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Patho Endocrine


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Patho Endocrine

  3. 3. <ul><li>Bean-shaped organ </li></ul><ul><li>Measures 1 cm in greatest diameter </li></ul><ul><li>Weighs about 0.5 grams </li></ul>
  4. 7. Anterior Pituitary <ul><li>Somatotrophs </li></ul><ul><ul><li>Acidophilic cells; GH </li></ul></ul><ul><li>Lactotrophs (mammotrophs) </li></ul><ul><ul><li>Acidophilic cells; prolactin </li></ul></ul><ul><li>Corticotrophs </li></ul><ul><ul><li>Basophilic cells; ACTH, POMC, MSH, endorphins, lipotropin </li></ul></ul><ul><li>Thyrotrophs </li></ul><ul><ul><li>Basophilic cells; TSH </li></ul></ul><ul><li>Gonadotrophs </li></ul><ul><ul><li>Basophilic cells; FSH, LH </li></ul></ul>
  5. 9. Clinical Manifestations of Pituitary Disease <ul><li>Hyperpituitarism </li></ul><ul><ul><li>Arising from excess secretion of trophic hormones </li></ul></ul><ul><ul><li>Causes: pituitary adenoma, hyperplasia and carcinomas of the anterior pituitary, secretion of hormones by non-pituitary tumors, and certain hypothalamic disorders </li></ul></ul><ul><li>Hypopituitarism </li></ul><ul><ul><li>Ischemic injury, surgery or radiation, inflammatory reactions, nonfunctioning adenoma, pituitary apoplexy, Sheehan’s syndrome, Rathke cleft cyst, empty sella syndrome, genetic defects </li></ul></ul><ul><li>Local mass effects </li></ul><ul><ul><li>Earliest changes are radiographic abnormalities of the sella turcica </li></ul></ul><ul><ul><ul><li>Sellar expansion, bony erosion, and disruption of diaphragma sella </li></ul></ul></ul><ul><ul><li>Bitemporal hemianopsia; increase ICP </li></ul></ul><ul><ul><li>Pituitary apoplexy – acute hemorrhage into an adenoma with rapid enlargement of the lesion </li></ul></ul><ul><li>Disease of Posterior pituitary come to clinical attention due to increase or decrease secretion </li></ul>
  6. 10. Pituitary Adenomas and Hyperpituitarism <ul><li>Most common cause of hyperpituitarism is an adenoma arising in the anterior lobe </li></ul><ul><li>Pituitary adenomas are classified on the basis of hormone(s) produced by the neoplastic cells detected by immunohistochemical stains performed on tissue sections </li></ul><ul><li>Can secrete two hormones (GH and PRL);rarely plurihormonal </li></ul><ul><li>May be hormone-negative – may cause hypopituitarism </li></ul>
  7. 11. Pituitary Adenomas and Hyperpituitarism <ul><li>10% of intracranial neoplasms </li></ul><ul><li>Incidental findings in autopsies – 25% </li></ul><ul><li>3% of cases are assoc. with MEN type 1 </li></ul><ul><li>Microadenomas = less than 1 cm </li></ul><ul><li>Macroadenomas = more than 1 cm </li></ul>
  8. 12. Genetic abnormalities associated with Pituitary adenomas <ul><li>Monoclonal in origin </li></ul><ul><ul><ul><li>From a single somatic cell </li></ul></ul></ul><ul><li>G-protein mutations </li></ul><ul><ul><ul><li>Role in signal transduction </li></ul></ul></ul><ul><ul><ul><li>Best characterized molecular abnormalities </li></ul></ul></ul><ul><li>Association with MEN syndrome </li></ul><ul><ul><ul><li>MEN1 gene on chromosome 11q13 </li></ul></ul></ul><ul><li>Mutations of the RAS oncogene and overexpression of the c-MYC oncogene </li></ul><ul><ul><ul><li>Aggressive or advanced pituitary adenomas </li></ul></ul></ul>
  9. 14. Pituitary adenoma - Morphology <ul><li>Soft, well-circumscribed lesion confined to the sella turcica </li></ul><ul><ul><ul><li>Larger lesions extend into the suprasellar region, compress the optic chiasm and adjacent structures </li></ul></ul></ul><ul><ul><ul><li>30% of cases extend into the cavernous and sphenoid sinuses </li></ul></ul></ul><ul><ul><ul><li>Not grossly encapsulated and infiltrate adjacent bone, dura, and rarely the brain and has no ability for distant metastasis (invasive adenoma) </li></ul></ul></ul><ul><ul><ul><li>Foci of hemorrhage and necrosis are common in larger adenomas </li></ul></ul></ul>
  10. 15. Pituitary adenoma - Morphology <ul><li>Composed of relatively uniform, polygonal cells arrayed in sheets or cords </li></ul><ul><li>Nuclei may be uniform or pleiomorphic </li></ul><ul><li>Modest mitotic activity </li></ul><ul><li>Cytoplasm maybe acidophilic, basophilic, or chromophobic </li></ul>
  11. 16. Prolactinoma <ul><li>Lactotroph adenomas </li></ul><ul><li>Comprising about 30% </li></ul><ul><li>Majority are weakly acidophilic or chromophobic (sparsely granulated prolactinoma); rare are strongly acidophilic (densely granulated prolactinoma) </li></ul><ul><li>Undergo dystrophic calcification </li></ul><ul><ul><ul><li>Psammoma bodies </li></ul></ul></ul><ul><ul><ul><li>“ pituitary stone” </li></ul></ul></ul>
