To the Editor: Cushing’s syndrome secondary to olfactory neuroblastoma is rare (1). We report a case of psychiatric manifestations caused by Cushing’s syndrome secondary to ectopic ACTH secretion from an olfactory neuroblastoma. This is the first report of which we are aware of psychiatric manifestations caused by Cushing’s syndrome that have been controlled for more than 1 year by metyrapone, an 11β-hydroxylase inhibitor. In addition, abnormal regulation of ACTH secretion was suspected; this abnormality may have brought about the dramatic effectiveness of metyrapone.
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.
After administration of metyrapone, the patient’s Cushing’s syndrome and psychiatric manifestations immediately resolved; his cortisol levels and ACTH levels immediately became normal. Metyrapone can inhibit production of cortisol but not ACTH directly. Therefore, in this case, there may have been positive feedback regulation between cortisol and ACTH in the tumor. After reduction of the cortisol level with metyrapone, the effect of the positive feedback regulation of cortisol on ACTH secretion might have decreased. In this case, decadrone, a glucocorticoid used with chemotherapy, may have triggered ACTH secretion by means of positive feedback regulation. Physicians should be aware that the potential abnormal regulation of cortisol secretion in a tumor can cause psychiatric manifestations.