Anatomy & physiology of thyroid gland

SURJEET ACHARYA

Thyroid gland -anatomy

Size : Lobes :5cm x 2.5cm x 2.5cmIsthmus: 1.2cm x 1.2 cm

Weight: 25g

Capsules of thyroid gland

True fibrous capsule

False fascial capsule

Suspensory ligament of Berry

On deglutation

Thyroid to hyoid –thyrohyoidThyroid to cricoid –cricothyroid

When mylohyoid contracts – hyoid pulled up

Parts & relations

• An Apex

• A Base

• 3 Surfaces : Lateral, Medial, Posterolateral

• 2 Borders : Anterior and Posterior

Arterial supply

Thyroid imaartery

Venous drainage

Tubercle of zuckerkandl

Nerve supply

Lymphatics

Histology

Large no of closed follicles

- Filled wit colloids- Lined by cuboidal

cells- Major constituents

– thyroglobulins Blood flow 5times

the weight

Physiology of thyroid gland

• Formation and Secretion of thyroid hormones –T3 & T4

• Metabolic Functions

• Regulation of their hormones

Steps in synthesis

• Iodide trapping

• Oxidation of Iodide ion

• Organification of thyroglobulin

• Coupling of Iodotyrosine residues

• Release of T3 & T4 into blood

Daily rate of secretion of hormones

• Thyroxine – 93%

• Triiodothyronine – 7%

• 1/4th of T4 deiodinated to additional T3

• Hormones delivered & used by tissues as T3

Transport of T3 & T4

• Bound to plasma proteins – TBG, TBPA & albumin

• Released slowly to tissue cells because of high affinity to plasma proteins ( T4 – 6 days, T3 – 1 day)

• Binds with intracellular proteins, stored in target cells, released slowly over periods

• Slow onset & long duration of action

Metabolism and excretion

• Intracellular thyroid hormone receptors high affinity to T3

• Before acting on target cells, deiodinase (D1&D2) enzymes remove one iodide from most of T4

• D3 responsible for inactivating T3 and preventing activation of T4 by converting it into RT3

• After inactivation, T3 conjugated with sulfates & glucuronides, excreted in bile, partially reabsorbed after deglucuronidation in intestines

• Effect on cellular metabolic activity

- Increases number & activity of mitochondria

- Increases active transport of ions through cell membranes

• Effect on other endocrine glands

- Controls rate of secretions of other glands

• Effect on sexual function

- Promotes normal functioning

Functions of TSH Increased proteolysis

of Tg Increased activity of

iodide pump Increased iodination

of tyrosine Increased size &

secretory activity of thyrois cells

Increased number of thyroid cells

THYROTOXICOSIS

THYROTOXICOSIS& HYPERTHYROIDISM

• Thyrotoxicosis- Symptom complex due to raised levels of thyroid hormones

• Hyperthyroidism- Thyrotoxicosis due to overproduction of thyroid hormones by the thyroid gland

• Hyperthyroidism is one of the causes of thyrotoxicosis

• Thyrotoxicosis can occur due to causes other than hyperthyroidism

HYRERTHYROIDISM

• Primary thyrotoxicosis – Graves disease, exophthalmic goitre, diffuse goitre (Basedow’sdisease)

• Secondary thyrotoxicosis – Secondary to multinodular goitre (Plummer disease)

• Tertiary thyrotoxicosis – Solitary toxic nodule –Autonomous nodule not under control of TSH but due to hypertrophy and hyperplasia of the gland (Goetsch’s disease)

RARE CAUSES

• Thyrotoxicosis factitia – drug induced- L thyroxine• Jod Basedow thyrotoxicosis – because of large doses of

iodides given to a hyperplastic endemic goiter• Autoimmune thyroiditis or de Quervain’s thyroiditis• Neonatal thyrotoxicosis• Struma ovarii• Drugs like amiodarone- an antiarrhythmic agent. Amiodarone

is rich in iodine having structural similarity to T4 causing thyrotoxicosis

• Well differentiated carcinoma can cause thyrotoxicosis-metastatic type

• Hydatidiform mole or choriocarcinoma with high levels of ß HCG can stimulate TSH receptor- thyrotoxicosis

