Pathophysiology of thyroid

1. Dr Parag Yadav

3. Hypothyroidism
 Presentation from asymptomatic disease to myxoedema coma.

4. Aetiology
 Primary-
Inadequate thyroid hormone from thyroid gland
 Secondary/ central-
Pathology related to pituitary or hypothalamus

5. Primary hypothyroidism-Aetiology
 Iodine deficiency
 Autoimmune thyroid diseases
 Hashimoto thyroiditis
 Drugs- Amiodarone, Tyrosine Kinase Inhibitors(TKI), Riphampin ,
Ethionamide, Phenytoin, Carbamazepine etc.
 Thyroid Radioactive Iodine Therapy
 Thyroid Surgery
 Radiotherapy to head or neck area

6. Central hypothyroidism-Aetiology
 Neoplastic, Infiltrative, Inflammatory, Genetic, Iatrogenic disorders.
 Pituitary tumours
 Tumours compressing hypothalamus
 Sheehan syndrome
 TRH resistance
 Lymphocytic hypophysitis
 Radiation therapy to the brain
 Drugs such as dopamine, prednisone, Opioids etc.

7.  Post partum thyroiditis
 Radioactive iodine in treatment of graves disease
 Sub acute granulomatous thyroiditis

8. Epidemiology
 Prevalence among adults
 More prevalence in women with small stature at birth,
Low BMI in childhood
 Female gender and increasing age associated with higher TSH and
prevalence of Antithyroid antibodies

9. Pathophysiology

10. Histopathology
 Autoimmune thyroiditis–
Increase in turnover of iodine and impaired organification
 Chronic inflammation T cell lymphocytic infiltration lymphocytic
hyperplasia dense fibrosis an atrophic follicles

11. History
 Typical-Cold intolerance, Puffiness, Decreased sweating
 Dry skin, voice change hair loss,
constipation, fatigue muscle cramps,
cold intolerance, sleep disturbance M.C. Abnormalities,
weight gain, Galactorhoea
 Depression, anxiety, psychosis, memory loss
 Rarely- Ascites, Pericardial Effusion.

12.  Carpel tunnel syndrome, Sleep apnoea,
 Hyponatremia, Hypercholesterolemia,
 Congestive Heart Failure, Prolonged QT interval
 Hashimoto disease-
Fullness of throat, fatigue, painless thyroid enlargement

13. Evaluation
 Overt hypothyroidism
TSH elevated, free T4 low
 Subclinical hypothyroidism
TSH elevated, free T4 normal
 Central hypothyroidism-
Biologically inactive TSH.
Diagnosis on free T4

14.  Autoimmune Hypo thyroiditis
 Anti thyroid antibodies- TPO antibodies
 Euthyroid sickness-
 In hospitalized patients.
 Reverse T3 elevated
 Hyperlipidaemia, elevated serum CK, elevated hepatic enzymes, anaemia,
increased BUN, creatinine, uric acid

15. Lab investigations

16. Treatment
 Levothyroxine monotherapy
 1.6 mcg/kg/day
 30-45 min before breakfast or at least 3 hrs post meal
 Proton pump inhibitors negative impact on levothyroxine absorption

17.  IV form of drug in myxedema coma
 Gel formulations- triocent- in malabsorptionsyndrome
 Sucralfate, calcium preparation, bile acid sequestrants- interfere
absorption
 Lab- every 4-8 weeks until target achieved. 6 months after stable

18.  Cardiac disease-
Monitor for angina/ A.F. Over treated for extended period of time
Osteoporosis

19. Prognosis
Failure to treat - Severe mental retardation in children
In adult- Heart failure

20. Complications
 Myxoedema coma
 Myxedema crisis-
Encephalopathy, hypothermia, seizures, hyponatremia, hypoglycaemia,
Arythmia, respiratory failure.
 Treatment-
Thyroid replacement treatment with IV hydrocortisone

21. Hyperthyroidism
 Hypothyroidism is a Syndrome associated with
excess thyroid hormone production
 Thyrotoxicosis is a state of excess thyroid hormone
exposure to tissues

22.  Overt hyperthyroidism
low TSH, elevated T3, T4
 T3 toxicosis
T3 elevated, normal T4, low TSH
 Subclinical hyperthyroidism
low TSH, normal T3 And T4

23. Etiology
 Graves disease
 Toxic Multinodular Goiter
 Toxic adenoma
 Other-
 Iodine induced
 TSH secreting pituitary adenoma
 Coditions with high HCG levels
 Ectopic thyroid in struma ovarii
 Extensive metastasis from thyroid Ca
 Drug induced Thyroiditis
 Factitious thyroiditis (excessive use of pharmaceutical thyroid hormone)

25. Pathophysiology
 Graves disease-
Autoimmune process.
Antibodies against TSH receptors  increase production and release of
thyroid hormone
 Toxic multi nodular goiter
Development of nodular disease  somatic mutation lead to activation of
cAMP pathway  Hyperthyroidism

26.  Iodine induced hyperthyroidism -
From excessive iodine intake
Excess iodide inhibit organification (iodide to thyroid conversion). This is
Wolff-chaikoff effect.
Fails in “Jod-basedow phenomenon” Excess thyroid hormone
 Amiodarone induced thyrotoxicosis
1. With pre existing thyroid diseases
2. Destructive thyroiditis due to toxic effect of amiodarone

27. Thyroiditis
 Inflammation and destruction of thyroid follicle cells
 1. Autoimmune cause
 2. external factors-infection, drug induced

28. History
 Hyperadrenergic and hypermetabolic state like symptoms
 Palpitation tremors
 Heat intolerance dyspnea on exertion
 Anxiety irritability
 Fatigue hair loss
 Oligomenorhoea/amenorhoea
 Subactue thyroiditis-
Anterior neck pain and fever
 Eye signs-Lid lag, Lid retraction
Diplopia, excessive tearing

29. EVALUATION
 Measurement of TSH, Free T4 & Total T3
 Overt hyperthyroidism -
low TSH, elevated T3, T4
 T3 toxicosis -
T3 elevated, normal T4, low TSH
 Subclinical hyperthyroidism -
low TSH, normal T3 And T4
 Heterothile antibodies – false elevation of TSH
 Biotin – high dose biotin- falsely low TSH

30.  Measurement of thyrotropin receptor antibody(TRAb) – elevated in
“Graves Disease”
 If TRAb is normal – Radio-iodine thyroid uptake
High Uptake –
1. Graves Disease – Diffuse pattern
2. TMNG – Patch pattern
3.Thyroid Adenoma- solitary area high uptake
Low uptake
1.Thyroidities
2.Iatrogenic

31. Lab investigations