Cushing Syndrome
A hormonal disorder caused by prolonged exposure to inappropriately high levels of cortisol.
Emergency Management: Nelsons syndrome post-bilateral adrenalectomy (rapidly expanding pituitary macroadenoma with hyperpigmentation). Acute adrenal crisis if steroids are abruptly stopped.
Cushing syndrome is a clinical condition resulting from chronic exposure to excessive circulating levels of glucocorticoids. It primarily affects metabolic, cardiovascular, and musculoskeletal systems due to prolonged hypercortisolism. The most common cause is exogenous administration of synthetic corticosteroids.
Detailed Overview
Endogenous hypercortisolism is classified as ACTH-dependent (e.g., Cushing disease from a pituitary adenoma, ectopic ACTH from small cell lung cancer) or ACTH-independent (e.g., adrenal adenoma/carcinoma). Chronic hypercortisolism leads to altered fat distribution, catabolism of protein in skin and muscle, and metabolic disturbances like impaired glucose tolerance. Early diagnosis is crucial to prevent complications such as severe hypertension, osteoporosis, and recurrent infections.
Epidemiology & Demographics
Incidence of endogenous Cushing syndrome is 2-3 per 1 million people annually. The median age of onset is 41.4 years. It is three times more common in females than in males. Cushing disease accounts for 70% of endogenous cases.
Etiological Mechanism
Exogenous etiology involves iatrogenic corticosteroid therapy. Endogenous causes include corticotroph pituitary adenomas (Cushing disease, 70%), ectopic ACTH secretion (10-15%, often bronchial carcinoids or small cell lung cancer), and primary adrenal tumors (15-20%, adrenal adenomas or carcinomas).
Primary Causes
Long-term prednisone use (e.g., for asthma or RA), pituitary microadenoma secreting ACTH, ectopic ACTH-producing tumors, macronodular or micronodular adrenal hyperplasia.
Excess cortisol binds to glucocorticoid receptors, upregulating gluconeogenesis and glycogenolysis, leading to hyperglycemia. It stimulates lipolysis centrally but promotes central adipogenesis. High cortisol exerts mineralocorticoid activity by overwhelming 11-beta-hydroxysteroid dehydrogenase type 2, causing renal sodium retention and potassium wasting. Protein catabolism leads to muscle wasting and thinning of the dermis. Furthermore, cortisol inhibits osteoblast function and decreases intestinal calcium absorption, driving osteoporosis.
Diagnostic Criteria & Guidelines
Requires at least two abnormal first-line tests: 1) 24-hour urine free cortisol (UFC) > normal range (usually >50 mcg/24h) for assay, 2) Late-night salivary cortisol (LNSC) > 145 ng/dL, or 3) 1-mg overnight dexamethasone suppression test (ODST) showing 8 AM serum cortisol > 1.8 mcg/dL (50 nmol/L).
For exogenous: gradual tapering of the offending glucocorticoid. For pituitary adenoma: Transsphenoidal selective adenomectomy. For adrenal adenoma: Unilateral laparoscopic adrenalectomy. For ectopic ACTH: Resection of the primary tumor.
Second-Line & Adjunctive Therapy
Medical therapy if surgery is contraindicated or fails: Ketoconazole 200 mg PO TID up to 1200 mg/day, Metyrapone 250 mg PO QID, or Mifepristone 300 mg PO daily for hyperglycemia. Pituitary irradiation (radiosurgery) for recurrent Cushing disease.
Surgical & Procedural Management
Transsphenoidal surgery (TSS) for Cushing disease (remission rate 70-90%). Bilateral adrenalectomy as definitive therapy for occult or unresectable ectopic ACTH or failed TSS, requiring lifelong glucocorticoid and mineralocorticoid replacement.
Patient Counseling & Advice
Warn patients of postoperative adrenal insufficiency symptoms (fatigue, nausea, hypotension). Remind them that physical changes (e.g., striae, body fat redistribution) may take 6-12 months to resolve after cure.
Follow-Up & Monitoring Schedule
Measure morning serum cortisol and ACTH on post-op days 1-3. Long-term monitoring: 24-hr UFC, LNSC, or 1-mg DST every 6-12 months. DEXA scan every 1-2 years.
Preventive Strategies
Strict indication and minimal effective dose/duration for exogenous corticosteroid prescriptions. Alternate-day dosing for chronic steroid requirement if possible.
Untreated endogenous Cushing syndrome has a 5-year mortality of 50%. With surgical cure, 10-year survival normalizes, but patients maintain higher cardiovascular risk profiles for years.