Episodic Severe Ectopic Adrenocorticotropic Hormone Syndrome by Metastatic Appendiceal Neuroendocrine Tumor

Abstract

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.

Keywords: Cushing syndrome; Ectopic ACTH syndrome; Ectopic Cushing syndrome; appendiceal neuroendocrine tumor; severe hypercortisolism.

Figure 1.

Metastatic neuroendocrine tumor imaging. (A) Coronal image from initial computed tomography of the abdomen and pelvis demonstrating a 3-cm appendiceal mass (arrow). (B and C) Coronal mages from Gallium-68 (Ga-68) DOTA-Tyr3-octreotate (DOTATATE) positron emission tomography/CT (PET/CT) redemonstrating appendiceal mass (B, arrow) and hepatic mass (C, arrow).

Figure 2.

Histopathologic and immunohistochemical features of metastatic neuroendocrine tumor. Metastatic neuroendocrine tumor showed tumor cells with round or oval nuclei with salt and pepper chromatin and moderate eosinophilic granular cytoplasm arranged in nests, tubules and trabecular patterns (A), positive for synaptophysin (B) and chromogranin (C), and focally positive for ACTH (D).

Figure 3.

Episodic severe cortisol secretion demonstrated by serial laboratory measurements prior to bilateral adrenalectomy. ACTH (blue dashed line), serum cortisol (black dashed line), and 24-hour urine free cortisol (UFC) (red solid line) on initial presentation and before bilateral adrenalectomy. The peaks and troughs demonstrate episodic nature of cortisol production in this case.