Can Hydrochlorothiazide (HCTZ) cause hyponatremia?

Hydrochlorothiazide and Hyponatremia

Yes, hydrochlorothiazide (HCTZ) can cause hyponatremia, with approximately 30% of patients on ongoing thiazide therapy developing this potentially serious complication. 1

Mechanism and Risk

Thiazide-induced hyponatremia occurs through several mechanisms:

• Impaired urinary dilution capacity
• Excessive fluid intake
• Sodium and potassium depletion
• Reduced ability to excrete free water
• Reduced distal delivery of filtrate
• Direct inhibition of the sodium-chloride cotransporter
• Increased collecting duct permeability to water 2

Risk Factors

The primary risk factors for thiazide-induced hyponatremia include:

• Advanced age (each 10-year increment doubles the risk)
• Low body weight (5 kg decrease increases risk by 27%)
• Female sex
• Low serum potassium levels (hypokalemia)
• Possibly low body mass 3

Clinical Presentation

Hyponatremia from HCTZ can present with:

• Generalized weakness
• Confusion
• Headache
• Nausea
• In severe cases: seizures and coma 4, 2

While many cases develop within the first few weeks of starting therapy, hyponatremia can also occur after months or years of use 2.

Management

When hyponatremia is detected in a patient taking HCTZ:

1. Discontinue the thiazide diuretic - This is the cornerstone of management 2
2. Implement fluid restriction - Typically to 1000 mL/day for moderate to severe hyponatremia 5
3. Provide cation repletion as needed
4. Monitor serum sodium levels every 4-6 hours during active correction 5
5. Control correction rate - Target 4-6 mmol/L in 24 hours, not exceeding 8 mmol/L in 24 hours to avoid osmotic demyelination syndrome 5
6. For severe symptomatic hyponatremia - Consider 3% hypertonic saline 2

Alternative Diuretics

When a diuretic is still needed after HCTZ-induced hyponatremia:

• Loop diuretics may be considered as they have a different mechanism of action
• If eGFR is <30 mL/min/m², a loop diuretic should be used rather than thiazide diuretics 6
• For patients requiring a thiazide-type diuretic, chlorthalidone or indapamide may be preferable over HCTZ for hypertension management 6, 7

Prevention

To prevent thiazide-induced hyponatremia:

• Use caution when prescribing HCTZ to elderly patients with low body mass 3
• Monitor serum electrolytes regularly, especially in high-risk patients
• Consider lower doses in susceptible individuals
• Educate patients about symptoms of hyponatremia and when to seek medical attention

Clinical Implications

The number needed to harm (to cause one excess case of hyponatremia in 5 years) with thiazide use is approximately 15 1. While most cases are mild or moderate, severe hyponatremia can lead to significant morbidity and mortality, making awareness of this complication essential for clinicians prescribing HCTZ 4.

For patients who have experienced HCTZ-induced hyponatremia, alternative antihypertensive medications should be considered, as recurrence is likely with rechallenge.