Successful Management of Ectopic Adrenocorticotropin-Secreting Thymic Carcinoid With Mitotane: A New Look at an Old Drug

Ectopic adrenocorticotropin syndrome (EAS) is usually associated with severe multiple complications and high mortality. Several adrenal steroidogenesis inhibitors can be used to control hypercortisolism when curative surgery is not feasible, but with different availability worldwide. It was long considered that mitotane (MTT) was not suitable for severe Cushing syndrome (CS) due to its delayed onset of action. We present a case of a 17-year-old girl with rapid-onset CS and an extremely high 24-hour urinary free cortisol (UFC) level (>300 times the upper limit of normal). An anterior mediastinal nodule with contrast enhancement was identified in computed tomography, with positive ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) positron emission tomography with computed tomography (PET/CT) uptake (maximum standardized uptake value = 10.1), suggestive of a thymic neuroendocrine tumor as the most likely cause of EAS. Preoperative MTT monotherapy titrated to 2 g/day reduced UFC by 85% within 13 days without adverse effects, stabilized severe neuropsychiatric disturbances and opportunistic infections, thus enabling successful thymectomy. The tumor turned out to be an adrenocorticotropin-secreting thymic typical carcinoid. Other EAS cases treated with MTT reported in the literature were reviewed, and the time needed to control hypercortisolism using MTT was shorter than previously reported. Instead of an "add-on drug," we should reconsider the role of MTT in the treatment of severe hypercortisolism in EAS.