Clinical presentation, diagnosis, and treatment of Cushingʼs syndrome

Abstract

Excess endogenous glucocorticoid production, whether corticotropin-dependent or -independent, results in the classic clinical and biochemical picture of Cushing's syndrome. The diagnosis requires demonstration of an increased cortisol secretion rate, but in mild cases, distinction from the hypercortisolism of pseudo-Cushing states may prove difficult. A dexamethasone or ovine corticotropin-releasing hormone test or close monitoring of the patient for a few months may be helpful. Most cases are diagnosed using: corticotropin-releasing hormone—stimulated plasma corticotropin level measurements and adrenal imaging procedures, A discrete pituitary lesion on imaging and a standard ovine corticotropin-releasing hormone test with results consistent with such a lesion are sufficient to proceed to transsphenoidal surgery. If no visible pituitary lesion is present, or if the ovine corticotropin-releasing hormone test is equivocal, bilateral simultaneous inferior petrosal sinus sampling with ovine corticotropin-releasing hormone administration is necessary to distinguish between a pituitary and an ectopic source. Surgical ablation is the treatment of choice for all types of Cushing's syndrome. In cases in which transsphenoidal surgery fails or in which the disease recurs, repeat transsphenoidal surgery and radiation therapy in association with mitotane treatment are reasonable alternatives. Bilateral adrenalectomy effectively cures hypercortisolism if resection of the corticotropin-secreting tumor is unsuccessful and radiation or medical therapy fails.