  12. 20. Prolactinoma <ul><li>Prolactinemia – increase prolactin level </li></ul><ul><ul><ul><li>Amenorrhea, galactorrhea, loss of libido, and infertility </li></ul></ul></ul><ul><li>Physiologic prolactinemia </li></ul><ul><ul><ul><li>Pregnancy, suckling in lactating women, stress </li></ul></ul></ul><ul><li>Pathologic prolactinemia </li></ul><ul><ul><ul><li>Lactotroph hyperplasia – interference with normal dopamine inhibition of prolactin </li></ul></ul></ul><ul><li>STALK EFFECT – any mass in the suprasellar compartment may disturb the normal inhibitory influence of the hypothalamus on prolactin secretion resulting in hyperprolactinemia </li></ul><ul><li>*** Therefore, a mild elevation in serum prolactin in a patient with a pituitary adenoma does not necessarily indicate a prolactin-secreting tumor. </li></ul>
  13. 21. Prolactinoma <ul><li>Other causes of hyperprolactinemia </li></ul><ul><ul><ul><li>Drugs – neuroleptic (phenothiazines, haloperidol), anti-hypertensive (reserpine) </li></ul></ul></ul><ul><ul><ul><li>Estrogens </li></ul></ul></ul><ul><ul><ul><li>Renal failure </li></ul></ul></ul><ul><ul><ul><li>hypothyroidism </li></ul></ul></ul><ul><li>Treatment : surgery or with Bromocriptine, a dopamine receptor agonist </li></ul>
  14. 22. Growth Hormone (Somatotroph cell) Adenomas <ul><li>2 nd most common type of functioning pituitary adenomas </li></ul><ul><li>Express a mutant GTPase-deficient alpha-subunit of the G-protein </li></ul><ul><li>Histology </li></ul><ul><ul><li>Densely granulated </li></ul></ul><ul><ul><ul><li>Cells are monomorphic and acidophilic </li></ul></ul></ul><ul><ul><li>Sparsely granulated </li></ul></ul><ul><ul><ul><li>Composed of chromophobe cells </li></ul></ul></ul>
  15. 23. Growth Hormone (Somatotroph cell) Adenomas <ul><li>Mammosomatotroph adenomas </li></ul><ul><ul><ul><li>Bihormonal </li></ul></ul></ul><ul><ul><ul><li>Reactive for both GH and prolactin </li></ul></ul></ul><ul><li>Persistent hypersecretion of GH stimulates the hepatic secretion of insulin-like growth factor (IGF-I or somatomedin C) </li></ul><ul><ul><ul><li>Responsible for many clinical manifestations </li></ul></ul></ul>
  16. 24. Growth Hormone (Somatotroph cell) Adenomas <ul><li>Clinical manifestations </li></ul><ul><ul><li>Gigantism </li></ul></ul><ul><ul><ul><li>Appears in children before epiphyseal closure </li></ul></ul></ul><ul><ul><ul><li>Genralized increase in body size with disproportionately long arms and legs </li></ul></ul></ul><ul><ul><li>Acromegaly </li></ul></ul><ul><ul><ul><li>Increased levels of GHvare present after closure of the epiphysis </li></ul></ul></ul><ul><ul><ul><li>Affects the skin and soft tissues; viscera (thyroid, heart, liver, and adrenals); bones of the face, hands, and feet </li></ul></ul></ul>
  17. 25. Growth Hormone (Somatotroph cell) Adenomas <ul><li>ACROMEGALY </li></ul><ul><ul><ul><li>Increased bone density (hyperostosis) in both the spine and hips </li></ul></ul></ul><ul><ul><ul><li>Enlargement of the jaw results in protrusion (prognathism) with broadening of the lower face </li></ul></ul></ul><ul><ul><ul><li>Enlarged hands and feet with broad sausage-like fingers </li></ul></ul></ul>
  18. 34. Growth Hormone (Somatotroph cell) Adenomas <ul><li>Diagnosis </li></ul><ul><ul><ul><li>Elevated serum GH and IGF-I levels </li></ul></ul></ul><ul><ul><ul><li>Failure to suppress GH production in response to an oral load glucose is one of the most sensitive test for acromegaly </li></ul></ul></ul><ul><li>Treatment </li></ul><ul><ul><ul><li>Restore GH levels to normal and to decrease symptoms </li></ul></ul></ul><ul><ul><ul><li>Surgery, radiation therapy, or by drug therapy </li></ul></ul></ul>
  19. 38. Corticotroph Cell Adenomas <ul><li>Usually small microadenomas </li></ul><ul><li>Most often basophilic and occasionally chromophobic </li></ul><ul><li>Stain positively with PAS due to POMC </li></ul><ul><li>Immunoreactivity for POMC and its derivatives – ACTH and beta-endorphin </li></ul><ul><li>Leads to adrenal hypersecretion of cortisol leading to hypercortisolism (Cushing syndrome) </li></ul>
  20. 39. Corticotroph Cell Adenomas <ul><li>Cushing disease </li></ul><ul><ul><ul><li>Pituitary Cushing </li></ul></ul></ul><ul><li>Nelson syndrome </li></ul><ul><ul><ul><li>Large destructive adenomas developing in patients after surgical removal of the adrenal glands for treatment of Cushing syndrome </li></ul></ul></ul><ul><ul><ul><li>Due to loss of the inhibitory effect of adrenal corticosteroids on a pre-existing corticotroph microadenoma </li></ul></ul></ul><ul><ul><ul><li>Hypercortisolism is absent </li></ul></ul></ul>
