Episodic Severe Ectopic Adrenocorticotropic Hormone Syndrome by Metastatic Appendiceal Neuroendocrine Tumor

Episodic severe Cushing syndrome resulting from ectopic ACTH secretion (EAS) from appendiceal neuroendocrine tumor (NET) is extremely rare. Here, we describe a case of a 24-year-old woman with episodic severe EAS resulting from appendiceal NET with extensive metastatic disease. The patient presented with rapid weight gain, violaceous striae, fatigue, edema, and anxiety. Biochemical evaluation showed markedly elevated 24-hour urinary free cortisol greater than 10-fold above the upper limit of normal, and widely fluctuating peaks and troughs of serum cortisol and ACTH concentrations indicating episodic severe EAS. Surgery for primary malignancy was initially deferred because of the high risk of perioperative complications related to severe hypercortisolism. She underwent bilateral adrenalectomy as first-line definitive treatment for severe EAS. Four months after adrenalectomy, she underwent cytoreductive surgery for primary metastatic appendiceal NET. Subsequent peptide receptor radionuclide therapy and monthly lanreotide injections rendered her disease stable. Three years after the initial presentation, she continued to undergo active surveillance with maintenance lanreotide for residual but stable metastatic appendiceal neuroendocrine tumor. This case of a rare metastatic appendiceal NET with EAS demonstrates the importance of individualized management and highlights the need for consideration of prompt bilateral adrenalectomy for patients with severe Cushing syndrome.