What is the most common cause of Cushing syndrome?

• A. Adrenal adenoma
• B. Ectopic ACTH production
• C. Pituitary ACTH deficiency
• D. Exogenous corticosteroid use

Answer: (D)

Exogenous corticosteroid use is the most common cause of Cushing syndrome. When systemic glucocorticoids are taken for conditions like asthma, autoimmune disease, or after transplantation, they raise circulating cortisol-like activity throughout the body. This iatrogenic excess produces the same clinical features of Cushing syndrome—weight gain, moon face, dorsocervical fat pad, proximal muscle weakness, glucose intolerance, and hypertension—by circulating high levels of corticosteroids.

The body’s negative feedback lowers ACTH in response to these external steroids, which can lead to adrenal atrophy and reduced endogenous cortisol production, but the overall glucocorticoid effect remains elevated due to the drugs themselves.

Other causes exist but are less common. Adrenal tumors can autonomously overproduce cortisol, and ACTH-dependent endogenous causes include a pituitary adenoma (Cushing disease) or ectopic ACTH-producing tumors. Pituitary ACTH deficiency, on the other hand, would not cause Cushing syndrome; it would lead to low cortisol levels.