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Cleveland Clinic Journal of MedicineA Hidden Cause of Hypokalemia

Unveiling the Hidden Causes of Hypokalemia: A Case Study Linking Metabolic Alkalosis and Ectopic ACTH Production

A 21-year-old man presented with fatigue, psychosis, and significant weight gain, leading to the diagnosis of metabolic alkalosis and hypokalemia. This case study traces the diagnostic pathway, highlighting the critical role of urine chloride assessment and subsequent hormone evaluations, ultimately identifying an ectopic ACTH-producing tumor as the underlying cause.

Key Points:

  • Patient Presentation: 21-year-old male with fatigue, psychosis, and a 20-lb weight gain over six weeks; no gastrointestinal or urinary symptoms; no medications or substance use.
  • Physical Examination: Alert, oriented, clear lungs, normal cardiovascular and gastrointestinal findings, abdominal and back striae.
  • Vital Signs: Temperature 37.0°C, heart rate 60 bpm, respiratory rate 11 bpm, oxygen saturation 98%, blood pressure 153/92 mm Hg, BMI 34 kg/m².
  • Initial Laboratory Results: Blood gas analysis showed alkalemia (pH 7.55), elevated serum bicarbonate (34 mEq/L), and partially compensated respiratory alkalosis (pCO2 42 mm Hg).
  • Diagnosis: Primary metabolic alkalosis with respiratory compensation.
  • Urine Studies: Urine chloride level of 34 mmol/L indicating chloride-resistant metabolic alkalosis.
  • Renal Potassium Wasting: Elevated urine potassium-to-creatinine ratio (43.5 mmol/g) and fractional excretion of potassium (>9.3%).
  • Hormone Levels: Serum renin < 0.1 ng/mL per hour, serum aldosterone 3.1 ng/dL, and serum magnesium 2.0 mg/dL.
  • Hormone Testing: Elevated 24-hour urine cortisol and serum ACTH levels; high-dose dexamethasone suppression test showed less than 50% suppression of serum cortisol, indicating ectopic ACTH production.
  • Imaging Results: MRI revealed a 5-mm pituitary adenoma; PET scan identified a tracer-avid left lung perihilar nodule, confirming a pulmonary carcinoid tumor.
  • Treatment: Initial management with eplerenone and metyrapone, followed by surgical resection of the lung nodule. Post-surgery, ACTH levels normalized, resolving hypokalemia and hypertension.
  • Diagnostic Approach: Highlighted the importance of assessing spot urine chloride in diagnosing metabolic alkalosis and differentiating between volume-responsive and volume-resistant types.
  • Clinical Implications: Emphasized the role of hormone level evaluation and imaging in identifying ectopic ACTH sources and the effectiveness of targeted treatments for complex metabolic conditions.

HCN Medical Memo
Physicians should consider obtaining spot urine chloride levels when assessing patients with metabolic alkalosis to differentiate between volume-responsive and volume-resistant types, particularly in cases with unexplained symptoms and significant electrolyte imbalances.


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