What is the approach to the workup of hyponatremia?

Workup of Hyponatremia

The initial workup of hyponatremia should include measuring serum and urine osmolality, urine electrolytes, uric acid, and assessment of extracellular fluid volume status to determine the underlying cause. 1, 2

Initial Assessment

• Hyponatremia is defined as serum sodium <135 mmol/L, with severity classified as mild (126-135 mmol/L), moderate (120-125 mmol/L), and severe (<120 mmol/L) 2, 3
• A serum Na value <131 mmol/L should prompt a comprehensive workup 1
• Check serum osmolality to distinguish between hypotonic, isotonic, and hypertonic hyponatremia 2, 4
• Normal or high serum osmolality may indicate pseudohyponatremia from laboratory error, hyperglycemia, or hypertriglyceridemia 1, 4

Volume Status Assessment

• Categorize patients into one of three volume status categories: hypovolemic, euvolemic, or hypervolemic 5, 3
• Physical examination alone has been shown to be inaccurate for determining ECF status (sensitivity 41.1%, specificity 80%) 1
• Use laboratory parameters to supplement clinical assessment of volume status 5

Volume Status Indicators:

• Hypovolemic signs: Orthostatic hypotension, dry mucous membranes, decreased skin turgor 1
• Euvolemic signs: No edema, normal vital signs, normal jugular venous pressure 2
• Hypervolemic signs: Edema, ascites, elevated jugular venous pressure 2, 5

Laboratory Evaluation

• Essential tests: 1, 2, 5

  • Serum sodium and osmolality
  • Urine sodium and osmolality
  • Serum uric acid
  • Renal function tests (BUN, creatinine)
  • Thyroid function tests
  • Morning cortisol

• Interpretive findings: 1, 6

  • Urinary Na <30 mmol/L has a positive predictive value of 71-100% for response to 0.9% saline infusion
  • Serum uric acid <4 mg/dL has a positive predictive value of 73-100% for SIADH
  • Fractional excretion of sodium and urea are associated with saline responsiveness

Diagnostic Algorithm

1. Rule out pseudohyponatremia: 1, 4

   • Check serum osmolality (normal: 275-290 mOsm/kg)
   • If normal/high osmolality, consider hyperglycemia, mannitol, or laboratory error

2. For hypotonic hyponatremia (low serum osmolality): 1, 2

   • Assess volume status and categorize as hypovolemic, euvolemic, or hypervolemic

3. For hypovolemic hyponatremia: 2, 5

   • Check urine sodium: <20 mEq/L suggests extrarenal losses (vomiting, diarrhea)
   • Check urine sodium: >20 mEq/L suggests renal losses (diuretics, cerebral salt wasting, adrenal insufficiency)

4. For euvolemic hyponatremia: 1, 6

   • Rule out hypothyroidism, hypocortisolism, and polydipsia
   • Check urine osmolality: >100 mOsm/kg with urine sodium >40 mEq/L suggests SIADH

5. For hypervolemic hyponatremia: 1, 2

   • Rule out cirrhosis, congestive heart failure, and renal failure

Special Considerations

• In neurosurgical patients, distinguish between SIADH and cerebral salt wasting (CSW), as treatment approaches differ significantly 1, 2
• Obtaining levels of hormones such as ADH and natriuretic peptides is not supported by the literature (class III evidence) 1
• A urinary sodium level <30 mmol/L has a positive predictive value of 71-100% for an infusion of 0.9% saline to increase the serum sodium level 1
• Misdiagnosis of volume status can lead to inappropriate therapy and worsened outcomes 5

Common Pitfalls to Avoid

• Relying solely on physical examination to determine volume status 1, 5
• Failing to recognize cerebral salt wasting in neurosurgical patients 2, 5
• Overlooking medication causes of hyponatremia 5
• Failing to identify the underlying cause before initiating treatment 2
• Misdiagnosing SIADH when other causes are present 6

By following this systematic approach to the workup of hyponatremia, clinicians can accurately diagnose the underlying cause and implement appropriate treatment strategies to improve patient outcomes and reduce morbidity and mortality.