J. Endocrinol. Invest. 30: 776-779, 2007 776 Key-words: Cushing’s syndrome, hypercortisolism, psychotic disorders, etomidate, mifepristone. Correspondence: Y.M. Bilgin, MD, Department of Internal Medicine, IJssel- land hospital, PO Box 690, 2900 AR Capelle aan den Ijssel, The Netherlands. E-mail: bilginyavuz@hotmail.com Accepted November 2, 2006. CASE REPORT Treatment of severe psychosis due to ectopic Cushing’s syndrome Y.M. Bilgin 1 , H.E. van der Wiel 1 , H.R.A. Fischer 1 , and W.W. De Herder 2 1 Department of Internal Medicine, IJsselland Hospital, Capelle aan den IJssel; 2 Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands ABSTRACT. Severe psychosis in patients with Cush- ing’s syndrome is rare and generally difficult to treat. We report a 46-yr-old woman suffering from Cushing’s syndrome caused by an inoperable ACTH- producing lung carcinoma. She was initially treated with chemotherapy and radiotherapy. Six months later she presented with severe psychosis. Labora- tory findings revealed a severe hypokaliemia and metabolic alkalosis, which was caused by extremely high serum ACTH (788 ng/l) and cortisol (4.2 mu- mol/l). She was unresponsive to treatment with con- ventional antipsychotic drugs; she was therefore sedated and intubated. Treatment was started iv with etomidate, which blocks the cortisol synthesis, and orally by nasogastric tube with mifepristone, which competes with cortisol for binding to their receptors. To counteract adrenal insufficiency, she received corticosteroids. After 5 days there was a normalization of the ACTH, cortisol levels, and the metabolic disorders. After discontinuing etomidate she was extubated; there were no signs of psycho- sis observed. Computed tomography (CT) scan of the brain showed no metastasis, however CT scan of the abdomen showed liver metastasis and bilat- eral adrenal enlargement. Unfortunately, the clini- cal situation worsened and the patient died due to progression of the metastasis. This case report demonstrates the efficacy of a treatment of mife- pristone with etomidate in a patient with an ectopic ACTH-producing Cushing’s syndrome. (J. Endocrinol. Invest. 30: 776-779, 2007) © 2007, Editrice Kurtis INTRODUCTION Psychiatric disturbances in patients with Cushing’s syndrome have frequently been observed. Most of the patients suffer from depression; severe psychosis in patients with Cushing’s syndrome is very rare (1). Psychosis in Cushing’s syndrome is generally diffi- cult to treat and in most cases there is little or no response to antipsychotic drugs. Mifepristone (RU 486) is an antiprogestin, which at higher dosages competes with glucocorticoids for binding to their receptor. Oral mifepristone has been successfully used for the treatment of acute psychosis in patients with Cushing’s syn- drome (2-4). Etomidate, a substituted imidazole, is a hypnotic drug, which blocks the enzyme 11- -hydroxylase, that catalyses the production of cortisol from 11- deoxycortisol. It lowers serum cortisol levels within 10-12 h. It has been administered in low doses iv to hospitalized patients with Cushing’s syndrome who cannot be treated with oral medication (5, 6). Here we report the combined use of mifepristone and etomidate in a patient with severe psychosis caused by an ectopic ACTH-producing lung carci- noma and Cushing’s syndrome. CASE REPORT A 46-yr-old woman was presented to our hospital with severe psychosis. One year before admission she had been diagnosed with Cushing’s syndrome caused by an inoperable ectopic ACTH-producing small cell carcinoma of the lung. She had been treated with 3 cycles of chemotherapy (carboplatin and paclitaxel) and external radiotherapy on the lung tumor (15 x 3 Gy). After this therapy, there was no further tumor regression and there were no signs of metastasis.