Ectopic ACTH syndrome presenting as refractory hypokalemia in metastatic castration-resistant prostate cancer with neuroendocrine transformation

Ectopic adrenocorticotropic hormone (ACTH) syndrome resulting from neuroendocrine transformation of prostate adenocarcinoma may present with refractory hypokalemia as an initial manifestation. Because hypokalemia is often attributed to other more common aetiologies, the diagnosis is often overlooked, leading to delayed management. A 62-year-old man with metastatic castration-resistant prostate cancer (mCRPC) with neuroendocrine transformation presented with persistent hypokalemia. He later developed severe hypokalemia, metabolic alkalosis, and hypertension with disease progression. Endocrine workup revealed markedly elevated cortisol, no suppression on low dose dexamethasone testing, and elevated ACTH. Imaging showed no pituitary or adrenal lesions but demonstrated progression of metastatic disease. These findings supported ectopic ACTH secretion secondary to neuroendocrine transformation. Before initiation of the appropriate treatment, he developed supraventricular tachycardia, hypotension, pulmonary edema, and died. This case underscores the importance of considering paraneoplastic endocrine syndromes, such as ectopic ACTH secretion, in patients with malignancies and unexplained or refractory electrolyte disturbances—particularly in the context of neuroendocrine transformation.