2. The Endocrine system for dental students DR IBRAHIM HASSAN ALZAHRANI FRCPath -UK Chairman of Pathology Departement Faculty of Medicine

3. CONTENTS: Pituitary gland –Hypopituitarism –Hyperpituitarism –Posteroir pituitary syndromes Thyroid galnd –Hypothyrodism –Hyperthyrodism –Goiter –Thyrodidtis –Tumors Parathyroid glands –Hyperparathyroidism –Hypoparathyroidism

4. Adrenal gland –Cortex –Medulla. Tumors Multiple endocrine neoplasia Endocrine pancreas (D.M )

5. THYROID GLAND

6. This is the normal appearance of the thyroid gland on the anterior trachea of the neck..

8. Normal thyroid seen microscopically consists of follicles lined by a cuboidal epithelium and filled with pink, homogenous colloid

9. Hypothyroidism: Causes: –s–structural or functional –9–95% are due to: Surgical or radiation ablation Hashimoto’s thyroiditis Primary idiopathic hypothyroidism

10. Cretinism This is uncommon disease of childhood due to failure of thyroid to synthesize thyroid hormones  hypothyroidism

11. Myxedma, cretenism

12. Neurologic & myxedematous patterns Clinically: –mental retardation –growth retardation (short stature) –coarse facial features with dry skin and protruding tongue –muscle weakness and umbilical hernia

13. Myxedema Hypothyroidism in adult. - Clinically: –appear insidiously & subtle –lethargy & weakness with slow speech –cold intolerance with cool & rough skin –menstrual problems & psychosis –cardiac changes:  cardiac output, hypertrophy, (myxedema heart), pericardial effusion –deposition of mucopolysaccharides in connective tissue –atherosclerosis ( cholesterol)

14. Hyperthyroidism Excess thyroid hormone (Thyrotoxicosis) Causes: –primary diffuse toxic hyperplasia (Grave’s disease) > 95% –toxic multinodular goiter –toxic adenoma –certain form of thyroiditis –secondary to pituitary or hypothalamic lesion

15. Clinical features: nervousness and emotional instability menstrual changes fine tremors of the hands heat intolerance with warm skin and sweating weight loss despite a good appetite

16. Eye changes: (exopthalmos, widened palpebral fissures, staring gaze) Cardiac changes: (tachycardia, palpitations, atrial fibrillation and thyrotoxic cardiomyopathy-----  cardiac failure) skeletal muscle atrophy and fatty infiltration lymphadenopathy fatty change of the liver Osteoporosis

17. Thyrotoxicosis Upper, thyrotoxicosis Lower, after treatment

18. Goiter Goiter simply means enlarged thyroid

20. Diffuse Goiter Characterized by diffuse symmetrical enlargement of thyroid (200 - 300 gm) with normal thyroid function. Hypofunction may occur early in the course. Usually occurs in: Endemic areas ( iodine & goiterogens) or Sporadic (physiological,autoimmune, familial ).

21. Multinodular Goiter Characterized by nodular asymmetrical enlargement of thyroid (up to 1000 gm) Slowly evolves from diffuse goiter.It can be toxic or non-toxic

22. Solitary thyroid nodule Size  (symptoms) Possible hyperfunction Usually colloid nodule >70% Adenoma 20-30% Carcinoma <5%  - Radioactive iodine (Hot & cold nodule) FNA & biopsy Thyroid function

23. Solitary thyroid nodule Invisigations : thyroid hormons: (T3,T4,TSH) radiological examinations : * ultrasound (cystic/solid) * radioactive iodine (cold/hot) Fine needle aspiration cytology

24. GRAVE’S DISEASE Primary Diffuse Toxic Hyperplasia The most common cause of thyrotoxicosis It is an autoimmune disease Classically shows: –1-Exopthalmos (proptosis) –2-Dermopathy (pretibial myxedema) –3-Hyperthyroidism Common in ♀ 3rd & 4th decade ♀ : ♂ = 10 : 1 HLA – DR3 & Familial predisposition Other autoimmune diseases may occur

25. Pathogenesis B-cells secrete autoantibodies against mainly TSH – Receptors (Abs. against microsomes, thyroglobulin, T3 & T4 can be seen)

26. Morphology Gross: diffuse symmetrical enlargement of thyroid

27. THYROIDITIS Hashimoto’s thyroiditis Subacute (granulomatous,DeQuervian) thyroiditis Chronic lymphocytic (painless) thyroiditis Riedel’s fibrous thyroiditis

28. Hashimoto’s thyroiditis This is an autoimmune most common type of thyroiditis characterized by symmetrical modesty enlarged thyroid responsible for most cases of primary goiterous hypothyroidism.

