What is causing hyponatremia in a patient taking HCTZ (Hydrochlorothiazide), Losartan, Amlodipine, Rabeprazole, and Balsalazide with a history of alcohol use?

Hyponatremia in a Patient on HCTZ: Cause and Management

Primary Cause

HCTZ (hydrochlorothiazide) is the most likely culprit for this patient's hyponatremia (sodium 128 mEq/L). Thiazide diuretics are one of the most common causes of severe hyponatremia, far more so than loop diuretics, and can cause rapid development of severe hyponatremia in susceptible patients 1, 2. The mechanism involves impaired urinary dilution through multiple pathways: inhibition of sodium and chloride transport at cortical diluting sites, stimulation of vasopressin release, reduced glomerular filtration with enhanced proximal water reabsorption, and possibly direct effects on collecting duct water flow 2. Elderly patients and those with high water intake are particularly vulnerable 2.

Contributing Factors

Thiazide-Specific Mechanisms

• HCTZ blocks sodium and chloride reabsorption in the distal tubule, leading to compensatory mechanisms that can produce excessive loss of potassium, hydrogen, and chloride ions 3
• Thiazide-induced hyponatremia is associated with increased water intake (polydipsia) and impaired urea-mediated water excretion, even at low plasma ADH levels 4
• Patients with thiazide-induced hyponatremia demonstrate markedly impaired free water excretion despite suppressed ADH and aquaporin-2 levels 4

Alcohol Use History

• Chronic alcohol use can contribute through multiple mechanisms: poor nutritional intake leading to low urea excretion (beer potomania), potential liver dysfunction affecting fluid balance, and increased risk of osmotic demyelination syndrome during correction 5
• Alcohol-related malnutrition increases susceptibility to severe hyponatremia and complications from correction 5

Losartan (Minor Contributor)

• While ARBs like losartan can rarely cause hyponatremia, this is uncommon compared to thiazides 6
• The combination of HCTZ/losartan makes HCTZ the primary suspect given its well-established association with hyponatremia 1, 2

Other Medications (Unlikely Contributors)

• Amlodipine, rabeprazole, and balsalazide are not recognized causes of hyponatremia 5

Immediate Management Algorithm

Step 1: Discontinue HCTZ Immediately

• Stop the thiazide diuretic immediately - this is the most critical intervention 7, 1
• Continue losartan if blood pressure control is needed, as it is less likely the primary cause 6

Step 2: Assess Volume Status and Symptoms

• Check for signs of hypovolemia: orthostatic hypotension, dry mucous membranes, decreased skin turgor 5
• Check for hypervolemia: peripheral edema, ascites, jugular venous distention 5
• Assess symptom severity: confusion, weakness, seizures, or altered mental status 5

Step 3: Initial Laboratory Workup

• Serum osmolality, urine osmolality, and urine sodium concentration 5
• Serum potassium, magnesium, creatinine, and BUN 8, 5
• Thyroid function (TSH) to rule out hypothyroidism 5
• Uric acid (low levels <4 mg/dL suggest SIADH) 5

Step 4: Treatment Based on Severity

For Sodium 128 mEq/L (Mild-Moderate, Asymptomatic):

• Implement fluid restriction to 1-1.5 L/day 5
• Monitor serum sodium every 24 hours initially 5
• Replace potassium if depleted (thiazides commonly cause hypokalemia which must be corrected) 8, 2
• Consider magnesium supplementation if levels are low, as hypomagnesemia often coexists with thiazide use 9

Critical Warning About Rapid Correction:

• Inadvertent rapid correction is common in thiazide-induced hyponatremia because diluting ability is restored when the diuretic is discontinued and volume deficits are repaired 2
• Maximum correction must not exceed 8 mmol/L in 24 hours to prevent osmotic demyelination syndrome 5
• This patient with alcohol history requires even more cautious correction: 4-6 mmol/L per day maximum 5
• Hypokalemia increases susceptibility to osmotic demyelination syndrome, making potassium replacement essential 2

Step 5: Monitoring During Correction

• Check sodium levels every 4-6 hours during active correction 5
• If correction exceeds 6 mmol/L in first 12 hours, consider administering D5W or desmopressin to slow correction 5
• Monitor for signs of osmotic demyelination syndrome: dysarthria, dysphagia, oculomotor dysfunction, quadriparesis (typically 2-7 days after rapid correction) 5

Long-Term Management

Antihypertensive Adjustment

• Do not restart thiazide diuretics - patients with thiazide-induced hyponatremia should avoid future thiazide use 7, 2
• Continue losartan for blood pressure control 6
• Consider adding amlodipine dose adjustment or alternative antihypertensive if needed 8

Dietary Counseling

• Sodium intake: 2-2.5 g/day (88-110 mmol/day) 5
• Avoid excessive water intake, particularly in context of alcohol use 4, 2
• Address alcohol use given its contribution to hyponatremia risk and nutritional status 5

Follow-Up Monitoring

• Recheck sodium in 1 week after stabilization 5
• Monitor electrolytes (sodium, potassium, magnesium) every 1-2 weeks initially, then monthly once stable 8

Common Pitfalls to Avoid

• Ignoring mild hyponatremia (128 mEq/L) - even this level increases fall risk and mortality 5
• Allowing correction >8 mmol/L in 24 hours - particularly dangerous in patients with alcohol history 5, 2
• Failing to replace potassium deficits - hypokalemia increases osmotic demyelination risk and contributes to sodium correction 2
• Restarting thiazides - patients with documented thiazide-induced hyponatremia should permanently avoid this drug class 7, 2
• Using normal saline without assessing volume status - may worsen hypervolemic hyponatremia if present 5