  21. 40. Gonadotroph (LH-producing and FSH-producing) Adenomas <ul><li>Usually found in middle-aged men and women with neurologic symptoms </li></ul><ul><li>Causes decreased energy and libido in men and amenorrhea in pre-menopausal women </li></ul><ul><ul><ul><li>Secondary gonadal hypofunction </li></ul></ul></ul>
  22. 41. Thyrotroph (TSH-producing) Adenomas <ul><li>Rare, accounting for about 1% of all pituitary adenomas </li></ul><ul><li>Chromophobic or basophilic </li></ul><ul><li>Rare cause of hyperthyroidism </li></ul>
  23. 42. Non-Functioning Pituitary Adenomas <ul><li>Approximately 25% of all pituitary tumors </li></ul><ul><li>Typical presentation is mass effects </li></ul><ul><li>“ null cell adenomas” </li></ul><ul><ul><ul><li>Inability to demonstrate markers of differentiation </li></ul></ul></ul><ul><ul><ul><li>It is now known that most null cell adenomas have biochemical and ultrastructural features that allow their characterization as silent tumors of gonadotrophin lineage </li></ul></ul></ul>
  24. 43. Pituitary Carcinomas <ul><li>Rare </li></ul><ul><li>Most are non-functional </li></ul><ul><li>Diagnosis requires demonstration of metastasis – LN, bone, liver </li></ul>
  25. 44. Hypopituitarism <ul><li>Decreased secretion of pituitary hormones, which result from diseases of the hypothalamus or of the pituitary </li></ul><ul><li>Hypofunction of the anterior pituitary occurs when approximately 75% of the parenchyma is lost or absent </li></ul><ul><li>Hypopituitarism accompanied by evidence of posterior pituitary dysfunction in the form of diabetes insipidus is almost always of hypothalamic origin </li></ul>
  26. 45. Hypopituitarism <ul><li>Causes: </li></ul><ul><ul><ul><li>Tumors and other mass lesions </li></ul></ul></ul><ul><ul><ul><li>Pituitary surgery or radiation </li></ul></ul></ul><ul><ul><ul><li>Pituitary apoplexy </li></ul></ul></ul><ul><ul><ul><li>Ischemic necrosis of the pituitary and Sheehan syndrome </li></ul></ul></ul><ul><ul><ul><li>Rathke cleft cyst </li></ul></ul></ul><ul><ul><ul><li>Empty sella syndrome </li></ul></ul></ul><ul><ul><ul><li>Genetic defects </li></ul></ul></ul>
  27. 46. Hypopituitarism <ul><li>Hypothalamic lesions </li></ul><ul><ul><ul><li>Tumors </li></ul></ul></ul><ul><ul><ul><ul><li>Craniopharyngiomas </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Metastatic lesions (breast and lung) </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Radiation treatment of nasopharyngeal tumors </li></ul></ul></ul></ul><ul><ul><ul><li>Inflammatory disorders and infections </li></ul></ul></ul><ul><ul><ul><ul><li>Sarcoidosis </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Tuberculous meningitis </li></ul></ul></ul></ul>
  28. 55. Posterior Pituitary <ul><li>ADH (Vasopressin) </li></ul><ul><ul><li>Supraoptic nucleus </li></ul></ul><ul><li>Oxytocin </li></ul><ul><ul><li>Paraventricular nucleus </li></ul></ul>
  29. 61. Posterior Pituitary Syndromes <ul><li>Diabetes insipidus </li></ul><ul><ul><ul><li>ADH deficiency </li></ul></ul></ul><ul><ul><ul><li>Characterized by excessive urination (polyuria) </li></ul></ul></ul><ul><ul><ul><li>Central – due to ADH deficiency </li></ul></ul></ul><ul><ul><ul><li>Nephrogenic – renal tubular unresponsiveness to circulating ADH </li></ul></ul></ul><ul><ul><ul><li>Excretion of large volume of dilute urine with low specific gravity </li></ul></ul></ul><ul><ul><ul><li>Increased serum sodium and osmolality </li></ul></ul></ul><ul><ul><ul><li>Causes: head trauma, tumors and inflammatory conditions involving the hypothalamus </li></ul></ul></ul>
  30. 64. Posterior Pituitary Syndromes <ul><li>Syndrome of Inappropriate ADH (SIADH) secretion </li></ul><ul><ul><ul><li>ADH excess causes resorption of excessive amounts of free water, resulting in hyponatremia </li></ul></ul></ul><ul><ul><ul><li>Clinical manifestations – hyponatremia, cerebral edema, and resultant neurologic dysfunction </li></ul></ul></ul><ul><ul><ul><li>Causes: secretion of ectopic ADH by malignant neoplasms (small cell Ca of the lung), local injury to the hypothalamus or posterior pituitary or both </li></ul></ul></ul>
  31. 69. Hypothalamic Suprasellar Tumors <ul><li>May induce hypofunction or hyperfunction of the anterior pituitary, diabetes insipidus, or both </li></ul><ul><li>Mostly are gliomas (chiasm) and craniopharyngiomas </li></ul>
