β2-agonist–induced transcellular hypokalemia

Electrolyte Disordersmedium

A 25-year-old woman with a medical history of asthma and hypothyroidism presents to the emergency department with 1 week of progressive wheezing and shortness of breath. Her current medications include a fluticasone/salmeterol inhaler and levothyroxine sodium, and she reports using an albuterol metered-dose inhaler every 1–2 hours without relief. On examination, her BP is 110/62 mm Hg, heart rate is 100/min, respiratory rate is 24/min, her oxygen saturation is 89% while breathing supplemental oxygen at 2 L/min, and body mass index (BMI) is 22 kg/m². She appears in respiratory distress, with diffuse wheezing in all lung fields. She has reduced muscle strength in her legs bilaterally. She is treated with albuterol nebulizers, methylprednisolone, and 2 L of normal saline IV. Laboratory data: serum sodium 139 mEq/L (reference 136–145); potassium 2.8 mEq/L (3.5–5.0); chloride 112 mEq/L (98–106); total CO₂ 20 mEq/L (23–28); BUN 16 mg/dL (8–20); creatinine 0.8 mg/dL (0.5–1.1); glucose 95 mg/dL (70–99, fasting); thyroid-stimulating hormone 3.5 µU/mL (0.5–4.0); free thyroxine 1.0 ng/dL (0.8–1.8). Arterial blood gas: arterial pH 7.35 (7.38–7.44); PaCO₂ 38 mm Hg (38–42). Urine, spot: sodium 18 mEq/L (varies); potassium 10 mEq/L (varies); chloride 28 mEq/L (varies); creatinine 85 mg/dL (varies). A urinalysis reveals a pH of 5.0, with negative blood and protein. Which ONE of the following is the MOST likely cause of this patient’s hypokalemia?

  1. A.Surreptitious diuretic use
  2. B.AlbuterolCorrect
  3. C.Renal tubular acidosis
  4. D.Hypokalemic periodic paralysis

Explanation

The most likely cause of this patient’s hypokalemia is albuterol administration. The use of albuterol, a β-2-adrenergic agonist, causes Na⁺/K⁺ ATPase pump stimulation in skeletal muscles and intracellular potassium shifting, leading to hypokalemia. Hypokalemic periodic paralysis (HPP) causes proximal muscle weakness accompanied by hypokalemia. Precipitating events include strenuous exercise, fasting, and a carbohydrate-rich diet. This condition may be familial. The inheritance pattern is autosomal dominant due to mutations in the CACNA1S (a calcium channel subunit expressed in skeletal muscle), SCN4A (a skeletal muscle sodium channel), or KCNE3 (a skeletal muscle potassium channel) gene. Acquired causes of HPP are associated with thyrotoxicosis, but thyroid levels here are normal. She has no prior history of hypokalemia-related events, and the recent frequent use of albuterol makes HPP less likely. Although renal tubular acidosis can cause hypokalemia and a normal–anion gap metabolic acidosis, her acidemia is mild, and she does not have a medical history consistent with an acquired renal tubular acidosis (e.g., medication use, Sjögren syndrome). The administration of normal saline may have contributed to the elevated serum chloride level. The clinical context of asthma and β-agonist use makes renal tubular acidosis less likely. Surreptitious diuretic use can cause hypokalemia, but this would typically present with a metabolic alkalosis, not an acidosis. A low serum chloride level is usually seen due to sodium and chloride losses. The combination of hypokalemia and recent β-agonist use is most consistent with potassium shifting due to β-agonist administration.

Why each option

A.
Diuretics cause hypokalemia with metabolic alkalosis and low serum chloride, the opposite of her hyperchloremic acidosis with low urine potassium.
B.
Correct. Hourly albuterol stimulates skeletal muscle Na⁺/K⁺-ATPase, shifting potassium into cells; low urine potassium confirms no kidney wasting.
C.
Mild hyperchloremic acidosis follows 2 L of normal saline, and an acidic urine pH of 5.0 without risk factors argues against distal RTA.
D.
Hypokalemic periodic paralysis requires prior episodes or thyrotoxicosis; her thyroid tests are normal and frequent albuterol explains the transcellular shift.

Reference: Palmer BF, Clin J Am Soc Nephrol 2015 (regulation of potassium homeostasis); Kardalas E, Endocr Connect 2018 (hypokalemia: clinical update)

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