GRAVES DISEASE

• Most common cause of hyperthyroidism

• Named after Irish physician Robert Graves

• Also referred as Basedow’s disease after Karl von Basedow who also described cases

• Autoimmune disease with TSH receptor antibodies in blood

`

• TSI/TsAb and LATS cause pathological changes in thyroid

• Histologically acinar cell hypertrophy and hyperplasia with absence of normal colloid in the tall columnar epithelium

• Familial

• Puberty, pregnancy, emotion and infection –precipitating factors

TOXIC ADENOMA

• Benign functioning monoclonal thyroid tumour

• Solitary nodule of thyroid

• Autonomous functioning tumour; not TSH responding

• Secretes large quantity of thyroid hormones suppressing the function of remaining normal thyroid tissue

• No eye signs and other features of Graves disease

• Higher T3 levels than T4

• TSH receptor or G protein- somatic mutation

• USG, T3,T4, TSH, Radioisotope scan (hot nodule)

T3 TOXICOSIS

• T3 alone is raised

• TSH decreased

• T4 normal

• Free T3 estimation is important

SUBCLINICAL HYPERTHYROIDISM

• Decreased TSH level but not undetectable with T3, T4, free T3, free T4 are within the normal range without any clinical symptoms

• Its incidence is 1% of hyperthyroidism

• Cause of infertility in females

• May present as cardiomyopathy or arrhythmias

• Hormone assay, radioisotope scan and US neck, ECG

STRUMA OVARII

• Ovarian teratoma with thyroid differentiation will secrete T3, T4 and suppress TSH

• Function of normal thyroid in neck is suppressed

• Radioisotope scan shows uptake in pelvis with no or less uptake in neck

HASHITOXICOSIS

• Due to autoimmune Hashimoto’s thyroiditis

• Mild toxic features develop during initial stage of hyperplasia

• Already formed thyroid hormones are released by inflamed gland causing toxicity

HYPERTHYROID EUTHYROID HYPOTHYROID

THYROTOXICOSIS FACTITIA

• Intake of L thyroxine without indications to lose weight

or

• Overdose intake of L thyroxine

Causing toxicity

Postpartum hyperthyroidism

• Exacerbation of previously confirmed or undiagnosed hyperthyroidism during pregnancy due to increased autoimmune factors

• It is associated with HLA DR3 and HLA DR5

NEONATAL THYROTOXICOSIS

• In infants born to mother with Graves disease due to crossing of the thyroid stimulating antibody across placental barrier

• Infant will be toxic for 3-4 weeks which subsides gradually

TROPHOBLASTIC THYROTOXICOSIS

• HCG secreted from vesicular mole, choriocarcinoma or metastatic embryonalcarcinoma in females, acts like TSAb causing toxicity

Jod basedow thyrotoxicosis

• Patient with hyperplastic endemic goitre takes large doses of iodine, taken up by hyperplastic gland in large quantity causing temporary hyperthyroidism

• It differs from Basedow disease (Graves disease)

Apathetic hyperthyroidism

• Lacks all usual clinical features of toxicity

• Old people

• Thyroid gland is not enlarged

• Behavioral problems

• Recent angina or atrial fibrillation

• Diagnosis is masked

Subacute thyroiditis

• A destructive release of preformed thyroid hormone

• Radioactive iodine uptake in the thyrotoxicphase of the disease

• Thyroid hormone levels can be highly elevated

• Low ESR, low T3 T4 ratio

Clinical Features of Thyrotoxicosis

HISTORY ?

BEFORE SUBJECT PROPER….