  32. 70. Hypothalamic Suprasellar Tumors <ul><li>Craniopharyngiomas </li></ul><ul><ul><ul><li>Derived from vestigial remnants of Rathke pouch </li></ul></ul></ul><ul><ul><ul><li>Account for 1-5% of intracranial tumors </li></ul></ul></ul><ul><ul><ul><li>Bimodal age distribution </li></ul></ul></ul><ul><ul><ul><ul><ul><li>Childhood (5-15 years) – endocrine deficiencies </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Adults (sixth decade or older) – visual disturbances </li></ul></ul></ul></ul></ul><ul><ul><ul><li>Encapsulated, solid but more commonly cystic and multiloculated </li></ul></ul></ul><ul><ul><ul><li>Encroach on the optic chiasm and cranial nerves </li></ul></ul></ul>
  33. 71. Hypothalamic Suprasellar Tumors <ul><li>Adamantinomatous craniopharyngiomas </li></ul><ul><ul><ul><li>Presents with radiographic calcifications </li></ul></ul></ul><ul><ul><ul><li>Consists of nests and cords of stratifies squamous epithelium </li></ul></ul></ul><ul><ul><ul><li>Compact, lamellar keratin formation (“wet keratin”) </li></ul></ul></ul><ul><ul><ul><li>Tumors extend fingerlets of epithelium into adjacent brain eliciting a brisk glial reaction </li></ul></ul></ul><ul><li>Papillary craniopharyngioma </li></ul><ul><ul><ul><li>Contain both solid sheets and papillae lined by well-differentiated squamous epithelium </li></ul></ul></ul><ul><ul><ul><li>Tumors lack keratin, cyst, and calcification </li></ul></ul></ul>
  34. 75. Thyroid Gland <ul><li>15-20 grams </li></ul><ul><li>Consists of two bulky lateral lobes connected in the midline by a thin isthmus </li></ul><ul><li>Located below and anterior to the larynx </li></ul>
  35. 76. Hyperthyroidism <ul><li>Thyrotoxicosis </li></ul><ul><li>Hypermetabolic state caused by elevated circulating levels of free T3 and T4 </li></ul><ul><li>Most common causes </li></ul><ul><ul><ul><li>Diffuse hyperplasia of the thyroid associated with Graves disease (85% of cases) </li></ul></ul></ul><ul><ul><ul><li>Hyperfunctional multinodular goiter </li></ul></ul></ul><ul><ul><ul><li>Hyperfunctional adenoma of the thyroid </li></ul></ul></ul>
  36. 77. Hyperthyroidism <ul><ul><ul><li>Neuromuscular system </li></ul></ul></ul><ul><ul><ul><ul><ul><li>Tremors, hyperactivity, emotional lability, anxiety, inability to concentrate, insomnia </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Thyroid myopathy – proximal muscle weakness with decrease muscle mass </li></ul></ul></ul></ul></ul><ul><ul><ul><li>Ocular changes </li></ul></ul></ul><ul><ul><ul><ul><ul><li>Wide, staring gaze and lid lag </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Thyroid ophthalmopathy </li></ul></ul></ul></ul></ul><ul><ul><ul><li>Gastrointestinal system </li></ul></ul></ul><ul><ul><ul><ul><ul><li>Hypermotility, malabsorption, and diarrhea </li></ul></ul></ul></ul></ul><ul><ul><ul><li>Skeletal system </li></ul></ul></ul><ul><ul><ul><ul><ul><li>Stimulates bone resorption (inc. porosity of cortical bone and reduced volume of trabecular bone) </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Osteoporosis and increased risk of fractures </li></ul></ul></ul></ul></ul>
  37. 78. Hyperthyroidism <ul><li>Thyroid storm </li></ul><ul><ul><ul><li>Abrupt onset of hyperthyroidism </li></ul></ul></ul><ul><ul><ul><li>Occurs most commonly in patients with Graves disease – acute elevation of catecholamine levels </li></ul></ul></ul><ul><ul><ul><li>A medical emergency </li></ul></ul></ul><ul><ul><ul><li>Untreated patients die of cardiac arrhythmias </li></ul></ul></ul><ul><li>Apathetic hyperthyroidism </li></ul><ul><ul><ul><li>Thyrotoxicosis occuring in the elderly </li></ul></ul></ul>
  38. 79. Hyperthyroidism <ul><li>Diagnosis </li></ul><ul><ul><ul><li>Laboratory measurement of TSH, FT3, FT4 </li></ul></ul></ul><ul><ul><ul><li>RAIU </li></ul></ul></ul><ul><ul><ul><li>TRH stimulation test </li></ul></ul></ul><ul><ul><ul><ul><ul><li>Used in suspected hyperthyroidism where results of TSH are unequivocal </li></ul></ul></ul></ul></ul>
  39. 82. Graves Disease <ul><li>Most common cause of endogenous hyperthyroidism </li></ul><ul><li>Triad: </li></ul><ul><ul><li>Hyperthyroidism </li></ul></ul><ul><ul><li>Infiltrative ophthalmopathy with resultant exophthalmos </li></ul></ul><ul><ul><li>Localized, infiltrative dermopathy (pretibial myxedema) </li></ul></ul>
  40. 83. Graves Disease <ul><li>An autoimmune disorder with a variety of antibodies </li></ul><ul><ul><li>Thyroid-stimulating immunoglobulin (TSI) </li></ul></ul><ul><ul><li>Thyroid growth-stimulating immunoglobulins (TGI) </li></ul></ul><ul><ul><li>TSH-binding inhibitor immunoglobulins (TBII) </li></ul></ul><ul><li>Gland is symmetrically enlarged because of diffuse hypertrophy and hyperplasia </li></ul>
  41. 96. Hypothyroidism <ul><li>Structural or functional derangement that interfere with the production of afequate levels of thyroid hormone </li></ul><ul><li>Primary, secondary, or tertiary </li></ul>
