Ectopic Cushing Syndrome Secondary to Diffuse Idiopathic Neuroendocrine Cell Hyperplasia—A Report of 2 Cases

Abstract

Abstract Ectopic ACTH secretion (EAS) accounts for 10% to 20% of all Cushing syndrome cases. Diffuse intrapulmonary neuroendocrine cell hyperplasia (DIPNECH), a poorly understood lung disease, is characterized by abnormal proliferation of neuroendocrine cells in the bronchial mucosa. It is thought to be a precursor of pulmonary carcinoid and has been associated with EAS in a handful of cases. We present 2 patients with clinical, radiological, and pathological features of DIPNECH who presented with florid Cushing syndrome secondary to EAS evidenced by rapid onset of symptoms, elevated plasma ACTH, and cortisol levels, and failed high-dose dexamethasone suppression testing. Treatment of hypercortisolism included excision of the involved lung and medical therapy with steroidogenesis inhibitors. Despite the aggressive initial management, hypercortisolism persisted. This case series highlights the importance of considering DIPNECH as a cause for Cushing syndrome in the appropriate clinical scenario and underscores the likelihood that surgery may not be curative because of the diffuse nature of this disease. Given the high mortality associated with EAS, prompt medical therapy, appropriate prophylaxis, and bilateral adrenalectomy can be lifesaving measures when initial surgery fails.