• An 11-year-old female with no significant past medical history presented with symptoms like weight loss and heat intolerance.

• She has also experienced a decline in grades at school.

• Family history is significant for thyroid disease in both grandmothers (both on thyroid replacement therapies).

• The clinician ordered thyroid function tests ; – Free T4, T3, TSH, anti-TSH receptor antibodies,

antithyroglobulin and antithyroid peroxidase antibodies.

• The results for the tests follow:– Free thyroxine (FT4)2.87 ng/dL (Increased)

– Triiodothyronine pediatric (T3)374.00 ng/dL(Increased)

– Thyroid-stimulating hormone (TSH) <0.018 uU/ml (Decreased)

– Thyroxine (T4)18.2 ug/dL (Increased)

– Antithyroglobulin antibodies >3000 IU/ml (positive)

– Antithyroid peroxidase antibodies2667 IU/mL (Positive)

– Anti-TSH receptor antibodies 69.6 % (Increased)

Diagnosis

Graves's disease

(hyperthyroidism with thyrotoxicosis)

* http://path.upmc.edu/cases/case537.html

Contributed by Anca V. Florea, MD and Mohamed A. Virji, MD, PhD

Objectives

• To elaborate on Clinical features in a patients with THYROTOXICOSIS.

– Symptoms

– Signs

• Eye signs

• Cardiac Manifestations

• Myopathy

• Pretibial Myxoedema

• Thyroid acropathy

• Other features

Symptoms

Goitre

Primary Thyrotoxicosis

• Diffuse

• Vascular

• Large or small

• Firm or soft

• Thrill/ Bruit

Secondary Thyrotoxicosis

• Nodular

• Insidious

Gastrointestinal System

Cardiovascular System

Genitourinary system

Skeletal system

Neuromuscular System

Integument

Psychiatry

Sympathetic Overactivity

Signs

Eye Signs

• Lid Retraction

• Von Graefe’s sign (Lid Lag)

• Stellwag’s sign

Exopthalmos

• Corneal ulceration

Malignant Exophthalmos

Grading Of Exophthalmos

• MildWidening of Palpebral fissure due to lid retraction

• Moderate Orbital deposition of fat causing bulging with positive Joffroy’s sign

• Severe Congestion with intraorbital oedema, raised intraocular pressure,diplopia and ophthalmoplegia

• Progressive Inspite of proper treatment progression of eye signs is seen with chemosis, corneal ulceration and ophthalmoplegia.

Pulse Rate

• Tachycardia (Crile’s grading)

• Sleeping PR – Three consecutive nights-Average.

• Grading of PR

– Grade I <90/min

– Grade II 90-110/min

– Grade III >110/min

Other CVS manifestaions

• Atrial Fibrillation

• Atrial flutter

• Extrasystole tachycardia

• Wide pulse pressure

Myopathy

• Weakness of proximal muscles (Thigh and arm muscles)Basedow Myopathy

• Weakness more during isometric contraction(getting down steps, lifting a bucket)

• Severe( resembles Myaesthenia gravis)

Pretibial Myxoedema

• Primary Thyrotoxicosis• Bilateral, symmetrical,shiny, red thickened dry skin with

coarse hair in the feet and ankles.• Severe skin of leg also get involved.• Due to deposition of Myxomatous tissue in skin and

subcutaneous plane.• Associated with exophthalmos with high levels of thyroid

stimulating antibodies.• Skin cyanotic on cold exposure.• Thyroid dermopathy

– Pretibial myxoedema, pruritus, palmar erythema, Hair thinning, Dupytren’s contracture.

Thyroid acropachy

• Clubbing of fingers and toes

• Primary thyrotoxicosis

• Hypertrophic pulmonary Osteoarthropathy.

Others

• Thrill in the upper pole of thyroid and Bruit on auscultation.

• Hepatosplenomegaly

INVESTIGATIONS

P

H

T

TRH

TSH

T3 AND T4

----

*TSH- Thyroid stimulating hormone ( 0-5IU/ml).