29. Pathogenesis B cells  autoantibodies against microsomes and thyroglobulin. Cell-mediated destruction of the gland ♀ : ♂ = 10 : 1 middle-aged Higher incidence of autoimmune disease

30. Clinical Course Euthyroid---  hypothyroid Moderate goiter Hashitoxicosis(hyperthyroidism) occasionally 5% - B cell lymphoma or rarely papillary carcinoma of thyroid

31. THYROID TUMOURS 1-BENIGN: Follicular adenoma 2-MALIGNANT: Carcinoma of thyroid –Papillary carcinoma –Follicular carcinoma –Medullary carcinoma –Anablastic carcinoma –Lymphoma Others – rare (sq. ca, sarcomas, metastasis)

32. ADENOMA Always follicular adenoma No papillary adenoma of thyroid. Solitary & encapsulated. No capsular invasion. Histology: Follicles –> macro (colloid), micro (fetal), normal size (simple), trabecular (embryonal). Sometimes composed of Hürthl cells (oncocytic)  Hurthle cell adenoma.

33. ADENOMA

34. ADENOMA

35. CARCINOMA OF THYROID Causes: –Ionizing radiation –Hashimoto’s thyroiditis –Grave’s disease?

36. Papillary Carcinoma 60-70% The most common type Young age 20-50y, F:M=3:1 Forming papillae and psammoma bodies Cells typically show ground-glass appearance with clear grooved nuclei “Orphan Annie” and intranuclear inclusion 50% at presentation  Cervical LN metastasis Haematogenous spread is rare (not common)

37. Follicular variant of papillary carcinoma : No papillary formation. The nuclei shows typical nuclear ground glass appearance of papilary crcinoma. Grow slowly with indolent course Occult microscopic variant

38. Papillary Carcinoma

39. Follicular Carcinoma Macroscopically often encapsulated similar to adenoma Histologically : composed of follicles with no papillary formation and no groundglass nuclear changes. sometimes the cells are oncocytic  (Hurthle cell carcinoma).

40. Follicular Carcinoma Haematogenous spread (lung, bone, liver.. ) Poorer in prognosis than papillary carcinoma. Represent approximatly 15% Most patients are >40y TYPES: 1- minimally invasive FC. 2- widely invasive FC.

41. Medullary Carcinoma of thyroid <5% Derived from calcitonin – secreting C-cells Characterized by formation of amyloid material from calcitonin, surrounded by small to medium sized cells with round to spindle shaped nuclei forming sheets, nests or cords

42. Medullary Carcinoma amyloid

43. Medullary Carcinoma It has slow but progressive growth Both lymphatic and hematogenous metastasis occurs 10-20% are familial, multicenteric in young age, associated with MEN 2&3 Immuno: +ve calcitonin 80-90% sporadic, solitary, old age

44. Anablastic carcinoma 5-10% 0ccurs in patient > 60 y Poorly differentiated, highly malignant tumour usually forms bulky necrotic mass often disseminate extensively through blood death occurs within 1-2 years (<10% survive for 10y) Histological variants: Giant cells, spindle cells(sarcomatoid), squamoid cells

47. PARATHYROID GLAND

49. Hyperparathyroidism - Primary Hyperparathyroidism: Increase PTH due to parathyroid lesion (Adenoma/hyperplasia)  Hypercalcaemia PTH  Hypercalcaemia : – osteoclast to mobilize Ca++ from bone – Ca++ reabsorption in the kidney – Ca++ absorption in Git.through vit.D. – excretion of phosphate in urine. Part of MEN I & II F : M = 3 : 1 > 40y

50. Clinical features Asymptomatic (lethargy&weakness) Bone pain (osteomalacia, osteoporosis & osteitis fibrosa cystica/brown tumor ) Renal stones (nephrolithiasis) Nephrocalcinosis Metastatic calcification (blood vessels, soft tissue & & joints) Abdominal pain (peptic ulcer,pancreatitis) and mental change

51. Parathyroid adenoma adenoma normal

52. Adenoma & Hyperplasia In adenoma one gland, Hyperplasia >one gland Frozen section (intraoperative consultation) required to confirm presence of parathyroid tissue. Carcinoma of parathyroid : * Rare –Invasion and metastasis –Bands of collagen in the stroma –High mitotic figures.

53. Parathyroid carcinoma

54. MULTIPLE ENDOCRINE NEOPLASIA

55. MULTIPLE ENDOCRINE NEOPLASIA (MEN) MEN are syndromes characterized by hyperplasic or neoplastic involvement of at least two endocrine glands and sometimes associated with non-endocrine lesions.

56. MEN I:Wermer ’ s Syndrome – Parathyroid adenom/hyperplasia. – Pituitary adenoma. – Pancreatic lesions (hyperplasia adenoma, carcinoma ) –Mutant gene(MEN1) locus at 11q13 –Autosomal dominnant

57. MEN II (IIa):Sipple Syndrome – Medullary carcinoma of thyroid – Pheochromocytoma. – Occasionally parathyroid lesion (30%) – Mutant gene locus at 10q11.2 (RET proto-oncogen) – Autosomal dominant

58. MEN III (IIb):William syndrome: similar to MEN II plus – Marfanoid bodily habitus – Multiple mucocutanenous ganglioneuromas – Parathyroid involvement : (none/rare).