Hyponatremia

Etiologies

• Medications: thiazide and thiazide-type diuretics, mannitol, IVIG, desmopressin (dDAVP), ecstasy (methylenedioxymethamphetamine), and some antidepressants, antiepileptics, and antipsychotics

Differential Diagnosis

• Pseudohyponatremia from lab error
• Translational hyponatremia from mannitol or hyperglycemia
• Hypovolemic
  • U_Na >20: Renal losses, including mineralocorticoid deficiency
  • U_Na <10: Non-renal losses
• Euvolemic
  • U_osm >100: SIADH, hypothyroidism, glucocorticoid deficiency
  • U_osm <100: Primary polydipsia, low solute intake
  • U_osm variable: Reset osmostat
• Hypervolemic
  • U_Na <10: CHD, cirrhosis, nephrosis
  • U_Na >20: Renal failure

Investigations

• Serum and urine osmolality and electrolytes (prior to treatment)
• TSH and AM cortisol

Diagnosis by Lab Criteria

• Serum Na (S_Na) <134?
• Measure serum osmolality (S_osm) and urea level (S_urea)
  • S_osm ≥ 280: normotonic/hypertonic
    • Differential includes pseudohyponatremia (from hyperlipidemia, hyperparaproteinemia, etc.), or presence of osmotically active substances (glucose, mannitol)
  • S_osm <280 mOsm/kg: true hyponatremia
    • Measure urine osmolality (U_osm)
    • U_osm <100 mOsm/kg: normal water excretion
      • Primary polydipsea or reset osmostat syndrome
    • U_osm ≥ 100 mOsm/kg: impaired water excretion
      • Exclude hypothyroidism and adrenal insufficiency with morning cortisol and TSH
      • Measure urine sodium (U_Na)
      • U_Na < 20 mmol/L: hypovolemia, including EABV depletion (heart failure, cirrhosis, nephrotic syndrome)
      • U_Na > 40 mmol/L: SIADH, reset ostmostat, renal salt wasting
        • Salt supplementation and water restriction
        • Normal S_urate and reduced FE_urate: SIADH
        • Hypouricemia and unchanged FE_urate: renal salt wasting
      • U_Na between 20 and 40 mmol/L
        • Bolus 2L/day normal saline for 2 days and trend sodium
        • If S_Na increases by ≥ 5 mmol/L: hypovolemia
        • If S_Na increases by <5 mmol/L: SIADH or reset ostmostat
          • FE_urea >55%, S_urate <0.24, and FE_urate >10%: SIADH
          • Oral or IV water-loading test: reset ostmostat

Management

• Depends on cause
• Goal rate of correction in chronic hyponatremia should be 4 to 6 mEq/L in 24 hours (max of 8 mEq) in order to reduce the risk of osmotic demyelination syndrome

Further Reading

• Milionis HJ, Liamis GL, and Elisaf MS. The hyponatremic patient: a systematic approach to laboratory diagnosis. CMAJ. 2002;166(8):1056-1062.