What is the cause of hyponatremia in a patient with type 2 diabetes (T2D) and hypertension on losartan (Angiotensin II receptor antagonist), metformin (Biguanide), and atorvastatin (HMG-CoA reductase inhibitor) presenting with abdominal pain and pancreatitis?

Hyponatremia in Acute Pancreatitis: Likely SIADH

In this patient with acute pancreatitis, the most likely cause of hyponatremia is Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH), triggered by the acute inflammatory stress of pancreatitis itself. 1, 2

Primary Mechanism: SIADH from Acute Pancreatitis

Acute pancreatitis is a well-established nonosmotic stimulus for arginine vasopressin (AVP) release, leading to hyponatremia. 2 The pain, nausea, and physiologic stress associated with pancreatitis trigger inappropriate ADH secretion despite low serum osmolality, impairing free-water excretion and causing dilutional hyponatremia. 2

• This represents a SIAD (Syndrome of Inappropriate Antidiuresis) state where water retention occurs followed by physiologic natriuresis—fluid balance is maintained at the expense of plasma sodium concentration. 2
• The patient would typically present as euvolemic on examination (no edema, no orthostatic hypotension, normal skin turgor, moist mucous membranes). 1

Diagnostic Confirmation

To confirm SIADH in this clinical context, you should obtain: 1, 2, 3

• Serum osmolality (expect <275 mOsm/kg)
• Urine osmolality (expect >500 mOsm/kg—inappropriately concentrated)
• Urine sodium (expect >20-40 mEq/L)
• Serum uric acid (<4 mg/dL has 73-100% positive predictive value for SIADH) 1, 3
• TSH and cortisol to exclude hypothyroidism and adrenal insufficiency 1, 3

Physical examination alone is unreliable for volume status assessment (sensitivity 41.1%, specificity 80%), so laboratory confirmation is essential. 1, 3

Alternative Considerations (Less Likely)

Losartan-Related Hyponatremia

While losartan can cause hyponatremia through volume depletion and activation of the renin-angiotensin system 4, this is typically seen in patients who are volume- or salt-depleted from high-dose diuretics. 4 This patient is not on diuretics, making this mechanism less likely as the primary cause.

Metformin

Metformin does not directly cause hyponatremia. 5 It can be used safely in patients with mild hyponatremia but should be held if renal function deteriorates. 5

Biliary Fluid Loss

While external biliary drainage can cause hyponatremia through sodium-containing fluid loss 6, this patient has no indication of biliary drainage or cholecystostomy tube placement, making this irrelevant.

Management Approach

For Mild-Moderate Hyponatremia (Na 120-135 mEq/L)

Implement fluid restriction to 1 L/day as first-line treatment. 1, 2 This is the cornerstone of SIADH management in asymptomatic or mildly symptomatic patients. 1, 2

• Add oral sodium chloride 100 mEq three times daily if no response to fluid restriction alone. 1, 2
• Monitor serum sodium every 24 hours initially, then adjust frequency based on response. 1

For Severe Symptomatic Hyponatremia (Na <120 mEq/L with neurological symptoms)

Administer 3% hypertonic saline immediately with target correction of 6 mmol/L over 6 hours or until symptoms resolve. 1, 2

• Never exceed 8 mmol/L correction in 24 hours to prevent osmotic demyelination syndrome. 1, 2
• Monitor serum sodium every 2 hours during initial correction. 1, 2
• Transfer to ICU for close monitoring. 2

Critical Safety Considerations

The maximum correction rate must not exceed 8 mmol/L in 24 hours. 1, 2 Overly rapid correction causes osmotic demyelination syndrome, which manifests as dysarthria, dysphagia, oculomotor dysfunction, and quadriparesis typically 2-7 days after rapid correction. 1

Common Pitfalls to Avoid

• Do not use normal saline for SIADH—this is euvolemic hyponatremia requiring fluid restriction, not volume repletion. 1, 3
• Do not ignore mild hyponatremia (130-135 mmol/L)—even mild hyponatremia increases fall risk (21% vs 5%) and mortality (60-fold increase). 1
• Do not fail to treat the underlying cause—treating the pancreatitis itself will often lead to resolution of the SIADH. 2
• Avoid fluid restriction in patients requiring aggressive hydration for pancreatitis management—this creates a clinical dilemma requiring careful sodium monitoring and possible pharmacologic intervention. 5

Medication Adjustments

• Continue metformin if renal function remains normal (eGFR >60 mL/min). 5
• Continue losartan unless the patient develops significant volume depletion or renal dysfunction. 4
• Continue atorvastatin—no direct relationship to hyponatremia. 5