  42. 98. Cretinism <ul><li>Hypothyroidism that occurs in infancy or early childhood </li></ul><ul><li>Impaired development of the skeletal system and CNS </li></ul><ul><li>Manifests as severe mental retardation, short stature, coarse facial features, protruding tongue and umbilical hernia </li></ul>
  43. 99. Myxedema <ul><li>Hypothyroidism developing in the older child or adult </li></ul><ul><li>Gull disease </li></ul><ul><li>Characterized by slowing of physical and mental activity </li></ul><ul><li>Accumulation of matrix substances (glycosaminoglycans and hyaluronic acid) in the skin, subcutaneous tissues, and visceral sites  edema, broadening and coarsening of facial features, enlargement of the tongue, and deepening of the voice </li></ul><ul><li>Measurement of serum TSH level is the most sensitive screening test </li></ul>
  44. 102. Hashimoto Thyroiditis <ul><li>Chronic lymphocytic thyroiditis </li></ul><ul><li>Struma lymphomatosa </li></ul><ul><li>Most common cause of hypothyroidism in areas of the world where iodine levels are sufficient </li></ul><ul><li>Pathogenesis: </li></ul><ul><ul><li>CD8+ cytotoxic T-cell mediated cell death </li></ul></ul><ul><ul><li>Cytokine mediated cell death </li></ul></ul><ul><ul><li>Binding of anti-thyroid Ab’s  ADCC </li></ul></ul><ul><ul><ul><li>Anti-TSH receptor Ab’s, antithyroglobulin, antithyroid peroxidase Ab’s </li></ul></ul></ul>
  45. 104. Hashimoto Thyroiditis <ul><li>Morphology </li></ul><ul><ul><li>Diffusely enlarge thyroid </li></ul></ul><ul><ul><li>Microscopic examination show extensive infiltration of the parenhyma by a mononuclear inflammatory infiltrate containing small lymphocytes, plasma cells, and well developed germinal centers, Hurtle cell metaplasia </li></ul></ul><ul><ul><li>Fibrous variant – “keloid-like” </li></ul></ul>
  46. 106. Subacute (Granulomatous) Thyroiditis <ul><li>De Quervain thyroiditis </li></ul><ul><li>Caused by viral infection or postviral inflammatory process </li></ul><ul><li>Multinucleated giant cells are seen </li></ul>
  47. 108. Subacute Lymphocytic (painless) Thyroiditis <ul><li>Painless thyroiditis or silent thyroiditis </li></ul><ul><li>Uncommon cause of hyperthyroidism </li></ul><ul><li>More common in women, especially during the post-partum period (postpartum thyroiditis) </li></ul><ul><li>Lymphocytic infiltration with hyperplastic germinal centers within the thyroid parenchyma and patch disruption and collapse of thyroid follicles </li></ul>
  48. 109. Riedel Thyroiditis <ul><li>Rare disorder of unknown etiology </li></ul><ul><li>Extensive fibrosis involving the thyroid and contiguous neck structures </li></ul><ul><li>Hard and fixed thyroid mass </li></ul>
  49. 110. Diffuse and Multinodular Goiters <ul><li>Reflect impaired synthesis of thyroid hormones </li></ul><ul><li>Diffuse nontoxic (simple) goiter </li></ul><ul><ul><li>Diffusely involves the entire gland without producing nodularity </li></ul></ul><ul><ul><li>Enlarged follicles are filled with colloid = colloid goiter </li></ul></ul><ul><li>Multinodular goiter </li></ul><ul><ul><li>Irregular enlargement of the gland </li></ul></ul><ul><ul><li>Produce the most extreme enlargement and are more mistaken for neoplastic involvement than any other form of thyroid disease </li></ul></ul>
  50. 112. Neoplasms of the Thyroid <ul><li>Clue to the nature of a thyroid nodule </li></ul><ul><ul><ul><li>Solitary nodules , in general are more likely to be neoplastic than are multiple nodules </li></ul></ul></ul><ul><ul><ul><li>Nodules in younger patients are more likely to be neoplastic than are those in older patients </li></ul></ul></ul><ul><ul><ul><li>A history of radiation treatment to the head and neck region is associated with an increased incidence of thyroid malignancy </li></ul></ul></ul><ul><ul><ul><li>Nodules that take up radioactive iodine in imaging studies (hot nodules) are more likely to be benign than malignant </li></ul></ul></ul>
  51. 113. Adenomas <ul><li>Discrete, solitary masses </li></ul><ul><li>Derived from follicular epithelium </li></ul><ul><ul><ul><li>Follicular adenomas </li></ul></ul></ul><ul><li>Classification based on the degree of follicle formation and the colloid content of the follicles </li></ul><ul><li>Majority are nonfunctional </li></ul><ul><li>“ Toxic adenomas” </li></ul><ul><ul><ul><li>Hormone production is independent of TSH stimulation </li></ul></ul></ul><ul><ul><ul><li>Thyroid autonomy </li></ul></ul></ul>
