Hypokalemic metabolic alkalosis as a clinical clue to ectopic ACTH syndrome: two cases of neuroendocrine carcinoma.

Objective. Ectopic adrenocorticotropic hormone (ACTH) syndrome (EAS) is a rare, but potentially life-threatening cause of Cushing's syndrome. Its clinical recognition may be delayed, especially when classical features of hypercortisolism are absent. We present two cases, in which hypokalemic metabolic alkalosis was the initial and main clinical clue leading to the diagnosis of neuroendocrine carcinoma with ectopic ACTH production. Case 1. The first case was a 71-year-old woman admitted with progressive weakness, gait disturbance, and uncontrolled hypertension. Laboratory tests revealed severe hypokalemia and metabolic alkalosis. Endocrine evaluation showed markedly elevated urinary free cortisol and plasma ACTH, with absent suppression on low-dose dexamethasone testing. Colonoscopy for anemia revealed a rectal mass and histopathology confirmed poorly differentiated neuroendocrine carcinoma. Imaging demonstrated widespread metastases. Despite supportive treatment, she died of multi-organ failure during hospitalization. Case 2. The second case was a 67-year-old woman presenting with fatigue, weakness, and weight loss. Laboratory findings included hypokalemia, metabolic alkalosis, renal dysfunction, and elevated liver enzymes. Hormonal studies again confirmed ACTH-dependent Cushing's syndrome without suppression on dexamethasone testing. Imaging revealed a right hilar lung mass and bronchoscopy with biopsy confirmed small-cell neuroendocrine carcinoma. PET-CT showed disseminated metastases. Although chemotherapy was initiated, she developed rapid progression and died shortly thereafter. Conclusion. These cases highlight that severe hypokalemic metabolic alkalosis may represent the primary manifestation of ectopic ACTH syndrome even in the absence of overt Cushingoid features. Recognition of this biochemical pattern should prompt consideration of neuroendocrine tumors allowing earlier diagnosis and timely therapeutic intervention in this aggressive condition.