In a patient with serum sodium 127 mmol/L, chloride 95 mmol/L, blood urea nitrogen 17 mg/dL, and creatinine 0.88 mg/dL, what is the most likely cause of the hyponatremia?

Likely Cause of Hyponatremia

Based on the laboratory values provided (sodium 127 mmol/L, chloride 95 mmol/L, BUN 17 mg/dL, creatinine 0.88 mg/dL), the most likely cause is euvolemic hyponatremia, with SIADH (Syndrome of Inappropriate Antidiuretic Hormone secretion) being the primary consideration, though the diagnosis requires additional workup to determine volume status and exclude other causes. 1

Initial Diagnostic Approach

The serum sodium of 127 mmol/L represents moderate hyponatremia that warrants comprehensive evaluation. 1 The normal creatinine (0.88 mg/dL) and relatively normal BUN (17 mg/dL) suggest preserved renal function and argue against severe volume depletion or renal failure as primary causes. 1

Key diagnostic steps include:

• Assess volume status clinically by examining for orthostatic hypotension, dry mucous membranes, decreased skin turgor (hypovolemia), versus peripheral edema, ascites, jugular venous distention (hypervolemia), versus absence of these findings (euvolemia). 1, 2 However, physical examination alone has poor accuracy (sensitivity 41.1%, specificity 80%), so laboratory confirmation is essential. 1, 3

• Measure serum and urine osmolality to confirm hypoosmolar hyponatremia and assess urinary concentration. 1, 3 Urine osmolality >100 mOsm/kg indicates impaired free water excretion. 1

• Check urine sodium concentration to differentiate causes. 1, 3, 2 Urine sodium >20-40 mEq/L with euvolemia strongly suggests SIADH. 1, 3 Urine sodium <30 mmol/L has 71-100% positive predictive value for hypovolemic hyponatremia responsive to saline. 1, 2

• Obtain serum uric acid, as levels <4 mg/dL have 73-100% positive predictive value for SIADH. 1, 3, 2

Most Likely Diagnostic Categories

Euvolemic Hyponatremia (SIADH) - Most Probable

SIADH is characterized by:

• Hypoosmolar hyponatremia with inappropriately concentrated urine (>300-500 mOsm/kg) 1, 3
• Elevated urine sodium (>20-40 mEq/L) despite low serum sodium 1, 3
• Clinical euvolemia (no edema, no orthostatic hypotension, normal skin turgor) 1, 3
• Normal thyroid, adrenal, and renal function 3

Common causes include: malignancies (especially lung cancer), CNS disorders, pulmonary diseases, medications (SSRIs, carbamazepine, NSAIDs, opioids, chemotherapy), postoperative states, pain, nausea, and stress. 1, 3

Hypovolemic Hyponatremia - Consider If Volume Depleted

This would present with clinical signs of dehydration and typically urine sodium <30 mmol/L (extrarenal losses) or >20 mmol/L (renal losses from diuretics, salt-wasting nephropathy, adrenal insufficiency). 1, 3, 2 The normal creatinine makes severe volume depletion less likely but does not exclude it. 1

Hypervolemic Hyponatremia - Less Likely Given Normal Creatinine

This occurs in heart failure, cirrhosis, or nephrotic syndrome with visible edema and ascites. 1 The normal creatinine and absence of mentioned volume overload signs make this less probable. 1

Critical Diagnostic Distinctions

In patients with neurological conditions or recent neurosurgery, distinguish SIADH from cerebral salt wasting (CSW):

• SIADH: Euvolemic, normal CVP (6-10 cm H₂O), treated with fluid restriction 1, 2
• CSW: Hypovolemic, low CVP (<6 cm H₂O), requires volume and sodium replacement, never fluid restriction 1, 2

Misdiagnosis leads to opposite and potentially harmful treatments. 1, 2

Additional Workup Needed

• Thyroid function (TSH) to exclude hypothyroidism 1, 3
• Morning cortisol to exclude adrenal insufficiency 3
• Medication review for drugs causing SIADH (diuretics, antidepressants, anticonvulsants, antipsychotics) 1, 4
• Assess for underlying malignancy if SIADH confirmed, especially lung cancer 1, 3

Common Pitfalls to Avoid

• Do not rely solely on physical examination for volume status determination given its poor sensitivity and specificity. 1, 3, 2
• Do not delay treatment while pursuing diagnostic workup if patient is symptomatic. 5
• Do not obtain ADH or natriuretic peptide levels, as these are not supported by evidence and delay diagnosis. 1, 3
• Do not assume pseudohyponatremia without checking serum osmolality, especially if hyperglycemia or hyperlipidemia present. 1, 5