  52. 114. Adenomas <ul><li>Morphology </li></ul><ul><ul><ul><li>Solitary, spherical, encapsulated lesion that is well demarcated from the surrounding thyroid parenchyma </li></ul></ul></ul><ul><ul><ul><li>Lesion bulges from the cut surface and compresses the adjacent thyroid </li></ul></ul></ul><ul><ul><ul><li>Microscopically show cells often form uniform-appearing follicles that contain colloid </li></ul></ul></ul>
  53. 117. Adenomas <ul><li>Hurthle cell adenoma </li></ul><ul><ul><ul><li>Neoplastic cells acquire brightly eosinophilic granular cytoplasm (oxyphil or hurthle cell change) </li></ul></ul></ul><ul><ul><ul><li>Clinical presentation and behavior is similar to conventional adenomas </li></ul></ul></ul><ul><ul><ul><li>**** Careful evaluation of the integrity of the capsule is therefore critical in distinguishing follicular adenomas from follicular carcinomas </li></ul></ul></ul><ul><ul><ul><li>*** Owing to the need for evaluating capsular integrity, the definitive diagnosis of adenomas can be made only after careful histologic examination of the resected specimen </li></ul></ul></ul>
  54. 120. Thyroid Neoplasms <ul><li>Papillary carcinoma – 75-85% of cases </li></ul><ul><li>Follicular carcinoma – 10-20% of cases </li></ul><ul><li>Medullary carcinoma – 5% of cases </li></ul><ul><li>Anaplastic carcinoma - <5% of cases </li></ul><ul><ul><ul><ul><ul><li>Robbins and Cotran, 7 th Edition </li></ul></ul></ul></ul></ul>
  55. 125. Papillary Carcinoma <ul><li>Associated with previous exposure to ionizing radiation </li></ul><ul><li>Contain branching papillae with fibrovascular stalk </li></ul><ul><li>Nuclei imparts an optically clear or empty appearance (ground glass or Orphan Annie eye) </li></ul><ul><li>Presence of psammoma bodies </li></ul><ul><li>Lymphatic invasion </li></ul>
  56. 128. Follicular Carcinoma <ul><li>Peak incidence : 40’s and 50’s </li></ul><ul><li>Increased in areas of dietary iodine deficiency </li></ul><ul><li>High frequency of RAS mutations </li></ul><ul><li>Composed of fairly uniform cells forming small follicles containing colloid </li></ul><ul><li>Vascular invasion is common </li></ul>
  57. 135. Medullary Carcinoma <ul><li>Neuroendocrine neoplasms derived from parafollicular cells or C cells of the thyroid (calcitonin) </li></ul><ul><li>Component of MEN syndrome 2A or 2B </li></ul><ul><li>Bilaterality and multicentricity are common </li></ul><ul><li>Composed of polygonal to spindle shaped cells forming nests, trabeculae, and even follicles </li></ul><ul><li>Amyloid deposits are present in the adjacent stroma </li></ul><ul><li>Presence of multicentric C-cell hyperplasia </li></ul>
  58. 139. Anaplastic Carcinoma <ul><li>Undifferentiated tumors of the thyroid follicular epithelium </li></ul><ul><li>Composed of highly anaplastic cells </li></ul><ul><ul><li>Large pleomorphic giant cells (osteoclast-like multinucleated giant cells) </li></ul></ul><ul><ul><li>Spindle cells with a sarcomatous appearance </li></ul></ul><ul><ul><li>Mixed spindle and giant cells </li></ul></ul><ul><ul><li>Small cells resembling those of small cell Ca </li></ul></ul>
  59. 144. Congenital Anomalies <ul><li>Thyroglossal duct or cyst </li></ul><ul><ul><ul><li>Most common </li></ul></ul></ul><ul><ul><ul><li>A persistent sinus tract may remain as a vestigial remnant of the tubular development of the thyroid gland </li></ul></ul></ul><ul><ul><ul><li>Occur at any age and manifest until adult life </li></ul></ul></ul><ul><ul><ul><li>Cysts contains mucinous, or clear secretions and rarely over 2-3 cm in diameter </li></ul></ul></ul><ul><ul><ul><li>Present in the midline of the neck anterior to the trachea </li></ul></ul></ul><ul><ul><ul><li>Lined by stratified squamous epithelium and subjacent to this is an intense lymphocytic infiltrate </li></ul></ul></ul><ul><ul><ul><li>Superimposed infection may occur (abscess cavities), and rarely give rise to cancers </li></ul></ul></ul>
  61. 147. <ul><li>WEIGHS 35-40 MG </li></ul><ul><li>Yellow-brown, ovoid encapsulated nodule </li></ul><ul><li>Most are composed of chief cells; contain PTH </li></ul><ul><li>Activity is controlled by the level of free (ionized) calcium </li></ul>
  62. 148. Primary Hyperparathyroidism <ul><li>Causes hypercalcemia </li></ul><ul><li>Adenoma – 75-80% </li></ul><ul><li>Primary hyperplasia (diffuse or nodular) 10-15% </li></ul><ul><li>Parathyroid carcinoma - <5% </li></ul><ul><li>Associated with MEN 1 & 2, Familial hypocalciuric hypercalcemia (FHH) </li></ul><ul><li>Skeletal changes : osteitis fibrosa cystica </li></ul>
