SAT-037 - Rare Source, Severe Disease: Ectopic ACTH Syndrome from Metastatic Small Intestinal Neuroendocrine Tumor

INTRODUCTION
Ectopic adrenocorticotropic hormone (ACTH) secretion accounts for 10–20% of cases of endogenous Cushing syndrome, most commonly arising from bronchial carcinoids and small-cell lung carcinoma. Ectopic Cushing syndrome (ECS) due to small intestinal neuroendocrine tumors (NETs) is exceedingly rare and poses significant diagnostic and management challenges.
CASE DESCRIPTION
A 69-year-old male with a history of small intestinal carcinoid tumor presented with severe, refractory hyperglycemia, hypokalemia, metabolic alkalosis, and fatigue.

Biochemical evaluation demonstrated elevated serum cortisol and ACTH levels with failure to suppress on low-dose dexamethasone testing, consistent with ACTH-dependent hypercortisolism. Cross-sectional imaging revealed multiple hypoenhancing hepatic lesions suspicious for metastases. Liver biopsy confirmed a well-differentiated, chromogranin-positive neuroendocrine tumor.

Given the clinical, biochemical, and radiologic findings, ectopic ACTH syndrome secondary to metastatic NET was diagnosed. The patient was initiated on ketoconazole with subsequent improvement in cortisol levels and correction of metabolic derangements.
DISCUSSION
ECS is an uncommon but severe form of Cushing syndrome often associated with rapid onset hypercortisolism, profound hypokalemia, and increased morbidity. Localization of the ACTH source remains challenging, particularly in patients with known malignancy or incidental pituitary findings.

Current guidelines recommend a stepwise approach incorporating biochemical confirmation, imaging, and selective use of inferior petrosal sinus sampling when needed. Small intestinal NETs represent a rare source of ectopic ACTH production, with limited cases reported in the literature.

This case highlights the importance of considering ectopic ACTH production even in patients with known neuroendocrine tumors, as hormonal transformation may occur during disease progression.

Management includes definitive surgical resection when feasible. However, in metastatic or unresectable disease, medical therapy with steroidogenesis inhibitors (e.g., ketoconazole, metyrapone) is essential to control hypercortisolism and reduce associated complications.
CONCLUSION
Ectopic ACTH syndrome from small intestinal neuroendocrine tumors is rare but should be considered in patients with severe, rapidly progressive hypercortisolism and metabolic abnormalities. Early recognition, appropriate localization, and prompt initiation of medical therapy are critical to improving outcomes.

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