What are the likely causes of severe hyponatremia in an adult patient with no prior medical history?

Causes of Severe Hyponatremia

Severe hyponatremia (serum sodium <125 mmol/L) in an adult with no prior medical history most commonly results from SIADH, medication effects, excessive fluid intake, or acute volume depletion—with SIADH being the single most frequent cause in this population. 1, 2

Classification by Volume Status

The underlying cause must be determined by assessing extracellular fluid volume status, though physical examination alone has poor accuracy (sensitivity 41.1%, specificity 80%) 1:

Hypovolemic Hyponatremia (ECF Depletion)

• Renal losses (urine sodium >20 mmol/L): Diuretic use, salt-wasting nephropathy, cerebral salt wasting, adrenal insufficiency 1, 3
• Extrarenal losses (urine sodium <30 mmol/L): Gastrointestinal losses (vomiting, diarrhea), severe burns, third-space fluid sequestration 1, 3
• Clinical signs include orthostatic hypotension, dry mucous membranes, decreased skin turgor, and flat neck veins 1

Euvolemic Hyponatremia (Normal ECF)

• SIADH is the most common cause, characterized by inappropriate ADH secretion despite low plasma osmolality 1, 2, 4
  • Malignancies (especially small cell lung cancer affecting 1-5% of patients) 1
  • CNS disorders (meningitis, encephalitis, stroke, subarachnoid hemorrhage) 1, 4
  • Pulmonary diseases (pneumonia, tuberculosis) 1, 4
  • Medications: SSRIs, carbamazepine, cyclophosphamide, NSAIDs 1, 5
  • Postoperative states, pain, nausea, stress 1
• Primary polydipsia with excessive free water intake 5
• Hypothyroidism and adrenal insufficiency (must be excluded) 1
• Beer potomania (poor solute intake with excessive beer consumption) 1

Hypervolemic Hyponatremia (Increased ECF with Edema)

• Congestive heart failure with impaired free water excretion 1, 3
• Liver cirrhosis with portal hypertension and ascites (affects ~60% of cirrhotic patients) 1
• Renal disease including nephrotic syndrome and acute/chronic kidney disease 3
• Clinical signs include peripheral edema, ascites, jugular venous distention, and pulmonary congestion 1

Key Diagnostic Features

Laboratory Findings That Distinguish Causes

• Serum osmolality <275 mOsm/kg confirms true hypotonic hyponatremia (excludes pseudohyponatremia and hyperglycemia) 1, 3
• Urine osmolality >100 mOsm/kg indicates impaired water excretion (suggests SIADH or volume depletion) 1
• Urine sodium >20-40 mmol/L with high urine osmolality (>300 mOsm/kg) strongly suggests SIADH 1, 2
• Urine sodium <30 mmol/L predicts saline responsiveness in hypovolemic states (71-100% positive predictive value) 1
• Serum uric acid <4 mg/dL has 73-100% positive predictive value for SIADH 1

Hospital-Acquired Hyponatremia

• Iatrogenic hyponatremia from hypotonic IV fluids in the setting of elevated ADH affects 15-30% of hospitalized patients and is entirely preventable by using isotonic maintenance fluids 1, 2
• Nonosmotic stimuli (pain, nausea, stress, postoperative state) trigger AVP release, impairing free water excretion 1

Critical Causes Not to Miss

Life-Threatening Etiologies Requiring Immediate Recognition

• Acute water intoxication (psychogenic polydipsia, exercise-associated hyponatremia) 5
• Cerebral salt wasting in neurosurgical patients (requires volume replacement, not fluid restriction) 1
• Adrenal crisis (check cortisol and ACTH if suspected) 1
• Severe hypothyroidism (check TSH) 1

Medication-Induced Hyponatremia

Common culprits include diuretics (especially thiazides), SSRIs, carbamazepine, NSAIDs, and cyclophosphamide—these place patients at particularly high risk 1, 5, 4

Clinical Significance and Mortality Risk

Even mild hyponatremia (130-135 mmol/L) should not be ignored, as it increases fall risk (21% vs 5% in normonatremic patients) and mortality 1, 2. Sodium levels <130 mmol/L are associated with a 60-fold increase in hospital mortality (11.2% vs 0.19%) 1. Chronic hyponatremia is also associated with cognitive impairment, gait disturbances, fractures, and bone loss 2, 4.

Common Pitfalls in Diagnosis

• Failing to assess volume status accurately leads to inappropriate treatment 1
• Misdiagnosing SIADH as cerebral salt wasting in neurosurgical patients (they require opposite treatments) 1
• Ignoring mild hyponatremia as clinically insignificant 1
• Not checking for medication causes before pursuing extensive workup 5
• Obtaining ADH and natriuretic peptide levels is not supported by evidence and delays treatment 1