Hyperadrenocorticism (Cushing Disease or Syndrome)

• • Due to chronic glucocorticoid excess

  • Facial plethora, dorsocervical fat pad, supraclavicular fat pad, truncal obesity, easy bruisabilility, purple striae, hirsutism, impotence or amenorrhea, muscle weakness, and psychosis

  • Hypertension

  • Hyperglycemia

  • Includes Cushing disease (excess adrenocorticotropic hormone [ACTH] produced by pituitary adenomas) and Cushing syndrome (ectopic ACTH syndrome or primary adrenal disease resulting in glucocorticoid secretion independent of ACTH stimulation)

Epidemiology

• • In children, Cushing syndrome is most commonly caused by adrenal cancers

Symptoms and Signs

• • Truncal obesity, hirsutism, moon facies, acne, buffalo hump, purple striae

  • Hypertension

  • Hyperglycemia

  • Weakness

  • Depression

  • Growth retardation or arrest in children

Laboratory Findings

• • Overnight, low-dose dexamethasone suppression test and measurement of urinary free cortisol establishes diagnosis

  • -No suppression and elevated urinary cortisol suggest Cushing syndrome

  • Detection of elevated midnight cortisol level suggests Cushing syndrome (midnight plasma level or late-night salivary cortisol sampling)

  • Once Cushing syndrome established, measure plasma ACTH level

  • -A repeatedly normal or elevated ACTH level suggests pituitary adenoma or ectopic ACTH secretion

    -Suppressed ACTH is diagnostic of hyperadrenocorticism due to primary adrenal disease

  • If ACTH-dependent Cushing disease and no clear pituitary lesion on MRI, may proceed to petrosal sinus sampling with corticotropin-releasing hormone (CRH) stimulation: a central to peripheral ACTH gradient suggests Cushing disease, while no gradient suggests ectopic ACTH secretion

Imaging Findings

• • MRI finding of pituitary lesion suggests Cushing disease

  • Cushing syndrome caused by primary adrenal diseases: Thin-section CT scan or MRI can detect virtually all adrenal tumors and hyperplasia

• • Rare forms of ACTH-independent Cushing syndrome include macronodular hyperplasia

  • Pigmented micronodular hyperplasia is associated with the syndrome of Carney complex (also includes cardiac myxomas and lentigines)

  • Rarely, ectopic adrenal tissue can be the source for excess cortisol secretion; most common location is along the abdominal aorta

  • Ectopic ACTH syndrome usually caused by small-cell lung cancers or carcinoids but can result from tumors of the pancreas, thyroid, thymus, prostate, esophagus, colon, ovaries, pheochromocytoma, and malignant melanoma

  • False-positive dexamethasone suppression tests seen in patients with depression, physiologic stress, marked obesity, renal failure, or taking drugs that accelerate dexamethasone metabolism (phenytoin, rifampin, phenobarbital); estrogens increase cortisol binding globulins and elevate total plasma cortisol concentrations

• • Complete history and physical exam

  • Overnight, low-dose dexamethasone suppression test

  • 24-hour urinary cortisol measurement

  • Plasma ACTH level

  • Directed imaging including pituitary MRI or abdominal CT or MRI

  • Potential role for petrosal sinus sampling to delineate nonvisualized pituitary source for excess ACTH

• • Resection is best treatment for cortisol-producing adrenal tumors or ACTH-producing tumors

  • Pituitary irradiation may be necessary if pituitary surgery fails

  • Medical treatment may be indicated to control hypercortisolism, or when patients not cured by resection or when complete resection is impossible