Metyrapone in the Management of Severe Hypercortisolism Secondary to Ectopic Cushing's Syndrome

Ectopic Cushing's syndrome (ECS) is a rare but important cause of ACTH-dependent Cushing's syndrome. Metyrapone, a steroidogenesis inhibitor targeting 11-β hydroxylase, has shown effectiveness in controlling hypercortisolism. However, little is known about the practical aspects of its initiation, use, and effectiveness in ECS. We present three cases of severe hypercortisolism secondary to ECS managed with metyrapone and report our experience. Case 1: a 56-year-old male with high-grade neuroendocrine carcinoma. Case 2: a 67-year-old man with a history of stage IIB non-small cell lung cancer (NSCLC) with metastatic neuroendocrine carcinoma. Case 3: a 64-year-old man with metastatic prostate cancer. Biochemical control was achieved with rapid titration of low doses of daily metyrapone in all three cases. Based on our experience, we recommend an initial dose of 1000-1500 mg of metyrapone daily, in divided doses, with physiologic glucocorticoid replacement to mitigate the risk of adrenal insufficiency. Despite improvements in cortisol levels and stabilization of metabolic derangements, all three patients ultimately transitioned to comfort-focused care. Given the rarity, heterogeneity, and aggressiveness of this condition, rapid diagnosis and standardized pharmacologic approach are difficult to achieve. More data are needed to guide optimal therapy selection, dosing, and titration in ECS.