Clinical meaning
Cushing syndrome is the clinical condition resulting from prolonged exposure to excessive glucocorticoids, either from endogenous overproduction or exogenous administration. It is important to distinguish Cushing syndrome (the clinical state from any cause) from Cushing disease (specifically caused by an ACTH-secreting pituitary adenoma, accounting for 70% of endogenous cases).
The most common cause of Cushing syndrome is iatrogenic - prolonged administration of exogenous glucocorticoids (prednisone, dexamethasone, hydrocortisone) for conditions such as autoimmune diseases, asthma, organ transplant rejection, and inflammatory conditions. Even inhaled and topical steroids at high doses can cause cushingoid features.
Endogenous causes are categorised as ACTH-dependent or ACTH-independent. ACTH-dependent causes (80% of endogenous cases) include Cushing disease (pituitary corticotroph adenoma secreting excess ACTH, 70%) and ectopic ACTH syndrome (ACTH secretion from non-pituitary tumours - small cell lung cancer, bronchial carcinoids, pancreatic neuroendocrine tumours, 10%). ACTH-independent causes (20%) include adrenal adenoma, adrenal carcinoma, and bilateral adrenal hyperplasia.
Excessive cortisol produces widespread metabolic and physiologic effects. Glucocorticoid excess promotes hepatic gluconeogenesis and insulin resistance, causing hyperglycemia and potential steroid-induced diabetes. It enhances lipogenesis in central and facial fat deposits while promoting lipolysis in the extremities, creating the characteristic central obesity, moon facies, and buffalo hump (dorsocervical fat pad) with thin extremities.
Protein catabolism causes proximal muscle wasting (difficulty rising from a chair, climbing stairs), skin thinning with easy bruising, poor wound healing, and wide purple striae (distinct from the narrow white-pink striae of pregnancy or growth). The purple colour results from the thin dermis allowing visualisation of the underlying red-blue vasculature. Bone protein matrix breakdown leads to osteoporosis with pathologic fractures and avascular necrosis.