Pathology of Thyroid & Endocrine Disorders

1. Pathology of Thyroid & Endocrine Disorders Challenge….! Jan 2009: 4 th Year Students at JCU School of Medicine set new record.…!!! 100% Pass & Class Average of over 70% 99% Pass & Class Average of 68% Highest Are you ready for the Challenge….? Yes We Can…!

2. CPC06-4.3.1 <ul><li>Mina Gupta, 48 year old woman, lives in Mt Isa, presents to her GP with a swelling in her neck & fatigue. </li></ul><ul><ul><li>Duration of swelling: 2/12 </li></ul></ul><ul><ul><li>Painful, some discomfort lower neck (rate 2/10) </li></ul></ul><ul><ul><li>Site: central, mid- neck </li></ul></ul><ul><ul><li>Voice change: No </li></ul></ul><ul><ul><li>Weight loss/gain? put a bit of weight on as her clothes feel a bit tight. </li></ul></ul><ul><ul><li>Fatigue? Worsening fatigue last few months. Sleeping well but always feels tired. </li></ul></ul> CPC06-4.3.1 <ul><li>Mina Gupta, 48 year old woman, lives in Mt Isa, presents to her GP with a swelling in her neck & fatigue. </li></ul><ul><ul><li>Duration of swelling: 2/12 </li></ul></ul><ul><ul><li>Painful, some discomfort lower neck (rate 2/10) </li></ul></ul><ul><ul><li>Site: central, mid- neck </li></ul></ul><ul><ul><li>Voice change: No </li></ul></ul><ul><ul><li>Weight loss/gain? put a bit of weight on as her clothes feel a bit tight. </li></ul></ul><ul><ul><li>Fatigue? Worsening fatigue last few months. Sleeping well but always feels tired. </li></ul></ul>

3. CPC06-4.3.1 – Physical Exam <ul><li>Vitals: T 36.8C rr 12/min BP : 110/64 mmHg pulse : 64 bpm reg good volume BMI : 32 </li></ul><ul><li>Peripheries: ? pale palmar creases , cool hands mild bilateral pitting oedema nil else abnormal </li></ul><ul><li>Head + neck conjunctival pallor +; xanthelasma bilaterally; diffuse firm slightly tender central neck mass which moves on swallowing; no bruit; no periorbital oedema; no LN. </li></ul><ul><li>Pemberton’s sign negative </li></ul><ul><li>CVS + Resp: nil abnormal </li></ul><ul><li>GI + Renal: nil abnormal </li></ul><ul><li>CNS: K10 score 32 ; </li></ul><ul><li>depressed ankle reflexes bilaterally (delayed return) </li></ul>? ? ? CPC06-4.3.1 – Physical Exam <ul><li>Vitals: T 36.8C rr 12/min BP : 110/64 mmHg pulse : 64 bpm reg good volume BMI : 32 </li></ul><ul><li>Peripheries: ? pale palmar creases , cool hands mild bilateral pitting oedema nil else abnormal </li></ul><ul><li>Head + neck conjunctival pallor +; xanthelasma bilaterally; diffuse firm slightly tender central neck mass which moves on swallowing; no bruit; no periorbital oedema; no LN. </li></ul><ul><li>Pemberton’s sign negative </li></ul><ul><li>CVS + Resp: nil abnormal </li></ul><ul><li>GI + Renal: nil abnormal </li></ul><ul><li>CNS: K10 score 32 ; </li></ul><ul><li>depressed ankle reflexes bilaterally (delayed return) </li></ul>? ? ?

