Metyrapone for Cushing’s Syndrome

Mr. A was a 33-year-old man who underwent resection of a nasal olfactory neuroblastoma at 26 years of age. Seven years later, metastases were diagnosed in the retropharyngeal lymph nodes, and chemotherapy, consisting of cisplatin and etoposide plus decadrone, was administered. After that, Mr. A experienced numbness in his lower extremities, dysgeusia, adynamia, stomatitis, facial and extremity edema, diarrhea, and thrombocytopenia; unexplained hypokalemia was found. These symptoms were believed to be adverse effects from chemotherapy. Mr. A then developed anxiety, irritability, insomnia, and psychomotor excitement and was referred to the psychiatry division.

Mr. A gradually began to exhibit a depressed mood and suicidal ideation. At first these symptoms were diagnosed as an adjustment disorder with mixed anxiety and depressed mood. Psychotropic medication was effective in treating the psychomotor excitement. After the completion of chemotherapy, however, the anxiety, irritability, insomnia, and depressed mood persisted. Because of these long-lasting psychiatric manifestations and the hypokalemia, Mr. A was tested for a hormonal abnormality and was found to have elevated plasma levels of ACTH (837 pg/ml; normal range=9–520 pg/ml) and cortisol (103 μg/dl; normal range=5–15 μg/dl). In addition, an abdominal magnetic resonance imaging (MRI) examination revealed bilateral adrenal hypertrophy; an MRI of the head was negative for pituitary tumors or hypertrophy. Cushing’s syndrome secondary to an ectopic ACTH-secreting tumor was diagnosed, and metyrapone treatment was begun.

Mr. A’s cortisol level became normal (7.4 μg/dl), and his anxiety, irritability, insomnia, and depressed mood improved 6 days later. His Cushing’s syndrome and psychiatric manifestations have been controlled with metyrapone, 750 mg/day, for more than 24 months. His cortisol level has been maintained within the normal range, and his ACTH level has been stabilized around 200 pg/ml for more than a year.