When Potassium Won't Budge: Unraveling Hypertension and Ectopic ACTH Syndrome in a Case of Severe Hypercortisolism

Introduction: Refractory hypokalemia is a rare but clinically significant paraneoplastic manifestation of small cell lung cancer (SCLC), seen in approximately 1–5% of cases. It is often caused by ectopic adrenocorticotropic hormone (ACTH) production, leading to excess cortisol secretion with mineralocorticoid-like effects. The pathophysiology involves renal potassium wasting, sodium retention, and metabolic alkalosis. These disturbances often precede the classic features of Cushing’s syndrome and can pose diagnostic and therapeutic challenges, particularly for nephrologists. Case Description: A 59-year-old woman with a new diagnosis of metastatic SCLC (10 days prior) presented with progressive muscle weakness, fatigue, and hypertension refractory to multiple antihypertensive agents. She also reported polydipsia and polyuria. Physical exam showed persistent hypertension but lacked cushingoid features such as moon facies, central obesity, or striae. Labs revealed persistent hypokalemia despite aggressive replacement and elevated serum ACTH and cortisol levels. Discussion: SCLC may secrete ectopic ACTH, stimulating adrenal hyperplasia and cortisol excess. The resulting hypercortisolism can overwhelm 11β-hydroxysteroid dehydrogenase type 2, allowing cortisol to activate renal mineralocorticoid receptors. This leads to sodium retention, potassium loss, and metabolic alkalosis. Clinically, patients present with resistant hypertension and hypokalemia, often without classic Cushing’s signs. These findings may precede or obscure the diagnosis of malignancy and are frequently resistant to standard potassium repletion. Management typically requires high-dose potassium and mineralocorticoid receptor antagonists. The absence of overt Cushingoid features can delay recognition, highlighting the need to consider ectopic ACTH syndrome in patients with unexplained hypokalemia and hypertension, especially in the context of known or suspected malignancy.