4. CPC06-4.3.1- Differential <ul><ul><li>Thyroid: </li></ul></ul><ul><ul><ul><li>Goitre – what ? type? </li></ul></ul></ul><ul><ul><ul><li>Hyper/Hypo/Euthyroid? </li></ul></ul></ul><ul><ul><ul><li>Thyroid nodule - cyst, adenoma, Cancer </li></ul></ul></ul><ul><ul><ul><li>Autoimmune thyroiditis – Graves? Hashimoto? </li></ul></ul></ul><ul><ul><ul><li>Thyroid cancer - ? Papillary ? Follicular ? Other </li></ul></ul></ul><ul><ul><li>What other differentials? </li></ul></ul><ul><ul><ul><li>Lymphadenitis, salivary gland tumors, Lymphoma, thymoma, secondary deposits. </li></ul></ul></ul><ul><ul><ul><li>Psychological, Diet, DM, Hypertension, Obesity. </li></ul></ul></ul> CPC06-4.3.1- Differential <ul><ul><li>Thyroid: </li></ul></ul><ul><ul><ul><li>Goitre – what ? type? </li></ul></ul></ul><ul><ul><ul><li>Hyper/Hypo/Euthyroid? </li></ul></ul></ul><ul><ul><ul><li>Thyroid nodule - cyst, adenoma, Cancer </li></ul></ul></ul><ul><ul><ul><li>Autoimmune thyroiditis – Graves? Hashimoto? </li></ul></ul></ul><ul><ul><ul><li>Thyroid cancer - ? Papillary ? Follicular ? Other </li></ul></ul></ul><ul><ul><li>What other differentials? </li></ul></ul><ul><ul><ul><li>Lymphadenitis, salivary gland tumors, Lymphoma, thymoma, secondary deposits. </li></ul></ul></ul><ul><ul><ul><li>Psychological, Diet, DM, Hypertension, Obesity. </li></ul></ul></ul>

5. Oprah has battled with her weight for years. Recently  she was diagnosed with hyperthyroidism . which sped up her metabolism and prevented sleep. Oprah eventually &quot;blew out&quot; her thyroid and experienced classic symptoms of hypothyroidism : Her metabolism slowed and she felt sluggish and tired. Hyper - - Hypo Oprah has battled with her weight for years. Recently  she was diagnosed with hyperthyroidism . which sped up her metabolism and prevented sleep. Oprah eventually &quot;blew out&quot; her thyroid and experienced classic symptoms of hypothyroidism : Her metabolism slowed and she felt sluggish and tired. Hyper - - Hypo

6. Sir William Osler, M.D. said… As is our pathology so is our practice... what the pathologist thinks today, the physician does tomorrow. Pathology, The science of Medicine Sir William Osler, M.D. said… As is our pathology so is our practice... what the pathologist thinks today, the physician does tomorrow. Pathology, The science of Medicine

7. Pathology Core Learning Issues: <ul><li>Pathology Major CLI: </li></ul><ul><ul><li>Overview of Endocrine disorders (classification, etiology, Pathogenesis, clinical & laboratory diagnosis). </li></ul></ul><ul><ul><li>Thyroid Disorders – Hyper, Hypo thyroidism Pathophysiology & clinical features. </li></ul></ul><ul><ul><li>Pathology of Graves & Hashimoto thyroiditis. </li></ul></ul><ul><ul><li>Tumours of thyroid – Goitre - Multinodular, Adenoma & Carcinoma (Papillary, follicular) </li></ul></ul><ul><ul><li>Laboratory diagnosis of thyroid disorders. </li></ul></ul><ul><li>Pathology Minor CLI: </li></ul><ul><ul><li>Other common Endocrine disorders – Cushings sy. & disease, addisons, Sheehan’s, Adrenogenital syndrome, Pituitary adenoma, Gigantism & Acromegaly, Diabetes insipidus.MEN syndromes. </li></ul></ul> Pathology Core Learning Issues: <ul><li>Pathology Major CLI: </li></ul><ul><ul><li>Overview of Endocrine disorders (classification, etiology, Pathogenesis, clinical & laboratory diagnosis). </li></ul></ul><ul><ul><li>Thyroid Disorders – Hyper, Hypo thyroidism Pathophysiology & clinical features. </li></ul></ul><ul><ul><li>Pathology of Graves & Hashimoto thyroiditis. </li></ul></ul><ul><ul><li>Tumours of thyroid – Goitre - Multinodular, Adenoma & Carcinoma (Papillary, follicular) </li></ul></ul><ul><ul><li>Laboratory diagnosis of thyroid disorders. </li></ul></ul><ul><li>Pathology Minor CLI: </li></ul><ul><ul><li>Other common Endocrine disorders – Cushings sy. & disease, addisons, Sheehan’s, Adrenogenital syndrome, Pituitary adenoma, Gigantism & Acromegaly, Diabetes insipidus.MEN syndromes. </li></ul></ul>

