An aggressive Cushing's syndrome originating from a rare thymic neuroendocrine tumor, controlled successfully with fluconazole and octreotide therapy before surgery.

Abstract: Cushing's syndromes (CSs) due to the thymic neuroendocrine tumors are rarely seen. Here, a case of ectopic CS originating from an atypical neuroendocrine tumor has been presented. A 49-year-old woman was hospitalized with symptoms of fatigue, chest pressure, dyspnea, muscle weakness, and resistant hypertension. There was marked hyperpigmentation in the whole-body surface suggestive of adrenocorticotropic hormone (ACTH) excess and there were physical features of CS. There was deep hypokalemia. Basal hormone profile, dexamethasone suppression tests, midnight cortisol, and 24-hour urine cortisol levels were suggestive of ectopic CS. The pituitary magnetic resonance imaging revealed a 5 mm cystic lesion and the patient refused inferior petrosal sinus sampling. Thorax computerized tomography showed an anterior mediastinal mass. A fluorodeoxyglucose-positron emission tomography showed the same mediastinal lesion (suvmax: 11.4), and no other tumor focus was detected. There was an aggressive cortisol excess causing acute respiratory distress syndrome, making it difficult to perform the surgery. We immediately started fluconazole and octreotide therapy and were successful in lowering the cortisol level. Then a complete resection of the tumor had been able to be surgically performed and tumor cells showed strong cytoplasmic immunopositivity with ACTH. A definitive diagnosis of "ACTH secreting atypical thymic carcinoid tumor" was rendered based on the histopathological and immunohistochemical features. There was only surrounding vessel invasion, and no lymphoid or other organ metastases were detected. As there were surrounding vessel invasions, a two-cycle regimen cisplatin-etoposide chemotherapy and radiotherapy were employed. After surgical and medical therapy, the cortisol and ACTH levels turned to normal. The patient is in biochemical and clinical remission and has no tumor recurrence yet. Ectopic ACTH-producing thymic carcinoids are rare but life-threatening tumors because of the underlying malignancy and severe hypercortisolemia. It is important to consider this disease and perform appropriate treatment at the right time. Today, surgery is the standard therapeutic modality if it is possible to perform, but there is not a clear and constant recommendation for nonsurgical therapeutic modalities. Further studies are needed for the optimal treatment strategies.