SAT-041 - A Rare Cause of Refractory Hypokalemia: Ectopic ACTH Syndrome Diagnosed in A Community Hospital

Background
Ectopic adrenocorticotropic hormone (ACTH) syndrome (EAS), also known as ectopic Cushing syndrome, is a rare cause of ACTH-dependent hypercortisolism resulting from non-pituitary tumors. It is associated with severe metabolic abnormalities and significant morbidity. Ectopic ACTH accounts for approximately 5–10% of Cushing syndrome cases and often presents diagnostic challenges, particularly in community hospital settings with limited access to specialized endocrine testing.

Case Presentation
A 64-year-old woman with a significant smoking history and chronic obstructive pulmonary disease presented with altered mental status, generalized weakness, and unintentional weight loss. Laboratory evaluation revealed severe hypokalemia (2.4 mmol/L), leukocytosis (WBC 12.5 ×10⁹/L), anemia (hemoglobin 8.9 g/dL), thrombocytopenia (platelets 121 ×10⁹/L), and preserved renal function. Chest CT demonstrated a right perihilar mass with extensive mediastinal and right supraclavicular lymphadenopathy, concerning for primary lung malignancy. Additional imaging showed metastatic disease involving the thoracic spine and pancreatic tail.

Given refractory hypokalemia despite aggressive replacement, along with new-onset hyperglycemia and hypertension, endocrine evaluation was pursued. Morning serum cortisol was markedly elevated at 107.0 µg/dL. Aldosterone was suppressed ( < 1 ng/dL) with low-normal plasma renin activity (0.83 ng/mL/hr). A 1-mg overnight dexamethasone suppression test showed no suppression (cortisol 95.6 µg/dL). Twenty-four-hour urinary free cortisol was markedly elevated at 4,357.2 µg/L. Plasma ACTH was elevated at 478 pg/mL, consistent with ACTH-dependent Cushing syndrome. An 8-mg dexamethasone suppression test again demonstrated no suppression. Pituitary MRI revealed no adenoma. Inferior petrosal sinus sampling was not performed due to limited availability.

Based on clinical findings, biochemical data, and imaging, a diagnosis of ectopic ACTH syndrome, likely secondary to lung malignancy, was made. Given advanced metastatic disease, the patient and family elected palliative-focused care. Ketoconazole was initiated, resulting in symptomatic improvement and a decline in serum cortisol to 19 µg/dL.

Conclusion
Ectopic ACTH syndrome should be considered in patients with refractory hypokalemia and severe hypercortisolism. This case highlights the importance of integrating biochemical evaluation and imaging to establish the diagnosis in community hospital settings. Early medical therapy with steroidogenesis inhibitors can provide meaningful biochemical and symptomatic benefit when surgical intervention is not pursued.

*Unless otherwise noted, all abstracts presented at ENDO must not be released to the press or the public until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.*