What is the step‑by‑step approach to diagnosing hyponatremia?

Diagnostic Approach to Hyponatremia

The diagnosis of hyponatremia requires a systematic evaluation beginning with confirmation of true hypotonic hyponatremia, followed by assessment of volume status and measurement of urine osmolality and sodium to determine the underlying mechanism. 1

Step 1: Confirm True Hyponatremia and Assess Severity

• Measure serum sodium and serum osmolality to confirm hyponatremia (serum sodium <135 mmol/L) and exclude pseudohyponatremia from hyperglycemia or hyperlipidemia 1, 2
• Calculate corrected sodium if hyperglycemia is present: add 1.6 mEq/L to measured sodium for each 100 mg/dL glucose above 100 mg/dL 1
• Classify severity as mild (126-135 mmol/L), moderate (120-125 mmol/L), or severe (<120 mmol/L) to guide urgency of treatment 1
• Assess symptom severity immediately, as severe symptoms (seizures, coma, altered mental status) require emergency hypertonic saline regardless of sodium level 1, 3

Step 2: Determine Volume Status Through Clinical Assessment

• Assess for hypovolemia by checking for orthostatic hypotension, dry mucous membranes, decreased skin turgor, flat neck veins, and tachycardia 1, 2
• Assess for hypervolemia by examining for peripheral edema, ascites, jugular venous distention, and pulmonary congestion 1, 2
• Recognize that physical examination alone has limited accuracy (sensitivity 41.1%, specificity 80%) and must be supplemented with laboratory parameters 1
• Consider point-of-care ultrasonography to improve volume status assessment, particularly measuring inferior vena cava diameter and collapsibility 4

Step 3: Obtain Essential Laboratory Tests

• Measure urine osmolality to assess water excretion capacity: <100 mOsm/kg indicates appropriate ADH suppression, while >100 mOsm/kg suggests impaired free water excretion 1, 2
• Measure urine sodium concentration to differentiate causes: <30 mmol/L suggests hypovolemic hyponatremia with extrarenal losses, while >20-40 mmol/L suggests SIADH or renal salt wasting 1, 5
• Check serum creatinine and BUN to assess renal function and identify prerenal azotemia (BUN:creatinine ratio >20:1) 1
• Measure serum uric acid, as levels <4 mg/dL have 73-100% positive predictive value for SIADH 1, 5

Step 4: Exclude Secondary Causes

• Measure thyroid-stimulating hormone (TSH) to rule out hypothyroidism, which can mimic SIADH 1, 5
• Assess adrenal function with morning cortisol or ACTH stimulation test to exclude adrenal insufficiency (cortisol >18-20 µg/dL makes adrenal insufficiency unlikely) 1
• Review all medications for drugs that can cause hyponatremia, including SSRIs, carbamazepine, NSAIDs, opioids, diuretics, and chemotherapy agents 1, 5
• Do NOT routinely measure plasma ADH or natriuretic peptide levels, as these tests are not supported by evidence and delay diagnosis without altering management 1

Step 5: Classify by Volume Status and Urine Studies

Hypovolemic Hyponatremia

• Urine sodium <30 mmol/L indicates extrarenal losses (GI losses, third-spacing, excessive sweating) with 71-100% positive predictive value for saline responsiveness 1, 5
• Urine sodium >20 mmol/L suggests renal losses from diuretics, cerebral salt wasting, or salt-wasting nephropathy 1, 5
• Elevated BUN and creatinine are often present in hypovolemic states 1

Euvolemic Hyponatremia (SIADH)

• Diagnostic criteria require all five features: hypotonic hyponatremia, inappropriately concentrated urine (osmolality >100 mOsm/kg, typically >300 mOsm/kg), elevated urine sodium (>20-40 mEq/L), clinical euvolemia, and normal renal/thyroid/adrenal function 1, 2
• Common causes include malignancies (small cell lung cancer, pancreatic cancer), CNS disorders, pulmonary diseases, and medications 1, 5
• Serum uric acid <4 mg/dL supports SIADH diagnosis but can also occur in cerebral salt wasting 1, 5

Hypervolemic Hyponatremia

• Urine sodium >20 mmol/L reflects compensatory natriuresis despite total body sodium excess 1
• Common causes include cirrhosis with portal hypertension (60% of cirrhotic patients), congestive heart failure, and nephrotic syndrome 1, 5
• Liver function tests and BNP help identify cirrhosis and heart failure as underlying causes 1

Step 6: Special Considerations in Neurosurgical Patients

• Distinguish SIADH from cerebral salt wasting (CSW) as they require opposite treatments: SIADH needs fluid restriction while CSW requires volume and sodium replacement 1
• SIADH characteristics: euvolemic state, urine sodium >20-40 mEq/L, urine osmolality >300 mOsm/kg, central venous pressure 6-10 cm H₂O 1
• CSW characteristics: hypovolemic with orthostatic changes, urine sodium >20 mEq/L despite volume depletion, CVP <6 cm H₂O, evidence of extracellular volume depletion 1
• CSW is more common than SIADH in neurosurgical patients, particularly those with subarachnoid hemorrhage, poor clinical grade, or ruptured anterior communicating artery aneurysms 1

Common Diagnostic Pitfalls to Avoid

• Failing to obtain urine osmolality and urine sodium before initiating therapy can lead to misdiagnosis 1
• Relying solely on physical examination for volume assessment without laboratory correlation may misclassify patients 1
• Ordering ADH levels adds no clinical value and delays diagnosis 1
• Not reviewing medications that can induce SIADH may miss a reversible cause 1
• Omitting exclusion of hypothyroidism and adrenal insufficiency before confirming SIADH can result in incorrect diagnosis 1
• Ignoring mild hyponatremia (130-135 mmol/L) as clinically insignificant, when it increases fall risk (21% vs 5%) and mortality (60-fold increase with sodium <130 mmol/L) 1