8. Pathology Lab resources: Muse um Specimens GN-01 Pheochromocytoma GN-02 Adenoma (Hurthle Cell) GR-01 Adrenal Haemorrhage GR-02 Nodular Thyroid GR-03 Nodular Hyperplasia (MNG) GR-04 Benign Nodular Thyroid (MNG) GR-05 Thyroid Cyst Digital Slides Thyroid Graves (JCU slide) Endo-39-Thyroid MNG Endo-40-Adrenal adenoma Endo-46-Pheochromocytoma Endo-47-Hashimoto-Pap ca Endo-51-Hashimotos thyroiditis Endo-52-Hashimotos thyroiditis Endo-53-Graves Endo-54-Hashimotos thyroiditis Endo-57-Pitutary Normal Endo-58-Thyroid Normal Endo-59-Adrenal Normal Pathology Lab resources: Muse um Specimens GN-01 Pheochromocytoma GN-02 Adenoma (Hurthle Cell) GR-01 Adrenal Haemorrhage GR-02 Nodular Thyroid GR-03 Nodular Hyperplasia (MNG) GR-04 Benign Nodular Thyroid (MNG) GR-05 Thyroid Cyst Digital Slides Thyroid Graves (JCU slide) Endo-39-Thyroid MNG Endo-40-Adrenal adenoma Endo-46-Pheochromocytoma Endo-47-Hashimoto-Pap ca Endo-51-Hashimotos thyroiditis Endo-52-Hashimotos thyroiditis Endo-53-Graves Endo-54-Hashimotos thyroiditis Endo-57-Pitutary Normal Endo-58-Thyroid Normal Endo-59-Adrenal Normal

9. Endocrine Glands: Overview <ul><li>Classification: Exocrine (ducts), Endocrine (ductless) </li></ul><ul><li>Site of Action: Autocrine, Paracrine & Endocrine </li></ul><ul><li>Type of secretion: Merocrine, Apocrine, Holocrine. </li></ul><ul><li>Endocrine System: </li></ul><ul><ul><li>Hypothalamus  Pituitary  End. Glands  Tissues. </li></ul></ul><ul><li>Endocrine disorders: </li></ul><ul><ul><li>Primary(gland), Sec..(pituitary), Tertirary (Hypothal) </li></ul></ul><ul><ul><li>Hyperfunction / Hypofunction / Eufunction </li></ul></ul><ul><ul><li>Common Tumors – adenoma/carcinoma </li></ul></ul><ul><li>Etiology: Genetic / Familial / Acquired </li></ul><ul><li>Multiple Endocrine Neoplasia (MEN) Syndromes. </li></ul> Endocrine Glands: Overview <ul><li>Classification: Exocrine (ducts), Endocrine (ductless) </li></ul><ul><li>Site of Action: Autocrine, Paracrine & Endocrine </li></ul><ul><li>Type of secretion: Merocrine, Apocrine, Holocrine. </li></ul><ul><li>Endocrine System: </li></ul><ul><ul><li>Hypothalamus  Pituitary  End. Glands  Tissues. </li></ul></ul><ul><li>Endocrine disorders: </li></ul><ul><ul><li>Primary(gland), Sec..(pituitary), Tertirary (Hypothal) </li></ul></ul><ul><ul><li>Hyperfunction / Hypofunction / Eufunction </li></ul></ul><ul><ul><li>Common Tumors – adenoma/carcinoma </li></ul></ul><ul><li>Etiology: Genetic / Familial / Acquired </li></ul><ul><li>Multiple Endocrine Neoplasia (MEN) Syndromes. </li></ul>

10. . Major Endocrine Glands: Self Study…..!

11. . 8. A PLEASING PERSONALITY WITH PMA Assembling an attractive personality is a must. Your personality is your greatest asset or your greatest liability, for it embraces everything that you control: mind, body, soul and spirit. Learn to be pleasant even when others are being unpleasant to you. Positive Mental Attitude: 17 Success Principles… Some bring happiness where ever they go, & some whenever….!

12. . Pathology of Thyroid Disorders Dr. Venkatesh M. Shashidhar Associate Prof. & Head of Pathology

13. . <ul><li>Thyroid Anatomy: </li></ul><ul><li>Location ? </li></ul><ul><li>Arteries ? </li></ul><ul><li>Veins ? </li></ul><ul><li>Lymphatics ? </li></ul><ul><li>Nerve supply ? </li></ul>

14. . Thyroid Examination:

