How should I diagnose and treat steroid‑induced hyponatraemia in a patient who recently started or increased a glucocorticoid and now has serum sodium ≤135 mmol/L with mild‑to‑moderate, euvolemic or slightly hypervolemic hyponatraemia after excluding other causes?

Steroid-Induced Hyponatremia: Diagnosis and Management

Immediate Recognition and Empiric Treatment

In a patient with recent glucocorticoid initiation or dose increase who develops euvolemic or mildly hypervolemic hyponatremia (serum sodium ≤135 mmol/L), you must first exclude adrenal insufficiency—particularly if the patient is on exogenous steroids that may have suppressed the hypothalamic-pituitary-adrenal axis—before attributing hyponatremia to other causes. 1

The critical diagnostic challenge is that glucocorticoid deficiency causes hyponatremia through two mechanisms: cortisol deficiency increases vasopressin secretion and impairs free water excretion, while aldosterone deficiency (in primary adrenal insufficiency) causes renal sodium loss. 1 Paradoxically, patients on chronic glucocorticoid therapy who abruptly stop or who have inadequate replacement during stress can develop severe hyponatremia despite their medication history.

Diagnostic Algorithm

Step 1: Assess for Adrenal Insufficiency

Check for clinical signs that mandate immediate empiric hydrocortisone: 1

• Hyperpigmentation (suggests primary adrenal insufficiency)
• Hypotension or orthostatic changes
• Nausea, vomiting, or diarrhea
• Altered mental status or seizures
• History of recent glucocorticoid taper or cessation

Laboratory findings suggestive of adrenal insufficiency: 1

• Hyponatremia present in 90% of newly diagnosed primary adrenal insufficiency
• Urinary sodium >20 mmol/L (often markedly elevated, e.g., 160 mmol/L) despite hyponatremia
• Hypoglycemia
• Hyperkalemia (in primary adrenal insufficiency)
• Elevated serum vasopressin 2

Step 2: Initiate Empiric Hydrocortisone When Indicated

Do not wait for cortisol results if clinical suspicion is high. 1 The European Society of Endocrinology recommends immediate hydrocortisone 100 mg IV bolus, followed by 100-300 mg/day as continuous infusion or divided every 6 hours, plus 1 liter of 0.9% NaCl over one hour. 1

Critical pitfall: "Normal" cortisol levels can be inappropriately low in acute illness—a cortisol <250 nmol/L (<9 μg/dL) during severe stress suggests relative adrenal insufficiency. 1

Step 3: Distinguish from SIADH

Glucocorticoids can mask SIADH by suppressing ADH secretion. 3 If a patient's hyponatremia improves with glucocorticoid therapy but recurs when steroids are stopped or switched to oral administration, consider SIADH as the underlying diagnosis. 3

Key differentiating features: 4, 1

• Adrenal insufficiency: Hypovolemic or euvolemic, urinary sodium often >20 mmol/L (can be very high), responds to hydrocortisone without sodium supplementation
• SIADH: Euvolemic, urinary sodium >20-40 mmol/L, urine osmolality >300 mOsm/kg, requires fluid restriction as primary therapy

Sodium Correction Strategy

In Adrenal Insufficiency

Hyponatremia in adrenal insufficiency often does not respond to sodium supplementation alone but requires glucocorticoid replacement. 1 The mechanism is redistribution of sodium from serum to cells/interstitium, not absolute sodium deficiency. 5

After initiating hydrocortisone: 1, 6

• Monitor serum sodium every 2 hours initially in severe cases
• Maximum correction rate: 8 mmol/L in 24 hours to prevent osmotic demyelination syndrome
• In patients with central adrenal insufficiency (especially if concurrent central diabetes insipidus is possible), use incremental increases in glucocorticoid doses to reduce ODS risk 6

Special Consideration: Preventing Overcorrection

Patients with adrenal insufficiency are at exceptionally high risk for osmotic demyelination syndrome because glucocorticoid replacement can cause rapid sodium correction. 6 Start with hydrocortisone 50-100 mg IV and gradually increase to maintenance doses (15-25 mg daily in divided doses) over 48-72 hours. 1, 6

If sodium rises >8 mmol/L in 24 hours, immediately discontinue current fluids, switch to D5W, and consider desmopressin to slow the rise. 4

Treatment Protocol

Initial Management (First 24-48 Hours)

1. Hydrocortisone 100 mg IV bolus if adrenal insufficiency suspected 1
2. Isotonic saline (0.9% NaCl) 1 liter over 1 hour for volume repletion 1
3. Monitor serum sodium every 2 hours during acute correction 1
4. Target correction: 4-6 mmol/L in first 24 hours (maximum 8 mmol/L) 1, 6

Maintenance Phase (After 48-72 Hours)

1. Taper to oral hydrocortisone 15-25 mg daily in divided doses (typically 10 mg morning, 5 mg afternoon, 5 mg evening) 1
2. Switch to isotonic maintenance fluids at 30 mL/kg/day 4
3. Monitor sodium every 4-6 hours until stable 4
4. Watch for signs of osmotic demyelination syndrome (dysarthria, dysphagia, oculomotor dysfunction, quadriparesis) 2-7 days after correction 4

Common Pitfalls and How to Avoid Them

Pitfall 1: Waiting for cortisol results before treating suspected adrenal crisis. 1 Treatment should never be delayed by diagnostic procedures in acute adrenal insufficiency. 7

Pitfall 2: Giving only sodium supplementation without glucocorticoids. 1, 5 Hyponatremia in adrenal insufficiency reflects sodium redistribution, not absolute deficiency, and will not respond to saline alone.

Pitfall 3: Assuming glucocorticoid therapy excludes adrenal insufficiency. 3 Patients on chronic steroids can develop relative adrenal insufficiency during stress or after dose reduction.

Pitfall 4: Correcting sodium too rapidly after starting hydrocortisone. 6 Glucocorticoid replacement can cause rapid sodium correction—use incremental dose increases and frequent monitoring.

Pitfall 5: Misdiagnosing SIADH as adrenal insufficiency. 3 If hyponatremia improves with glucocorticoids but recurs when stopped, reassess for SIADH and implement fluid restriction.

When to Consider Alternative Diagnoses

If hyponatremia persists despite adequate glucocorticoid replacement (48-72 hours of hydrocortisone 100-300 mg/day), reassess for: 4, 3

• SIADH (treat with fluid restriction to 1 L/day)
• Cerebral salt wasting (treat with volume and sodium replacement, not fluid restriction)
• Hypervolemic hyponatremia from heart failure or cirrhosis (treat with fluid restriction to 1-1.5 L/day)

Volume status assessment is critical: 4

• Hypovolemic signs: orthostatic hypotension, dry mucous membranes, flat neck veins → volume repletion
• Euvolemic: no edema, normal skin turgor → consider SIADH or adrenal insufficiency
• Hypervolemic: peripheral edema, ascites, JVD → fluid restriction