  63. 152. Symptomatic Primary Hyperparathyroidism <ul><li>Bone disease </li></ul><ul><li>Nephrolithiasis </li></ul><ul><li>GIT disturbances – constipation, nausea, peptic ulcers, pancreatitis, gallstones </li></ul><ul><li>CNS alterations – depression, lethargy, seizures </li></ul><ul><li>Neuromuscular abnormalities – weakness and fatigue </li></ul><ul><li>Cardiac manifestations – aortic or mitral valve calcifications </li></ul>
  64. 158. Secondary Hyperparathyroidism <ul><li>Most common cause is RENAL FAILURE </li></ul><ul><li>Others : inadequate dietary calcium, steatorrhea, Vitamin D deficiency </li></ul><ul><li>Glands are hyperplastic with increased number of chief cells or cells with abundant, clear cytoplasm (clear-water cells) </li></ul><ul><li>Bone changes similar to primary type </li></ul><ul><li>Metastatic calcification may be seen in many tissues </li></ul>
  65. 159. Hypoparathyroidism <ul><li>Surgically induced </li></ul><ul><li>Congenital absence </li></ul><ul><li>Familial hypothyroidism </li></ul><ul><ul><li>Associated with chronic mucocutaneous candidiasis and primary adrenal insufficiency </li></ul></ul><ul><ul><li>Known as autoimmune polyendocrine syndrome type I (APS I) </li></ul></ul><ul><ul><li>Mutations in the autoimmune regulator (AIRE) gene </li></ul></ul><ul><li>Idiopathic hypothyroidism </li></ul>
  66. 160. Hypoparathyroidism <ul><li>Clinical presentations </li></ul><ul><ul><ul><li>Tetany – neuromuscular irritability </li></ul></ul></ul><ul><ul><ul><li>Mental status changes emotional instability, anxiety, and depression, confusional states, hallucinations and psychosis </li></ul></ul></ul><ul><ul><ul><li>Intracranial manifestations – calcification of the basal ganglia, parkinson-like movement disorders, increase ICP </li></ul></ul></ul><ul><ul><ul><li>Ocular disease – cataract formation </li></ul></ul></ul><ul><ul><ul><li>CV manifestations prolongation of QT interval </li></ul></ul></ul><ul><ul><ul><li>Dental abnormalities – dental hypoplasia, failure of dental eruption, defective enamel and root formation, abraded carious teeth </li></ul></ul></ul>
  67. 162. Pseudohypoparathyroidism <ul><li>End-organ unresponsiveness to PTH </li></ul><ul><li>Serum PTH levels are normal or elevated </li></ul><ul><li>Pseudohypoparathyroidism Type IA </li></ul><ul><ul><ul><li>Associated with multihormone resistance (PTH, TSH, & FSH/LH) and Albright hereditary osteodystrophy (AHO) </li></ul></ul></ul><ul><ul><ul><li>Short stature, obesity, short metacarpal and metatarsal bones, and variable mental deficits </li></ul></ul></ul><ul><ul><ul><li>Hypocalcemia, hyperphosphatemia, and elevated circulating PTH </li></ul></ul></ul><ul><ul><ul><li>TSH resistance is mild; LH/FSH resistance manifests as hypogonadotrophic hypogonadism in females </li></ul></ul></ul><ul><ul><ul><li>Mutation is inherited on the maternal allele </li></ul></ul></ul>
  68. 163. Pseudohypoparathyroidism <ul><li>Pseudopseudohypoparathyroidism </li></ul><ul><ul><ul><li>Mutation is inherited on the paternal allele </li></ul></ul></ul><ul><ul><ul><li>Characterized by AHO without accompanying multihormonal resistance </li></ul></ul></ul><ul><ul><ul><li>Normal serum calcium, phosphate, and PTH </li></ul></ul></ul>
  70. 167. <ul><li>4 grams </li></ul><ul><li>Adrenal cortex </li></ul><ul><ul><li>Glucocorticoids (cortisol) – ZF + ZR </li></ul></ul><ul><ul><li>Mineralocorticoids (aldosterone) – ZG </li></ul></ul><ul><ul><li>Sex steroids (estrogens and androgens) - ZR </li></ul></ul><ul><li>Adrenal medulla </li></ul><ul><ul><li>Composed of chromaffin cells </li></ul></ul><ul><ul><li>catecholamines </li></ul></ul>
  71. 172. Hypercortisolism (Cushing syndrome) <ul><li>70-80% - results from primary hypersecretion of ACTH </li></ul><ul><li>10-20% - primary adrenal neoplasms and primary cortical hyperplasia </li></ul><ul><li>About 10% - ectopic </li></ul><ul><li>Cushing disease – pituitary form </li></ul>
  72. 174. Hypercortisolism (Cushing syndrome) <ul><li>Crooke hyaline change – pituitary </li></ul><ul><li>Adrenals </li></ul><ul><ul><li>Cortical atrophy </li></ul></ul><ul><ul><li>Diffuse hyperplasia – found in 60-70% </li></ul></ul><ul><ul><li>Nodular hyperplasia </li></ul></ul><ul><ul><li>An adenoma </li></ul></ul>
  73. 187. Primary Hyperaldosteronism <ul><li>Chronic excess aldosterone secretion  sodium retention and potassium excretion with resultant HPN and hypokalemia </li></ul><ul><li>Causes: </li></ul><ul><ul><li>Adrenocortical neoplasm – most common </li></ul></ul><ul><ul><ul><li>Conn syndrome – adult middle life; W>M </li></ul></ul></ul><ul><ul><li>Primary adrenocortical hyperplasia (idiopathic hyperaldosteronism) </li></ul></ul><ul><ul><li>Glucocorticoid-remediable hyperaldosteronism – familial and genetic </li></ul></ul>
