Cushing’s disease
Overview
Cushing’s disease is the specific cause of Cushing’s syndrome due to an ACTH‑secreting pituitary adenoma. Differentiate it from:
- Cushing’s syndrome: any clinical state of cortisol excess (endogenous or exogenous).
- Exogenous (iatrogenic) Cushingoid state: the commonest cause of cortisol excess-always check medication history (systemic, topical, inhaled, injected).
Excess pituitary ACTH drives adrenal hypersecretion of cortisol, producing characteristic metabolic and physical features and, when tumours are large, local mass effects.
Pathophysiology and endocrine physiology
- Normal cortisol has a marked diurnal rhythm (highest in the morning, lowest around midnight).
- In Cushing’s disease the circadian rhythm is lost and cortisol remains inappropriately high across 24 hours; morning values can be normal while late‑night levels are elevated.
- Pituitary corticotroph adenomas secrete ACTH autonomously, so plasma ACTH is typically elevated or inappropriately normal for the cortisol level.
Chronic cortisol excess causes:
- Metabolic effects: insulin resistance, glucose intolerance or diabetes, hypertension.
- Catabolic effects: proximal myopathy, skin thinning, easy bruising, purple abdominal striae, osteoporosis.
- Mineralocorticoid‑like effects in some patients: hypokalaemia.
- Immunosuppression and neuropsychiatric effects.