Cushings

Cushing's syndrome is a collection of signs and symptoms caused by prolonged exposure to elevated levels of glucocorticoids, particularly cortisol. The condition can be endogenous, arising from the body's own overproduction of cortisol, or exogenous, resulting from prolonged use of glucocorticoid medications. Endogenous causes include pituitary ACTH overproduction (Cushing disease), cortisol-producing adrenal tumors, and ectopic ACTH production from non-pituitary tumors. Exogenous Cushing's is the most common overall cause.

The pathophysiology involves cortisol effects on fat distribution, protein metabolism, glucose regulation, and the vascular system. ACTH-dependent forms involve excess ACTH stimulating the adrenals, while ACTH-independent forms involve autonomous cortisol production by the adrenal gland. Distinguishing the cause relies on biochemical testing and imaging to locate the source of cortisol excess.

Common features include central obesity, moon facies, a dorsocervical fat pad, abdominal striae, proximal muscle weakness, hypertension, glucose intolerance or diabetes, osteoporosis, and mood or cognitive changes. Patients may also experience sleep disturbances, hirsutism in women, and easy bruising.

Diagnosis typically starts with screening tests such as 24-hour urinary free cortisol, late-night salivary cortisol, or an overnight dexamethasone suppression test. If cortisol excess is confirmed, measuring ACTH helps differentiate ACTH-dependent from ACTH-independent causes, followed by targeted imaging of the pituitary, adrenals, or other potential sources.

Treatment depends on the cause. Exogenous Cushing's requires tapering or discontinuing the offending medication when possible. Endogenous etiologies are managed with surgery (transsphenoidal surgery for Cushing disease; adrenalectomy for adrenal tumors), radiotherapy for certain pituitary cases, and medical therapies to reduce cortisol production or action. Ongoing management addresses complications, including osteoporosis, infections, and metabolic disorders, with regular follow-up.