Hydrochlorothiazide Will Lower Serum Sodium, Not Raise It
Hydrochlorothiazide (HCTZ) causes hyponatremia and should never be used to treat hypernatremia—it will worsen elevated sodium levels by impairing free water clearance while increasing sodium excretion. 1, 2
Mechanism of Sodium Lowering
HCTZ blocks sodium and chloride reabsorption in the distal convoluted tubule, increasing urinary sodium excretion by 5-10% of the filtered load. 1 However, the critical issue is that thiazides decrease free water clearance, which paradoxically leads to hyponatremia in clinical practice, not correction of hypernatremia. 3, 1
The FDA label explicitly states that HCTZ "increases the quantity of sodium traversing the distal tubule and the volume of water excreted," but with continued use, "compensatory mechanisms tend to increase this exchange and may produce excessive loss of potassium, hydrogen and chloride ions." 2 This natriuretic effect is accompanied by impaired water excretion, creating a net dilutional effect on serum sodium.
Clinical Evidence Against Use in Hypernatremia
A randomized controlled trial specifically tested HCTZ 25 mg daily in 50 ICU patients with hypernatremia (serum sodium ≥143 mmol/L). 4 The study found no significant difference in serum sodium reduction between HCTZ and placebo (both groups decreased by median 4 mmol/L, P=0.32), and no difference in urinary sodium excretion (P=0.34) or duration of severe hypernatremia (P=0.91). 4 This demonstrates HCTZ is ineffective for treating hypernatremia.
Risk of Severe Hyponatremia
Multiple case reports document severe, life-threatening hyponatremia with HCTZ use:
- A 69-year-old developed serum sodium of 120 mmol/L within 2 weeks of starting HCTZ, requiring hospitalization and free water restriction. 5
- A 72-year-old presented with hyponatremic encephalopathy with serum sodium of 100 mmol/L while on HCTZ 25 mg daily. 6
The 2022 ACC/AHA/HFSA guidelines explicitly state that all diuretics must be held immediately when sodium falls to 118 mEq/L, and should not be restarted until sodium normalizes above 135 mEq/L. 7
Contrast with Loop Diuretics
Unlike HCTZ, loop diuretics (furosemide, torsemide, bumetanide) increase sodium excretion by 20-25% of filtered load and enhance free water clearance, maintaining efficacy even in severe renal impairment. 1 This is why the 2022 guidelines note that "vasopressin antagonists may be helpful in the acute management of volume overload to decrease congestion while maintaining serum sodium" when hyponatremia complicates heart failure management—not thiazides. 3
Clinical Bottom Line
HCTZ is contraindicated in hypernatremia. It increases urinary sodium loss while impairing free water excretion, leading to hyponatremia as a well-documented adverse effect. 1, 2, 5, 6 For hypernatremia management, free water replacement is the primary treatment, not thiazide diuretics.