SUN-397 A Rare Case of Ectopic Adrenocorticotropic Hormone (ACTH) Syndrome Due to Thymic Large Cell Neuroendocrine Carcinoma Presenting as Severe Hypokalemia in a Taiwanese Man

Abstract

Background Ectopic ACTH syndrome (EAS) represented 5% of Cushing syndrome. EAS is rapid onset, severe, associated with hypercortisolism related life-threatening infections and hypokalemia. In 60% of cases, the tumor is located in intrathoracic organ (lung, bronchus and thymus). Large cell neuroendocrine tumor of thymus secreting ACTH is a high grade, aggressive, poor prognosis and only few case reports in literature. Here we report a case of thymic LCNEC related EAS, which presented as severe hypokalemia, metabolic alkalosis and muscle weakness. Clinical Case A 71-year-old man presented with 12-kg weight loss, progressive generalized weakness and bilateral legs edema for two months.He has medical histories of hypertension and diabetes mellitus. Physical examination revealed generalized weakness without Cushingoid appearance. Laboratory examination showed metabolic alkalosis and severe hypokalemia (1.7 mmol/L, range 3.4-4.7).Hypokalemia work-up showed high morning ACTH 497 pg/mL (normal <46.0), cortisol 87.8 μg/dL (range 3.7-19.4), and normal limits of other pituitary hormones. Cushing syndrome survey showed lack of ACTH/cortisol circadian rhythm, markedly increased 24h urinary free cortisol excretion on two consecutive days ( 21429, 17061 μg). Low-dose and high-dose dexamethasone suppression tests showed non-suppressible. Ovine corticotrophin-releasing hormone stimulation test and desmopressin (DDAVP) test showed ectopic ACTH source. Pituitary MRI revealed negative findings. Bilateral inferior petrosal sinus sampling showed no central-to-peripheral ACTH gradient. Ectopic ACTH syndrome was impressed. Etomidate continuous infusion was prescribed.Fournier gangrene of left scrotum occurred during hospitalization and antibiotic and surgical treatment were given. Chest CT scan revealed tiny lobulated nodule in left lower lung field and soft tissue nodule in prevascular of mediastium. In-111 Octreoscan revealed several nodular lesions with increased In-111 uptake in the paraortic and prevascular region considering neuroendocrine tumor. Anterior mediastinal tumor excision was performed and histopathological report showed large cell neuroendocrine carcinoma of thymus with mitotic count 13/10 HPF and positive immunohistochemical stain for synaptophysin, chromogranin, DD-56, SSTR2 and ACTH. Sandostain LAR injection was administered afterward. Unfortunately, tumor progression with hypercortisolemia occurred after 6 months . External radiation and systemic chemotherapy were performed later. Clinical Lessons Although rare, Cushing syndrome must be considered in differential diagnosis of hypokalemia like our case, a challenging case of EAS. Early diagnosis and treatment was important to avoid life-threatening infections and metabolic complications. Moreover recurrence free survival with Sandostain LAR alone was only 6 months for LCNEC.