15. . Thyroid Introduction: <ul><li>Epithelial endocrine gland (C cells, PTH) </li></ul><ul><li>Iodinated Tyrosine  T3 & T4  stored in colloid. </li></ul><ul><li>TRH  TSH  Thyroid  T3/T4  Metabolism. </li></ul><ul><li>Thyroid disease 5% of population – Females* </li></ul><ul><li>Wide clinical presentation: </li></ul><ul><ul><li>Mood changes to cardiac failure, </li></ul></ul><ul><ul><li>growth retardation - malignancy.. ! </li></ul></ul><ul><li>Hyperthyroidism </li></ul><ul><ul><li>Graves , Subacute & Multinodular Goitre. </li></ul></ul><ul><li>Hypothyroidism </li></ul><ul><ul><li>Hashimoto’s , Atrophy, Radiotherapy. </li></ul></ul><ul><li>Normal thyroid ( Euthyroid ) – neoplasms </li></ul><ul><li>Goitre: enlargement of thyroid without functional, inflammatory or neoplastic alterations. (Latin=gutter=throat) </li></ul>

16. . Variation in histology:

17. . Thyroid Function: Testing

18. . Primary – Secondary – Tertiary Gland – Pituitary - Hypothalamus T3/T4 - TSH - TRH

19. . Primary hypoThy Seconary hypothy Neoplastic hyperthy Secondary Hyperthy Throid Func. Testing

20. . Diagnosing thyroiditis. * RAIU = radioactive iodine uptake

21. . Graves Hashimoto

22. . Thyroid - Normal

23. . Normal Thyroid & Parathyroid

24. . Normal Thyroid & Parathyroid Thyroid - Parathyroid

25. . Normal Thyroid B A C

26. . C cells of thyroid ImmunoPeroxidase stain ? Function ? Tumor

27. . Thyroid Disorders: <ul><li>Clinical Syndromes: </li></ul><ul><ul><li>Hyperthyroidism – with/without goitre. </li></ul></ul><ul><ul><li>Hypothyroidism - with/without goitre. </li></ul></ul><ul><ul><li>Euthyroid – with structural abnormality. </li></ul></ul><ul><li>Swellings: </li></ul><ul><ul><li>Goitre – diffuse, multinodular, single nodule. </li></ul></ul><ul><ul><li>Neoplasm – adenoma, carcinoma. </li></ul></ul>

28. . Congenital / other Disorders: <ul><li>Thyroglossal Cyst </li></ul><ul><li>Accessary thyroids </li></ul><ul><li>Abnormal location </li></ul><ul><li>Cong. Atrophy </li></ul><ul><li>Cong. Hypertrophy </li></ul>

29. . Hypothyroidism <ul><li>Cretinism - children </li></ul><ul><li>Myxedema - adults </li></ul><ul><li>Causes: </li></ul><ul><ul><li>Developmental – Atrophy, hypoplasia </li></ul></ul><ul><ul><li>Radiation/Surgery </li></ul></ul><ul><ul><li>Hashimoto’s thyroiditis </li></ul></ul><ul><ul><li>Iodine deficiency </li></ul></ul><ul><ul><li>Drugs – PAS, iodides, lithium </li></ul></ul><ul><ul><li>Pituitary disorders </li></ul></ul>

30. . Congenital hypothyroidism: <ul><li>Protruding tongue </li></ul><ul><li>Growth retardation </li></ul><ul><li>Jaundice </li></ul><ul><li>Dry skin </li></ul><ul><li>Slow reflexes </li></ul><ul><li>Hoarse voice </li></ul>

31. . Hypothy.. <ul><li>Hypometabolism: </li></ul><ul><li>Weight gain </li></ul><ul><li>Apathy </li></ul><ul><li>Constipation </li></ul><ul><li>Menorrhagia </li></ul><ul><li>Muscle weakness </li></ul>

32. . Hypothyroidism: <ul><li>Dull and apathetic face </li></ul><ul><li>Periorbital puffiness </li></ul><ul><li>Loss of lateral eyebrows. </li></ul><ul><li>Skin Yellow (carotene, not Jaundice) cold, dry, rough, nonpitting edema (myxedema). </li></ul><ul><li>Droopy eyes. Eye lid edema. </li></ul><ul><li>Coarse, dry & thin Hair. </li></ul><ul><li>Hoarseness of voice. </li></ul>You should be able to identify hypothyroid patients at first look..!

33. . Hypothyroidism: Pale gland.