*T3 f- (3-9nmol/l).

*T4 f-(8-26nmol/l).

*RA I 123.

*TRH stimulation test- obsolete nowadays.

*Serum cholesterol.

*BMR- basal metabolic rate.

*Thyroid auto antibodies.

*Werner’s T3 suppression test .

*Thyroglobulin estimation study.( 0.5-50micg/l)

* FNAC of thyroid.

PRIMARY HYPERTHYROIDISM-INTRINSIC

• Etiology-

• Grave’s disease(most common)

• Intake of iodine supplements

• Inflammation (viral, certain medications and pregnancy)

• Carcinoma of the thyroid

• Toxic adenoma.

• TSH-

• HIGH RADIO ACTIVE IODINE UPTAKE.

• T4 TEST-

• USG SCAN

• Thyroid antibodies test- Thyroid peroxidaseantibody.

-Thyroglobulinantibody.

RA Iodine123

• Cold nodule or hot nodule.

• Done in MNG

• Solitary thyroid nodule

• Retrosternal goiter

• Graves disease

• struma ovary

Follicular carcinoma to rule out secondaries

• Contra indication- Pregnancy and lactation.

SECONDARY HYPERTHYROIDISM-EXTRINSIC

• Etiology-

• Thyroid stimulating hormone secreting pituitary adenoma

• Gestational thyrotoxicosis

• HCG producing tumor.

• TSH-

• T3 AND T4-

• TRH-

• USG of the thyroid

• CT scan of the head or MRI of brain to detect tumors in the pituitary gland.

T3 TOXICOSIS

• It is observed in some cases of toxic nodular goiter and most importantly with a solitary hyperfunctioning nodule.

• This should be suspected T4 I normal and absence of thyroxine binding globulin.

• Do a t3 suppression test.

• Serum cholesterol increased in hypothyroidism

• BMR increased in hyperthyroidism

• Thyroid antibodies- primary thyrotoxicosis

• Thyroglobulin estimation- used during follow up period especially in follicular carcinoma.

• Post thyroidectomy its level decreases.

• Follow up marker in well differentiated thyroid carcinoma.

• Sudden raise occurs in thyroiditis , primary or secondary toxic goiter.

FNAC

• To investigate the pathology.

• Used in the diagnosis of papillary ,medullary , anaplastic carcinomas, cold nodules , thyroiditis.

• 23G needle is used . Minimum 6 aspiration is done.

• Done in suspicious solitary/multiple nodule /dominant nodules.

• Mostly done under ultra sound guidance.

USG

• Identifies nodules, number , size ,vascularity ,echogenicity .

• For USG guided FNAC.

• To identify neck lymph nodes

• To identify solid or cystic lesions

• Benign lesion is hyperechoic , often cystic with well differentiated margins, shows egg shell calcifications as a rim .

• Malignant lesions is hypoechoic with poor margins with high vascularity, without any perfect halo.

TRH STIMULATION TEST

• It’s a test for hypothalamic –pituitary axis .• IV TRH- 200micg- RISE in TSH in 20 minutes

and reaches to normal in 20 minutes.• In pituitary insufficiency – TH deficiency – SUB

NORMAL responseIn hypothyroidism –

elevated TSH.

• This test is useful in doubtful hyperthyroidism,hypothyroidism,t3 toxicosisand in ophthalmic graves disease.

Thyrotoxicosis Management

Medical

Radioactive Iodine

Surgical

Anti-Thyroid Drugs

Carbimazole

Propylthiouracil

Propranolol

Nadalol

Indications:

• Toxicity in pregnant women

• Toxicity in children and young

adults

• Before thyroidectomy

• Soon after starting radioactive I therapy 131

Action:

Carbimazole- acts by blocking thyroid hormone

synthesis and suppresses autoimmune process in

thyroid in grave’s disease.