  75. 197. Congenital Adrenal Hyperplasia <ul><li>Autosomal recessive </li></ul><ul><li>Results in virilization </li></ul><ul><li>Salt wasting </li></ul><ul><li>21-Hydroxylase deficiency – most common </li></ul>
  76. 199. Congenital Adrenal Hyperplasia <ul><li>Morphology </li></ul><ul><ul><ul><li>Adrenal are bilaterally hyperplastic – 10-15X </li></ul></ul></ul><ul><ul><ul><li>Adrenal cortex is thickened and nodular </li></ul></ul></ul><ul><ul><ul><li>On cut section, the widened cortex appears brown owing to total depletion of all lipids </li></ul></ul></ul><ul><ul><ul><li>Hyperplasia of corticotroph (ACTH-producing) cells is present in the anterior pituitary </li></ul></ul></ul>
  77. 200. Adrenal Insufficiency <ul><li>Caused by either primary adrenal disease (primary hypoadrenalism) or decreased stimulation of the adrenals owing to a deficiency of ACTH (secondary hypoadrenalism) </li></ul><ul><li>Patterns </li></ul><ul><ul><ul><li>Primary acute adrenocortical insufficiency (adrenal crisis) </li></ul></ul></ul><ul><ul><ul><li>Primary chronic adrenocortical insufficiency (Addison disease) </li></ul></ul></ul><ul><ul><ul><li>Secondary adrenocortical insufficiency </li></ul></ul></ul>
  78. 202. Primary Acute Adrenocortical Insufficiency <ul><li>As a crisis  gland is incapable of responding </li></ul><ul><li>Patients maintained on exogenous corticosteroids  rapid withdrawal or failure to increase dose when there is increase requirement </li></ul><ul><li>As a result of massive adrenal hemorrhage  destruction of the adrenal cortex </li></ul>
  79. 203. Waterhouse-Friderichsen Syndrome <ul><li>Associated with Neisseria meningitides causing overwhelming bacterial infection (others : Pneumococci, Pseudomonas, Haemophilus, staphylococcus </li></ul><ul><li>Rapidly progressive hypotension  shock </li></ul><ul><li>DIC </li></ul><ul><li>Adrenocortical insufficiency with massive bilateral adrenal hemorrhage </li></ul><ul><li>*** The adrenals are converted to sacs of clotted blood virtually obscuring all underlying detail </li></ul>
  80. 206. Primary Chronic Adrenocortical Insufficiency (Addison Disease) <ul><li>Causes: </li></ul><ul><ul><li>Autoimmune adrenalitis – 60-70% of cases </li></ul></ul><ul><ul><li>Tuberculosis </li></ul></ul><ul><ul><li>AIDS </li></ul></ul><ul><ul><li>Metastatic cancers </li></ul></ul>
  81. 213. Primary Chronic Adrenocortical Insufficiency (Addison Disease) <ul><li>Hyperkalemia, hyponatremia, volume depletion, and hypotension </li></ul><ul><li>Hyperpigmentation of the skin </li></ul><ul><li>GI disturbances </li></ul>
  82. 214. Secondary Adrenocortical Insufficiency <ul><li>Any disorder of the hypothalamus and pituitary – metastatic cancer, infection, infarction, or irradiation that reduces the output of ACTH  hypoadrenalism </li></ul><ul><li>Absence of hyperpigmentation because melanotropic hormone levels are low </li></ul><ul><li>Characterized by deficient cortisol and androgen output but normal or near normal aldosterone synthesis </li></ul><ul><li>Adrenal cortex may be reduced to a thin ribbon composed largely of zona glomerulosa; medulla is unaffected </li></ul>
  83. 215. Adrenocortical Neoplasms <ul><li>Adrenocortical adenomas </li></ul><ul><ul><ul><li>Well-circumscribed nodular lesions up to 2.5 cm in diameter that expands the adrenal </li></ul></ul></ul><ul><ul><ul><li>Functional adenomas are associated with atrophy of the adjacent cortex </li></ul></ul></ul><ul><li>Adrenocortical carcinomas </li></ul><ul><ul><ul><li>Rare; can occur in any age including childhood </li></ul></ul></ul><ul><ul><ul><li>Inherited causes </li></ul></ul></ul><ul><ul><ul><ul><ul><li>Li-Fraumeni syndrome </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Beckwith-Wiedemann syndrome </li></ul></ul></ul></ul></ul><ul><ul><ul><li>Lesions are large, invasive, and efface the native adrenal gland </li></ul></ul></ul>
  84. 220. Pheochromocytoma <ul><li>Adrenal medulla tumors consist of chromaffin cells </li></ul><ul><li>Presents with HPN </li></ul><ul><li>10% arise in association with several familial syndromes </li></ul><ul><li>10% are extra-adrenal </li></ul><ul><li>10% are bilateral </li></ul><ul><li>10% are biologically malignant </li></ul><ul><li>10% arise in childhood </li></ul>
  85. 226. Pineal Gland <ul><li>100-180mg; located between the colliculi </li></ul><ul><li>Pineoblastomas </li></ul><ul><ul><li>First 2 decades of life </li></ul></ul><ul><ul><li>Cytology similar to primitive embryonal tumor </li></ul></ul><ul><ul><li>Spread via the CSF </li></ul></ul><ul><li>Pineocytomas </li></ul><ul><ul><li>Occurs in adults </li></ul></ul>
  86. 227. Thank You!