Adrenal gland & paraganglia
Adrenal hyperfunction / hyperplasia
Cushing syndrome
Author: Nat Pernick, M.D.
Last author update: 1 February 2013
Last staff update: 3 June 2021
Copyright: 2003-2019, PathologyOutlines.com, Inc.
PubMed Search: Cushing syndrome
Cite this page: Pernick N. Cushing syndrome. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/adrenalcushings.html. Accessed April 20th, 2024.
Definition / general
- 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
Pathophysiology / etiology
- 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
Exogenous glucocorticoids
- Most cases
Small ACTH-producing pituitary adenoma or hyperplasia
- Called Cushing 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
Bilateral adrenal hyperplasia, adrenal adenoma or adrenal carcinoma
- 25% of endogenous cases; also called ACTH-independent Cushing 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 syndrome or Cushing 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
Ectopic ACTH production by non-adrenal neoplasm
- 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
Tumors producing cortisol releasing factor
- Usually men, age 40-59 years
- Elevated serum ACTH, cannot suppress with high or low dose dexamethasone