Propylthiouracil- blocks thyroid hormone synthesis and

blocks peripheral conversion of T4 to T3.

Dose:

Carbimazole- 10mg x 3 or 4 times/ day,

latent interval- 7 to 14 days and maintenance

dose- 5mg x 2 or 3 times/day for 6-24 months

Propylthiouracil- 200mg 8th hourly

Alternative:

Initial high dose of Carbimazole followed by

maintenance dose of 0.1-0.15mg thyroxine daily

Side effects:

Fever

Rash

Neuritis

Agranulocytosis

Lymph node

enlargement

Arthralgia

Myalgia

Psychosis

Liver cell

dysfunction

Hepatotoxicity

Propranolol:

dose:40mg tid

Action:

reduces cardiac problems

blocks peripheral conversion of T4 to T3

Contraindications:

bronchial asthma

heart block

cardiac failure

Advantages:

No surgery

No use of radioactive substances

Disadvantages:

Prolonged treatment

Failure rate-50%

ContraindicatedLarge gland size

Severity of disease

TSH-RAb levels

Surgery

Total Thyroidectomy

Hemi Thyroidectomy

Subtotal Thyroidectomy

Indications:

• Failure of drug treatment

• Autonomous toxic nodule

• Nodular toxic goitre

• Malignancy can’t be ruled out

• Graves in children, or with nodules

• Need for antithyroid drugs >2 years

• Large goitre, substernal/ intrathoracic goitre

• Pressure symptoms, Graves ophthalmopathy

• Amiodarone-induced thyrotoxicosis

Lugol’s iodine:

decreases vascularity of the gland & makes

more firm and easier to handle during surgery

Dose: 10-30drops/day for 10 days

prevents the release of hormone from the gland-

Thyroid Constipation

After 2 weeks effect - lost causing thyroid escape

from iodine control

Advantages:

o Rapid and high cure rate

o Radioiodine therapy avoided

o Tissue for biopsy, removes occult malignant foci

o Best option for ophthalmopathy

o Women planning for a child

o Coexisting parathyroid carcinoma- removed

o For intrathoracic retrosternal toxic thyroid

Disadvantages:

Recurrent thyrotoxicosis

Thyroid insufficiency

Complications of surgery itself

Hypothyroidism

RADIOACTIVE IODINE

Destroys thyroid cells and reduces the

mass of functioning thyroid tissue to below

a critical level

I - radioactive therapy I - diagnostic

studies

131

123

Therapeutic purposes:

I 300-600MBq orally

Maintenance dose of L-thyroxine 0.1mg daily

Diagnostic purposes:

I given on empty stomach orally on previous day of diagnosis

Dose: 5 micro curie

131

123

Indications:

Primary thyrotoxicosis

Autonomous toxic nodule

Follicular carcinoma of thyroid

Ectopic thyroid

Retrosternal thyroid

Contraindications:

Pregnancy and lactation

Children

Females desiring to have

pregnancy within a year

Advantages:

No surgery

No prolonged medical therapy

Disadvantages:

Hypothyroidism

Ophthalmopathy and Dermopathy - worsened

Effects will be seen only after 3 months

Induce hyperparathyroidism

Special conditions:

Pregnancy:

Radioiodine - absolutely contraindicated

Surgery – miscarriage

Antithyroid – thyroid insufficiency

Children:

Radioiodine contraindicated

Surgery- increased risk of recurrence

because thyroid cells highly active after

thyroidectomy in young.

Thyrocardiac:

-seen in patient with severe cardiac

damage due wholly or partly to

hyperthyroidism

-middle aged or elderly

-secondary thyrotoxicosis

-hyperthyroidism not very severe

Treatment: Beta blockers, radioiodine with

antithyroid drugs

Proptosis of recent onset:

Termination of thyrotoxicosis by

thyroidectomy or radioiodine when

proptosis is recent onset – result in

malignant exophthalmos.

