What could be the cause of metabolic alkalosis in a euvolemic patient with no diuretic use, no nasogastric (NG) tubes, no vomiting, and no electrolyte imbalances?

Metabolic Alkalosis in Euvolemic Patients Without Common Causes

In a euvolemic patient with metabolic alkalosis and no diuretic use, vomiting, NG tubes, or apparent electrolyte imbalances, you should strongly consider Bartter syndrome or Gitelman syndrome as the underlying cause. 1, 2

Primary Diagnostic Consideration: Salt-Losing Tubulopathies

Bartter syndrome is the most likely diagnosis in this clinical scenario, particularly if the patient presents with:

• Hypokalemic metabolic alkalosis as a hallmark finding despite no obvious external losses 1
• Hypochloremia (often missed on routine panels but critical to the diagnosis) 3
• Elevated urinary chloride (fractional excretion >0.5%) despite systemic hypochloremia, distinguishing this from volume depletion states 2, 3
• Normal to low blood pressure despite the metabolic derangements 1

Pathophysiology

Bartter syndrome results from impaired salt reabsorption in the thick ascending limb of the loop of Henle, creating a state that mimics chronic loop diuretic use—but without actual diuretic exposure 1, 3. This leads to:

• Renal tubular salt wasting with compensatory aldosterone activation 2
• Paradoxical aciduria (acid urine despite systemic alkalosis) due to enhanced distal hydrogen ion secretion driven by increased sodium reabsorption 2
• Secondary hyperaldosteronism maintaining the alkalosis 1, 4

Critical Diagnostic Steps

Measure Urinary Chloride Concentration

This single test distinguishes between chloride-responsive and chloride-resistant alkalosis 5, 4:

• Urinary chloride >20 mEq/L suggests chloride-resistant alkalosis, pointing toward Bartter or Gitelman syndrome 5
• Calculate fractional excretion of chloride—values >0.5% despite hypochloremia are highly suggestive of Bartter syndrome 2, 3

Assess for Subtle Electrolyte Abnormalities

While you state "no electrolyte imbalances," recheck specifically for 1:

• Hypokalemia (may be mild, around 3.0-3.5 mmol/L, and easily overlooked) 1
• Hypomagnesemia (present in up to 60% of cases, often <0.70 mmol/L) 1
• Hypochloremia (frequently missed but pathognomonic) 3

Measure Renin and Aldosterone Levels

Elevated plasma renin and aldosterone with normal blood pressure strongly suggests Bartter syndrome 6. This distinguishes it from primary hyperaldosteronism, which presents with hypertension 4.

Additional Diagnostic Considerations

Occult Diuretic Use

Always consider surreptitious diuretic use, particularly in healthcare workers or patients with eating disorders 1, 4. Request:

• Urine diuretic screen (can detect loop and thiazide diuretics) 4
• Careful medication reconciliation including over-the-counter products 4

Genetic Testing

If Bartter or Gitelman syndrome is suspected, genetic testing provides definitive diagnosis 5. Consider this especially if:

• History of polyhydramnios or premature birth 5
• Family history of similar symptoms 1
• Nephrocalcinosis on renal ultrasound 5

Less Common Causes to Consider

Apparent Mineralocorticoid Excess Syndromes

• Licorice ingestion (glycyrrhizic acid inhibits 11β-hydroxysteroid dehydrogenase) 7, 4
• Cushing syndrome (cortisol excess) 4
• Congenital adrenal hyperplasia (11β-hydroxylase or 17α-hydroxylase deficiency) 7

These typically present with hypertension, distinguishing them from Bartter syndrome 4.

Excess Alkali Administration

• Milk-alkali syndrome from calcium carbonate supplements 4, 8
• Citrate, lactate, or acetate from blood products or parenteral nutrition 7, 8

Treatment Approach

Once Bartter syndrome is confirmed, treatment focuses on salt and electrolyte supplementation 1, 5:

First-Line Therapy

• Sodium chloride supplementation at 5-10 mmol/kg/day (physiologic replacement for renal salt wasting) 1, 5
• Potassium chloride (not potassium citrate, which worsens alkalosis) 1, 5
• NSAIDs (indomethacin or ibuprofen) to reduce prostaglandin-mediated salt wasting, especially in symptomatic patients 1, 5
• Gastric acid inhibitors when using NSAIDs to prevent gastrointestinal complications 1

Avoid Common Pitfalls

Do not use potassium-sparing diuretics, ACE inhibitors, or ARBs routinely 1. While they improve hypokalemia, they worsen the underlying salt wasting and risk life-threatening hypovolemia 1. Reserve these only for severe refractory cases under specialist guidance 1.

Do not use thiazide diuretics to reduce hypercalciuria—they cause critical hypovolemia in salt-wasting states 1.

Key Clinical Pearls

• Bartter syndrome mimics chronic loop diuretic use but occurs without diuretic exposure 1, 3
• Urinary chloride >20 mEq/L distinguishes this from volume depletion alkalosis (where urinary chloride is typically <10 mEq/L) 5, 4
• The combination of metabolic alkalosis, hypokalemia, and normal blood pressure should immediately trigger consideration of Bartter or Gitelman syndrome 1, 4
• Hypochloremia maintains the alkalosis by limiting bicarbonate excretion, making chloride repletion essential 2, 3