A Storm of Cortisol: Ectopic ACTH-Induced Metabolic Chaos

Introduction: Ectopic ACTH syndrome results from production of ACTH from extra-pituitary sources and accounts for approximately 4-5% cases of Cushing’s Syndrome. We present a case of a 75 year old non diabetic man with known metastatic prostate adenocarcinoma who presented to the hospital with new hyperglycemia, hypertension, hypokalemia, and metabolic alkalosis. Case Description: The patient had a history of prostate adenocarcinoma that was responsive to androgen deprivation therapy and chemotherapy, but his course was complicated by a rapidly progressive neuroendocrine tumor (NET) transformation. Two months after the NET diagnosis, he presented to the hospital with generalized fatigue. Upon evaluation, he was hypertensive, hypervolemic, and denied vomiting. Labs revealed hypokalemia and metabolic alkalosis. Other initial labs are listed in Table 1. Given the constellation of clinical findings, further evaluation for mineralocorticoid excess was performed and yielded the following: low normal renin activity: 1.0 ng/ml/hr; aldosterone: 4.5 ng/dL. Morning cortisol, ACTH, and 24 hr urine free cortisol were significantly elevated at 67.5 μg /L, 448.0 pg/mL (6.2-63.3 pg/mL), and 3997.5 μg /day (< 60 μg/day), respectively. Treatment was initiated with potassium chloride supplementation and eplerenone leading to improvement in the metabolic alkalosis and hypokalemia. After treatment with etoposide and carboplatin for his NET, his potassium supplements were eventually stopped. Discussion: We present a case of ectopic ACTH-dependent Cushing’s syndrome (EAC) in the setting of a metastatic neuroendocrine tumor. The clinical presentation of EAC differs from non-ectopic forms of Cushing’s syndrome by the presence of hypokalemia in 80% of the cases compared to 20% which is related to the degree of hypercortisolism in EAC. Excess glucocorticoid can often induce hypertension, metabolic alkalosis and hypokalemia. These changes are driven by saturation of renal 11β-hydroxysteroid dehydrogenase’s ability to inactivate cortisol to cortisone. This oversaturation then activates mineralocorticoid receptors in the collecting ducts leading to sodium retention, potassium wasting, and bicarbonate reabsorption. Test results upon presentation - Tests Sodium Potassium Chloride Bicarbonate BUN Creatinine Albumin Glucose ABGs pH PaCO2 PaO2 aHCO3 Random urine chloride Random urine potassium Results (reference range) 136 meq/L (137-144 meq/L) 2.7 meq/L (3.6-5.1 meq/L) 90 meq/L (100-111 meq/L) 33 meq/L (23-32 meq/L) 19 mg/dL (8-24 mg/dL) 1.5 mg/dL (0.6-1.2 mg/dL) 3.2 g/dL (3.8-5.3 g/dL) 448 mg/dL (70-200 mg/dL) 7.58 (7.35-7.45) 32.9 mmHg (35-42 mmHg) 109.1 mmHg (80-100 mmHg) 30.2 meq/L (20-26 meq/L) 60 meq/L 43 meq/L