La malattia di Cushing: Stato dell'arte

ACTH-secreting pituitary adenomas (Cushing's disease) are the most common cause of endogenous hypercortisolism (70% of cases). The tumors are usually microadenomas (90%), while macroadenomas or malignant lesions may rarely occur. The differentiation of an ACTH-secreting pituitary tumor from other causes of ACTH-dependent hypercortisolism is based on biochemical studies and imaging evaluation (MRI, CT, ¹¹¹In-octreotide scintigraphy). The inhibition of ACTH and cortisol levels after high-dose dexamethasone administration and the responsiveness to CRH and desmopressin stimulation tests are suggestive for Cushing's disease. High-resolution MRI scans of the pituitary at 1.5 T, after gadolinium enhancement, is more sensitive than CT in detecting corticotrophe adenomas, and is able to localize microadenomas in about two thirds of patients. Bilateral inferior petrosal sinus sampling for ACTH determination, before and after CRH or desmopressin stimulation, is a reliable means of demonstrating pituitary microadenomas, undetected by MRI or CT scans and is useful to localize the tumor within the pituitary gland. The treatment of choice for adult patients with Cushing's disease is transsphenoidal adenomectomy with a cure rate of 75-80% after the initial surgery. The incidence of recurrence after successful adenomectomy is about 12%. Pituitary irradiation is the most appropriate next choice for adult patients not cured by pituitary surgery, and the initial therapy in pediatric patients. In the last years, stereotactic radiotherapy with the Co gamma knife is available and seems to be more effective, with less long-term side effects, than conventional radiotherapy. Drug therapy with adrenal enzyme inhibitors and bilateral surgical adrenalectomy is useful in patients in whom all other therapies have failed.