What are the potential causes of this patient's hyponatremia?

Causes of Hyponatremia and Essential Laboratory Workup

The most critical step is to immediately assess volume status and obtain serum/urine osmolality, urine sodium, and urine electrolytes to determine the underlying mechanism—hypovolemic, euvolemic, or hypervolemic hyponatremia—as this directly guides treatment and prevents potentially fatal complications. 1, 2

Primary Mechanisms and Causes by Volume Status

Hypovolemic Hyponatremia (True Volume Depletion)

• Excessive diuretic use (particularly thiazides and loop diuretics) is a leading iatrogenic cause 2
• Gastrointestinal losses from vomiting, diarrhea, or severe burns with inadequate sodium replacement 3
• Cerebral salt wasting syndrome in neurosurgical patients, characterized by excessive natriuresis despite volume depletion 2
• Renal salt wasting from intrinsic kidney disease 3

Euvolemic Hyponatremia (Normal Volume Status)

• Syndrome of Inappropriate Antidiuretic Hormone (SIADH) is the most common cause in this category 2, 4
• Malignancies: small cell lung cancer (affects 1-5% of patients), pancreatic cancer, lymphomas 2
• High-risk medications: carbamazepine, oxcarbazepine, SSRIs, vincristine, cyclophosphamide, desmopressin, and trazodone 5, 2
• CNS disorders: subarachnoid hemorrhage, meningitis, encephalitis 2
• Pulmonary diseases: pneumonia, tuberculosis 3
• Hypothyroidism and adrenal insufficiency 5

Hypervolemic Hyponatremia (Volume Overload)

• Cirrhosis with portal hypertension (occurs in ~60% of cirrhotic patients) due to non-osmotic vasopressin hypersecretion and enhanced proximal sodium reabsorption 2, 6
• Congestive heart failure from reduced cardiac output triggering neurohormonal activation with increased ADH release 2, 6
• Nephrotic syndrome and chronic kidney disease with impaired free water excretion 5

Essential Laboratory Workup

Initial Blood Tests (Must Obtain)

• Serum osmolality to confirm true hypotonic hyponatremia vs. pseudohyponatremia 1, 2
• Serum glucose (adjust sodium by 1.6 mEq/L for each 100 mg/dL glucose >100 mg/dL to rule out hyperglycemic pseudohyponatremia) 1
• Serum creatinine and BUN (elevated in hypovolemic states; helps assess renal function) 1
• Serum uric acid (<4 mg/dL has 73-100% positive predictive value for SIADH) 1, 2
• Thyroid-stimulating hormone (TSH) to exclude hypothyroidism 1
• Morning cortisol if adrenal insufficiency suspected 1
• Liver function tests including albumin if cirrhosis suspected 1

Critical Urine Tests (Simultaneously Obtain)

• Urine osmolality (>300-500 mOsm/kg with low serum osmolality suggests SIADH or renal salt wasting) 1, 2
• Urine sodium concentration:
  • <30 mmol/L suggests hypovolemic hyponatremia (71-100% positive predictive value for saline response) 1, 2
  • >20-40 mmol/L with high urine osmolality suggests SIADH or cerebral salt wasting 1, 2
• Spot urine sodium/potassium ratio (>1 correlates with 24-hour sodium excretion >78 mmol/day with ~90% accuracy) 1

Volume Status Assessment (Clinical Examination)

• Hypovolemia indicators: orthostatic hypotension, dry mucous membranes, decreased skin turgor, sunken eyes, furrowed tongue 1
• Hypervolemia indicators: peripheral edema, ascites, jugular venous distention, pulmonary congestion 1
• Euvolemia: absence of both hypovolemic and hypervolemic signs 1

High-Risk Populations Requiring Immediate Attention

• Patients on high-risk medications: desmopressin, antiepileptics (carbamazepine), chemotherapy (cyclophosphamide, vincristine), SSRIs, trazodone 5, 2
• Neurosurgical patients: distinguish cerebral salt wasting from SIADH as treatments are opposite 1
• Cirrhotic patients: sodium <130 mmol/L increases risk of spontaneous bacterial peritonitis (OR 3.40), hepatorenal syndrome (OR 3.45), and hepatic encephalopathy (OR 2.36) 1
• Heart failure patients: hyponatremia indicates worsening hemodynamic status and increased mortality 1, 6

Common Diagnostic Pitfalls to Avoid

• Ignoring mild hyponatremia (130-135 mmol/L) as clinically insignificant—even mild hyponatremia increases fall risk (21% vs. 5%), fractures, and mortality (60-fold increase when <130 mmol/L) 1, 4
• Failing to assess volume status accurately—physical examination alone has poor sensitivity (41.1%) and specificity (80%); use urine sodium to confirm 1
• Obtaining ADH or natriuretic peptide levels—not supported by evidence and delays treatment 1
• Misdiagnosing SIADH in neurosurgical patients—cerebral salt wasting is more common and requires opposite treatment (volume replacement vs. fluid restriction) 1