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PATHOLOGY: Endocrine System (Thyroid (Autoimmune Thyroid Disease (Chronic…

- - - - Adrenal medulla
      - Parathyroid:
      - Thyroid:
    - - NO Primary hyperparathyroidism
      - Extraendocrine manifestations: ganglioneuromas of mucosal sites (GI tract, lips, tongue) and a marfanoid habitus
- - - - Lactotroph Adenomas: Prolactin-secreting lactotroph adenomas most frequent type of hyperfunctioning pituitary adenoma (30%)
      - Somatotroph Adenomas: GH-secreting somatotroph adenomas: second most common type of functioning pituitary adenoma, and cause gigantism in children or acromegaly in adults
    - - Nonfunctioning pituitary adenomas
    - - Pathogenesis
        
        Molecular abnormalities a. w/ aggressive behavior: aberrations in cell cycle checkpoint genes: overexpression of cyclin D1, mutations of TP53, and epigenetic silencing of RB
        
        5% arise as a result of an inherited predisposition; Four genes identified as a cause of familial: MEN1, CDKN1B, PRKAR1A, and AIP
        
        G-protein mutations (one of most common genomic alterations in pituitary adenomas)
    - - gross: well-circumscribed, soft lesion ;30% of cases: nonencapsulated and infiltrate adj bone, dura, and (uncommonly) brain. Foci of hemorrhage and/or necrosis are common in larger adenomas
      - micro: composed of relatively uniform, polygonal cells arrayed in sheets, cords, or papillae; Supporting connective tissue, or reticulin, sparse; This cellular monomorphism and absence of a significant reticulin network distinguish pituitary adenomas from non-neoplastic anterior pituitary parenchyma
      - Adenomas harboring TP53 mutations: brisk mitotic activity and higher prolif rates: designated atypical adenomas bc of potential for aggressive behavior
- - - - most common cause of hypothyroidism in iodine sufficient areas; most: 45-65 yrs, more in women (female to male ratio of 10 : 1 to 20 : 1.)
      - morpho
        
        thyroid diffusely and symmetrically enlarged
        
        widespread infiltration of parenchyma by a mononuclear inflammatory infiltrate (small lymphocytes, plasma cells, and well-developed germinal centers). thyroid follicles atrophic + lined in many areas by epithelial cells distinguished by presence of abundant eosinophilic, granular cytoplasm, termed Hürthle, or oxyphil, cells (a metaplastic response of normal low cuboidal follicular epithelium to injury); Hürthle cells charac by numerous prominent mitC
      - clinical features: hypothyroidism develops gradually. some cases: preceded by transient thyrotoxicosis caused by disruption of thyroid follicles (hashitoxicosis); often have other AI diseases and are at incr risk for B-cell non-Hodgkin lymphomas (typically arise within thyroid). thyroid epithelial cancers remains controversial, some studies suggesting a predisposition to papillary carcinomas
  - - - major subtypes (Most (except medullary carcinomas: parafollicular or c cells) derived from thyroid follicular epithelium)
        
        Papillary carcinoma (>85%)
        
        morpho: Nuclei w/ finely dispersed chromatin--> optically clear or empty appearance--> ground-glass or Orphan Annie eye nuclei. invaginations of cytoplasm--> appearance of intranuclear inclusions (“pseudo-inclusions”) or intranuclear grooves; These nuclear features sufficient for diagnosis of papillary carcinoma, even in absence of papillary architecture
        
        Follicular carcinoma (5% to 15%)
        
        morpho: distinction betw follicular adenoma + carcinoma: extensive histologic sampling of tumor capsule–thyroid interface, to exclude capsular and/or vascular invasion
        
        Anaplastic (undifferentiated) carcinoma (<5%)
        
        morpho: bulky masses that typically grow rapidly beyond thyroid capsule into adjacent neck structures. highly anaplastic cells, lots of mitosis
        
        mortality rate 100%. mean age of 65. 1/4 have a hx of a well-differentiated thyroid carcinoma; grow with wild abandon despite therapy. Metastases common, but most death occurs in less than 1 year as a result of aggressive local growth and compromise of vital structures in the neck
        
        Medullary carcinoma (5%)
        
        morpho: Amyloid deposits, derived from altered calcitonin molecules, present in adj stroma in many cases + a distinctive feature;
- - - - Primary hyperplasia (diffuse or nodular)—5% to 10%: typically multiglandular ; most common pattern: chief cell hyperplasia. Less commonly, constituent cells contain abundant clear cytoplasm as a consequence of accumulation of glycogen—a condition designated water-clear cell hyperplasia
      - Parathyroid carcinoma—1%: enlarge one gland; may exceed 10gr; diagnosis of carcinoma based on cytologic detail unreliable; invasion of surrounding tissues and metastasis are only definitive criteria
      - Adenoma—85% to 95%: By definition confined to a single gland; Most weigh 0.5-5gr; Cells w/ bizarre and pleomorphic nuclei often seen (so-called “endocrine atypia”) and must not be taken as a sign of malignancy;
      - Morphologic changes in other organs
        
        Renal
        
        Metastatic calcification
        
        Skeletal changes: more severe cases: cortex grossly thinned + bone marrow contains incr amounts of fibrous tissue accompanied by foci of hemorrhage and cysts (osteitis fibrosa cystica); Aggregates of osteoclasts, reactive giant cells, and hemorrhagic debris occasionally form masses mistaken for neoplasms (brown tumors of hyperparathyroidism)
- - - - Primary hypothalamic-pituitary diseases associated with hypersecretion of ACTH
      - Secretion of ectopic ACTH by nonpituitary neoplasms
      - Primary adrenocortical neoplasms (adenoma or carcinoma) and, rarely, primary cortical hyperplasia
      - majority result of exogenous glucocorticoids (iatrogenic); bilateral cortical atrophy
      - Fig. 20.34