Adrenal Hyperfunction - Cushing Disease

Adrenal Hyperfunction - Cushing Disease

 

Clinical Hyperfunction

Adrenal hyperfunction (Cushing disease) is manifested as excess cortisol secretion by the adrenal gland.

Epidemiology

  • Incidence – 10/1,000,000
  • Age – uncommon in children; peak age 20-60 years
  • Gender – F:M; 4-6:1

Etiology

  • Endogenous
    • Pituitary
      • Hyperplasia
      • Adenoma
    • Adrenal
      • Adenoma
      • Carcinoma
    • Ectopic production of ACTH
      • Tumors (carcinoid, small cell lung cancer)
  • Exogenous
    • Glucocorticoid administration

Pathophysiology

  • Corticotropin-releasing hormone (CRH) in the hypothalamus stimulates release of ACTH from the pituitary gland
  • ACTH acts on the adrenal glands to produce cortisol
  • Most cases are caused by hypersecretion of pituitary ACTH or ectopic production of ACTH from non-pituitary source

Clinical Presentation

  • Amenorrhea
  • Centripetal obesity, moon facies, buffalo hump, hirsutism, striae
  • Emotional changes
  • Fatigue, weakness
  • Hypertension
  • Impaired glucose tolerance
  • Osteoporosis
  • Proximal myopathy

Diagnosis

  • Indications for testing – suspicion based on clinical presentation
  • Laboratory testing
    • Initial testing – 24-hour free urine cortisol or salivary cortisol between 11 and midnight; if positive, follow up with dexamethasone suppression testing
    • Differentiate etiology of Cushing disease – ACTH measurements
      • Inferior petrosal sinus ACTH
  • Imaging studies
    • CT/MRI to visualize adenomas/hyperplasia

Differential Diagnosis

  • Obesity
  • Type 2 diabetes
  • Depression
  • Polycystic ovarian disease

Treatment – Surgical Removal

  • Transsphenoidal removal of pituitary adenoma or carcinoma
  • Removal of adrenal adenoma or carcinoma
  • Removal of ectopic source of ACTH

Prognosis

  • Untreated Cushing disease is associated with excess morbidity/mortality secondary to cardiovascular disease
  • If tumor is benign and removed, may normalize mortality
  • Malignant tumors have poor prognosis

See Also