• Excess cortisol for any reason
  
• Pituitary gland changes: Crooke hyaline change-basophilic cytoplasm of ACTH producing cells changes from granular to homogenous, due to accumulation of intermediate filaments
  
• Adrenal gland changes: exogenous cortisol causes low ACTH, which causes atrophy of fasciculata and reticularis, not glomerulosa, in residual or opposite adrenal gland
  
• Causes: (a) exogenous glucocorticoids, (b) small ACTH-producing pituitary adenoma or hyperplasia (most common endogenous cause), (c) adrenal adenoma, adrenal carcinoma or bilateral adrenal hyperplasia, (d) ectopic ACTH production by non-adrenal neoplasm, (e) rarely caused by tumors producing cortisol releasing factor
  

• Most cases
  

• Called Cushing’s disease (Harvey Cushing observed pituitary adenomas associated with hypercortisolism in 1932)
  
• Adrenals usually exhibit nodular or diffuse hyperplasia, have increased weight and rounded contours; outer cortical layers are yellow, inner layers tan-brown; nodules are often multiple, associated with hyperplastic cortex
  
• Zona glomerulosa is difficult to identify in adults, fasciculata has lipid-depleted cells and reticularis cells are vacuolated
  
• Elevated serum ACTH, cortisol and its precursors
  
• Can suppress ACTH with high, but not low dose dexamethasone
  
• Treatment: surgical resection or radiation of pituitary tumor; surgical or medical (with mitotane) adrenalectomy
  

• 25% of endogenous cases; also called ACTH-independent Cushing’s syndrome
  
• 80% are women
  
• Children have more carcinomas than adenomas, produce more hypercortisolism
  
• Adults have similar frequency of adenomas and carcinomas
  
• Virilization: in females-male pattern baldness, clitoromegaly and deepening of voice
  
• Feminization: in males-loss of libido, testicular atrophy and gynecomastia
  
• Large tumors with Cushing’s syndrome or Cushing’s syndrome with obvious virilization and marked 17-ketosteroid excretion are usually carcinomas
  
• High cortisol levels, low ACTH levels
  
• Opposite adrenal gland is atrophic
  
• Cannot suppress or lower ACTH with high or low dose dexamethasone
  

• Tumors secrete ACTH-like substance
  
• In adults, usually due to small cell carcinoma of lung or carcinoid tumor of lung or thymus; also medullary thyroid carcinoma, pancreatic endocrine neoplasm, pheochromocytoma or ovarian tumor
  
• In children, tumors are usually pheochromocytoma, neuroblastoma, thymic or pancreatic endocrine neoplasm
  
• Associated with hypokalemic alkalosis, high urinary excretion of free cortisol, skin pigmentation, edema and severe diabetes mellitus
  
• Usually poor prognosis due to malignant disease
  
• Treatment: resect or treat tumor; control hypercortisolism with aminoglutethimide or other drugs; bilateral adrenalectomy
  
• Gross description: enlarged adrenal glands (total 20-30g) with tan-brown, diffusely hyperplastic cortex
  
• Micro description: diffuse hyperplasia and lipid depletion of fasciculata cells; reticularis cells may exhibit atypia; often accompanied by metastatic tumor
  

• Usually men, age 40-59 years
  
• Elevated serum ACTH, cannot suppress with high or low dose dexamethasone
  

This information is intended for physicians and related personnel, who understand that medical information is often imperfect, and must be interpreted in the context of a patient's clinical data using reasonable medical judgment. This website should not be used as a substitute for the advice of a licensed physician.

All information on this website is protected by copyright of PathologyOutlines.com, Inc. Information from third parties may also be protected by copyright. Please contact us at copyrightPathOut@gmail.com with any questions (click here for other contact information).