High titres of thyroid antibodies:

Indicates lymphatic infiltration of goitre i.e.

diffuse or focal thyroiditis.

Treatment: anti-thyroid drugs

If medical treatment fails surgery or radio-

iodine is contraindicated.

steroids - reduce pain and swelling

RECENT ADVANCES IN THYROTOXICOSIS

overview

Advances in diagnosis

Advances in surgery

- MITS

- MIVAT

- ROBOTIC

Summary

Diagnostic advances

Radioactive iodine and Tecnitium99 scan

Radioactive iodine(I123) Tecnitium99 (Tc99)

costly Cheap

Oral intake on empty stomach

IV injection

Half life is 13 hours Half life is 6 hours

Radioactive iodine scan

Tc99

Normal

Grave’s

MNG

Txadenoma

Thyroiditis

SURGICAL ADVANCES

Long neck scar makes patients uncomfortable in public/ cosmetic

Scar length reduced but still, cosmetically not acceptable

Minimally Invasive Thyroid Surgery (MITS)

First endoscopic thyroidectomy was done by HUSHER ET AL in 1997.Hüscher CS, Chiodini S, Napolitano C et al (1997) Endoscopic right thyroid lobectomy. Surg Endosc11(8):877

KANG ET AL started using Axillaryapproach for thyroidectomy

Kang J, Ikeda Y, Takami H, Sasaki Y et al (2000) Endoscopic neck surgery by the axillary approach. J Am Coll Surg 191(3):336–340

MICCOLI ET AL introduced MINIMALLY INVASIVE VIDEO ASSISTED THYROIDECTOMY (MIVAT)

Miccoli P, Berti P, Frustaci GL et al (2006) Video-assisted thyroidectomy: indications and results. Langenbecks Arch Surg 391(2):68–71

LOMBARDIE ET AL evaluated patients undergone (retrospective study of 1350 patients) MIVAT and CT and reported MIVAT had superiority over CT

Lombardi CP, Raffaelli M, Princi P et al (2005) Safety of video-assisted thyroidectomy versus conventional surgery. Head Neck 27(1):58–64

Axillary approach

Advantages:

• Reduced tissue trauma

• Short hospital stay

• Better cosmetic results

• Minimal postop pain

• Patient more comfortable

Disadvantages:

• Longer duration of surgery

• Costly

• Steep learning curve

• More than 1 surgeon required

Patient selection for MITS

INDICATIONS CONTRAINDICATIONS

Thyroid nodule size <35mm (benign) and <20mm (malignant)

Malignancy other than low risk Papillary carcinoma thyroid

Thyroid gland volume <30ml on USG Gland volume >30ml

No previous neck surgeries Associated enlarged lymph nodes

No H/o irradiation Extra thyroidal extension, substernalextension

No H/o thyroiditis Obese patient

TECHNIQUE ADV DISADV

MIVAT Small incisionReduced painShort postop

Less tissue traumaNo drains required

Only for small thyroid<30cc

Long duration of surgerySteep learning curve

MIT Small incisionBetter cosmetic scar

Long duration of surgery

What more to come in

future????

Thyroid surgery through transoral route

Robotic thyroid surgery

Robotic thyroid surgery

• da Vinci system

• Computer motion system

• Zeus robotic system

Advantage Disadvantage

Spectacular view of surgical viewStable and accurate movement

Still evolving

Facilitates multiplanar dissection Cost of instillation of the system and maintanence

Proper exposure of primary site without constant retraction for

better visualisation

Lack of training of young surgeons

Better tissue dissection as the tip if the endoscope is in close vicinity to

the tissue

Summary

Use of radioactive iodine/Tc99 for diagnosis alongwith conventional diagnostic techniques

Use of new surgical technique like MIT/MIVAT over conventional thyroidectomy

Use of robotic surgery

Future holds more!!!!

Thank you

SURJEET ACHARYA