What could be the cause of my polyuria with normal electrolyte panel results, including serum sodium level at the lower end of the normal range, normal glucose, normal calcium, and normal potassium levels?

Differential Diagnosis of Polyuria with Normal Electrolytes

Your normal electrolyte panel does not rule out diabetes insipidus or other causes of polyuria—you need urine osmolality measurement and possibly serum osmolality to determine the underlying cause. 1

Immediate Diagnostic Steps Required

Measure urine osmolality as the critical first test to distinguish between water diuresis (dilute urine) and solute diuresis (concentrated urine). 2

• Urine osmolality <150 mOsm/L indicates water diuresis (diabetes insipidus or primary polydipsia) 2
• Urine osmolality >300 mOsm/L indicates solute diuresis (osmotic diuresis from glucose, urea, or sodium) 2
• Urine osmolality 150-300 mOsm/L suggests mixed mechanisms 2

Simultaneously measure serum osmolality with urine osmolality. The combination of inappropriately diluted urine (<200 mOsm/kg H₂O) with high-normal or elevated serum sodium is pathognomonic for diabetes insipidus. 1

Why Your Normal Labs Don't Exclude Important Diagnoses

Your serum sodium of 140 mEq/L sits at the lower end of normal range (135-145 mEq/L), which can occur in early or partial diabetes insipidus where patients compensate by drinking enough water. 3, 1

Normal serum osmolality does not rule out diabetes insipidus—certain clinical scenarios can present with normal osmolality despite the diagnosis, particularly when patients maintain adequate fluid intake. 1

Normal glucose (90 mg/dL) makes uncontrolled diabetes mellitus unlikely, though glucose-induced osmotic diuresis typically presents with plasma glucose >250 mg/dL and urine glucose concentrations of 300-400 mmol/L. 3, 4

Primary Diagnostic Considerations

Water Diuresis (If Urine Osmolality <150 mOsm/L)

Central diabetes insipidus should be suspected if copeptin plasma levels are low or absent, indicating inadequate ADH secretion. 1

• Obtain MRI of the sella turcica with contrast using high-resolution pituitary protocols to evaluate for masses or infiltrative processes affecting the hypothalamic-neurohypophyseal axis 1
• Look for loss of the normal posterior pituitary bright spot on T1-weighted sequences 1

Nephrogenic diabetes insipidus is confirmed by elevated copeptin levels (indicating high ADH but renal resistance). 1

• Consider genetic testing, as ~90% of cases are X-linked (AVPR2 mutations) and <10% are autosomal (AQP2 mutations) 1
• Perform renal ultrasound to assess for urinary tract dilation from chronic polyuria 1

Primary polydipsia presents with similar urine dilution but normal ADH response during water deprivation testing. 2

Solute Diuresis (If Urine Osmolality >300 mOsm/L)

Calculate 24-hour urinary osmole excretion to identify excessive solute load. 5

• High protein intake or post-obstructive diuresis can cause solute-induced polyuria 5
• Measure urine sodium, potassium, and urea to identify the predominant osmole 2

Chronic kidney disease with impaired concentrating ability can present with polyuria despite normal serum creatinine in early stages. 6

Critical Pitfall to Avoid

Do not assume normal electrolytes exclude significant pathology. Volume depletion from gastrointestinal or renal sodium losses presents with normal or low plasma osmolality, not elevated sodium. 3, 1 Your presentation suggests water diuresis rather than volume depletion, but this distinction requires urine osmolality measurement.

Next Steps Algorithm

1. Measure urine osmolality and serum osmolality simultaneously 1, 2
2. If urine osmolality <150 mOsm/L: Measure copeptin levels to distinguish central from nephrogenic diabetes insipidus, or proceed with water deprivation test if copeptin unavailable 1
3. If urine osmolality >300 mOsm/L: Calculate 24-hour urinary osmole excretion and measure urine electrolytes to identify solute source 2, 5
4. If central diabetes insipidus confirmed: Obtain pituitary MRI and consider desmopressin trial 1
5. If nephrogenic diabetes insipidus confirmed: Initiate thiazide diuretics plus NSAIDs, implement low-salt diet (≤6 g/day), and restrict protein (<1 g/kg/day) 1