34. . Hyperthyroidism <ul><li>Thyrotoxicosis </li></ul><ul><li>Causes </li></ul><ul><ul><li>Graves – autoimmune, toxic </li></ul></ul><ul><ul><li>Toxic multinodular goitre </li></ul></ul><ul><ul><li>Functioning adenoma </li></ul></ul><ul><li>Solid, grey hyperemic gland. </li></ul><ul><li>Microscopy: Epithelial hyperplasia, hypertrophy, scanty colloid (Scalloping). </li></ul><ul><li>Lymphocyte infiltration. </li></ul>

35. . Hyper-Thy: <ul><li>Hypermetabolism: </li></ul><ul><li>Weight loss </li></ul><ul><li>Anxiety </li></ul><ul><li>Diarrhoea </li></ul><ul><li>Menorrhagia </li></ul><ul><li>Osteoporosis </li></ul><ul><li>Proximal myopathy </li></ul><ul><li>Pretibial myxoedema </li></ul><ul><li>Exophthalmos </li></ul><ul><li>Lid lag. </li></ul>

36. . Normal - Graves

37. . Clinical features: <ul><li>Weight loss </li></ul><ul><li>Anxiety, tremor </li></ul><ul><li>Diarrhoea </li></ul><ul><li>Exophthalmos * </li></ul><ul><li>Acropachy * </li></ul><ul><li>Myxedema </li></ul><ul><li>Loss of lateral eyebrow </li></ul>You should be able to identify hyperthyroid patients at first look..! Visible cornia

38. . Hyperthyroidism – exophthalmia Note:  Unilateral prominance or Severe 

39. . Thyrotoxicosis: Clin Myxedema Alopecia Acropachy Loss of lateral eyebrow Carotenemia -- normal

40. . ? Test … ? Result … ? cause Lid Lag…

41. . 3. GOING THE EXTRA MILE Very simply, this principle means: Render or give more and better service than you are paid for, and sooner or later you will receive compound interest from your investment of going the extra mile. Positive Mental Attitude: 17 Success Principles…

42. . Hashimoto Thyroiditis <ul><li>Common cause of non endemic goitre. </li></ul><ul><li>Aged females more common 45-65y. </li></ul><ul><li>Autoimmune thyroiditis HLA-DR5, DR3. </li></ul><ul><li>T cell mediated, Antithyroglobulin Ab & Antithyroid peroxidase Ab. </li></ul><ul><li>Firm, pale grey, gland enlargement - intact capsule. </li></ul><ul><li>Atrophic follicles & lymphoid follicles. </li></ul><ul><li>H ü rthle cells – eosinophilic epithelial cells. </li></ul><ul><li>Initial hyperthyroidism – hypothyroidism. </li></ul><ul><li>High risk of developing B cell lymphoma. </li></ul>

43. . Hashimoto’s Disease Atrophic Thy Fol Ly. Follicle

44. . Hashimoto’s Disease Atrophic Thy Fol Ly. Follicle

45. . Hashimoto’s – Lymphocytes & Hurthle cells. Lymphocytes Hurthle cells Ly. Follicle

46. . Antimicrosomal Ag/Peroxidase (TPO)Ab -ve Colloid +ve Cells

47. . Antithyroglobulin Antibody +ve colloid -ve cells

48. . Graves Disease: <ul><li>Common cause of hyperthyroidism (2%F) </li></ul><ul><li>Females, 20-40years, Autoimmune Thyroiditis. </li></ul><ul><li>Triad of clinical features, </li></ul><ul><ul><li>Hyperthyroidism </li></ul></ul><ul><ul><li>Infiltrative ophathalmopathy - exopthalmos </li></ul></ul><ul><ul><li>Infiltrative dermopathy – Pretibial myxedema. </li></ul></ul><ul><li>Autoantibody to TSH receptor – LATS . </li></ul><ul><li>Gross : soft, smooth, red, Hyperaemic, enlarged gland. (Bruit on auscultation) </li></ul><ul><li>Micro : Diffuse hyperplasia, ep. papillary folds, inflammation – Lymphoid Follicles (Less) Scalloped, pale, scanty colloid. </li></ul>

49. . Iodine-123 scan - Graves Cold nodule Pyramidal lobe <ul><li>Iodine-123 thyroid scan in a patient with Graves disease. The 5-hour iodine uptake was elevated at 29%. </li></ul><ul><li>Note the pyramidal lobe, which often is visualized in a hyperstimulated gland. </li></ul><ul><li>The cold nodule in the right lobe must be addressed in the same way a solitary cold nodule in a patient without Graves disease is evaluated. </li></ul>

50. . Iodine-123 scan <ul><li>Radioactive iodine uptake scan showing normal condition in a 30-year-old woman with postpartum thyroiditis (subacute lymphocytic thyroiditis). </li></ul><ul><li>Radioactive iodine uptake scan showing hyperthyroid (increased uptake) condition in a 52-year-old woman with Graves' disease </li></ul>