Neuroendocrine ACTH-producing tumor of the thymus - Experience with 12 patients over 25 years

Context: ACTH-producing neuroendocrine tumor (NET) of the thymus is a rare cause of Cushing's syndrome (CS). The literature consists mainly of isolated case reports. Patients: We studied 12 cases (eight males and four females) diagnosed between 1986 and 2010 with CS and thymic NET who underwent surgical resection. Main Outcome Measures: We measured time from onset of CS to diagnosis of thymic NET, tumor size, histological grade, time to recurrence, and survival and performed a meta-analysis of other published cases of CS associated with thymic NET. Results: Eleven of 12 patients presented with classic features of CS at a median age of 21 yr (range, 7-51). Four were children. The 24-h urine free cortisol was greater than 16-fold of normal, and biochemical testing was consistent with ectopic ACTH production in all 11. Another patient presenting with pulmonary embolus had a thymic mass and was later diagnosed with CS. All patients underwent thymectomy, and nine of 10 tumors exhibited positive ACTH immunochemistry. Median tumor diameter was 5 cm (frange, 1-11.5). Six patients recurred 20-28 months after surgery with metastases to mediastinal lymph nodes (n = 5), bone (n = 5), liver (n = 1), parotid gland (n = 1), and breast (n = 1). Four of five patients treated with radiation therapy also received chemotherapy. All recurrent patients received ketoconazole; four later underwent bilateral adrenalectomy. Six recurrent patients died 22-90 months (median, 57) after thymectomy. At last review, six patients were alive 14-90 months (median, 49) after thymectomy. These data are similar to those from the meta-analysis. Conclusions: Thymic ACTH-producing NET is an aggressive disease that should be considered in CS with ectopic ACTH secretion, particularly in younger patients.