Cushing Disease

Cushing Disease results from ACTH overproduction by a pituitary adenoma, stimulating excessive cortisol synthesis by the adrenal glands. Excess cortisol causes multiple systemic effects through glucocorticoid receptor activation. Characteristic appearance results from central fat redistribution with abdominal and dorsocervical obesity, supraclavicular fat pads ('buffalo hump'), and facial plethora ('moon facies'). Cutaneous changes include purple stretch marks, thin fragile skin with easy bruising, and hyperpigmentation. Metabolic complications include insulin resistance, type 2 diabetes (10-30% of patients), dyslipidemia, and growth impairment in children. Cardiovascular complications are severe, with hypertension occurring in 80% and representing a major source of morbidity. Osteoporosis develops in 50% due to accelerated bone loss. Psychiatric manifestations are prominent, with major depression occurring in 40-50%, and psychosis, anxiety, and cognitive impairment common. Immunosuppression increases infection risk. Diagnosis requires confirmation of hypercortisolism (24-hour urine cortisol, late-night salivary cortisol) and demonstration of ACTH source through inferior petrosal sinus sampling and pituitary imaging.