimmune process IgG antibodies bind to TSH receptors in the

thyroid and stimulate thyroid hormone production (IgG behaves like TSH)

TSH receptor antibodies (TSHR – Ab antibodies) are specific for Graves Disease

Graves Disease is associated with autoimmune disorders such as pernicious anemia, Vitiligo and myasthenia gravis

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Other Causes of Hyperthyroidism/ThyrotoxicosisSolitary toxic adenoma/nodule It is cause of 5% cases of hyperthyroidism usually

remit after antithyroid drugs Toxic multinodular goitreCommonly occurs in older womanAnti thyroid drugs control hyperthyroidism

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Other Causes of Hyperthyroidism/ThyrotoxicosisDe Quervain’s thyroditis This is transient hyperthyroidism due to

inflammatory process, probably viral in origin

There is fever, maliase, pain in the neck, tachycardia and local thyroid tenderness

Thyroid function test show - Hyperthyroidism - Increased ESR 33

Other Causes of Hyperthyroidism/ThyrotoxicosisDe Quervain’s thyroditis Thyroid function test show (cont) - Thyroid uptake show suppression of uptake in

acute phase - Hypothyroidism, usually transient, may follow

after few weeks Treatment of acute phase - Aspirin - Predinisolone

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Other Causes of Hyperthyroidism/ThyrotoxicosisAmiodarone – induced thyrotoxicosis (AIT)Amiodarone is anti arrhythmic drug – class

111 and causes hyperthyroidism

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Symptoms and Signs of Hyperthyroidism

36*Bold type indicate important symptoms and signs

Clinical Features of HyperthyroidismThe eye signs of lid lag and stare May occur with hyperthyroidism of any cause Graves dermopathy Pretibial myxoedema – is in filtration of the skin

on the shin Thyroid Acropachy – very rare and consist of

clubbing, swollen fingers and periosteal new bone formation

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Clinical Features of Hyperthyroidism (cont)

Atrial Fibrillation in the elderly Is frequent presentation Children with hyperthyroidism May present – excessive height,

hyperactivity

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Pretibial myxoedema

Differential Diagnosis Anxiety (Sympathetic Stimulation) There is tachycardia, tremor, but cold

clammy hand

In hyperthyroidism, there is tachycardia tremor, warm hands, eye

signs, diffused goitre, weight loss despite increase appetide

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Hyperthyroidism InvestigationsSerum TSH is suppressed, free T4 or T3 are

raised Thyroid per oxidase (TPO) and thyroglobulin

antibodies are present in most cases of Graves disease

Thyroid stimulating immunoglobulin (TSI) are present in Graves disease

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HyperthyroidismTreatmentThree options are available 1. Anti thyroid drugs 2. Radio active iodine 3. Surgery

1. Anti thyroid drugs Carbimazole – 20-40mg/day 8 hourly or single dose Propylthioracial (PTU) – 100-200mg 8 hourly They inhibit the formation of thyroid hormonesPropranolol (Beta Blocker) is used for symptomatic relief

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HyperthyroidismTreatmentSide effects of drugs Carbimazole – rash, nausea, vomiting,

arthralgia, agranulocytosis, jaundice PTU – rash, nausea, vomiting, agranulocytosis NOTE – As agranulocytosis is the side effect,

therefore, patient is advised if he has sore throat, he should report to hospital for investigation

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HyperthyroidismTreatment (cont)2. Radioactive Iodine – 131Iodine Can be given to all patientsIs contraindicated in pregnancy and during

breast feeding3. SurgerySubtotal thyroidectomy/thyroidectamy Side effects – laryngeal nerve palsy occur in 1%Transient hypocalcemia up to 10%

Permanent hypoparathyroidism < 1%

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Hyperthyroidism in PregnancyDuring pregnancy Propylthioracial (PTU) is

preferred because there are reports of congenital abnormalities with Carbimazole

TSI – thyroid stimulating immunoglobulin cross the placenta and stimulate fetal thyroid

Carbimazole and PTU cross the placenta T4 (Thyroxin) very poorly crosses the placentaIf necessary surgery can be performed in

second semester of the pregnancy

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