How should hyponatremia that develops in a patient receiving or recently stopped systemic corticosteroids be evaluated and managed, considering possible secondary adrenal insufficiency?

Hyponatremia Secondary to Corticosteroids: Evaluation and Management

Hyponatremia developing in a patient receiving or recently stopping systemic corticosteroids should be immediately evaluated for secondary adrenal insufficiency, as this represents a potentially life-threatening condition that requires urgent glucocorticoid replacement rather than sodium supplementation alone. 1, 2

Immediate Clinical Assessment

When hyponatremia occurs in the context of corticosteroid use or recent discontinuation, you must first determine clinical stability:

• If the patient is unstable (hypotension, altered mental status, severe vomiting, or shock): Give 100 mg IV hydrocortisone immediately and infuse 0.9% saline at 1 L/hour without waiting for diagnostic testing 1, 3, 4
• Never delay treatment for diagnostic procedures in suspected adrenal crisis—mortality is high if untreated 1, 2, 3

Understanding the Mechanism

The hyponatremia in corticosteroid-related adrenal insufficiency is not primarily due to sodium deficiency but rather to sodium and water redistribution from serum to cells and interstitial spaces due to insufficient cortisol 5. This explains why sodium supplementation alone is often ineffective and sometimes catastrophic 5. Additionally, insufficient cortisol fails to suppress antidiuretic hormone (ADH) during stress, leading to inappropriate water retention 6, 7.

Key Distinguishing Features from SIADH

Critical pitfall: Adrenal insufficiency can present identically to SIADH with euvolemic hypo-osmolar hyponatremia, and must be excluded before diagnosing SIADH 1. Both conditions show:

• Serum sodium <134 mEq/L
• Plasma osmolality <275 mOsm/kg
• Inappropriately high urine osmolality
• Elevated urinary sodium 1

However, secondary adrenal insufficiency from corticosteroids has specific features:

• Absence of hyperkalemia (aldosterone function is preserved in secondary AI, unlike primary AI) 2, 4
• Absence of hyperpigmentation (no elevated ACTH to stimulate melanocytes) 2, 4
• Hyponatremia is present in 90% of newly diagnosed adrenal insufficiency cases 1, 2, 3
• Morning nausea, lack of appetite, and unexplained fatigue are particularly common 2

Diagnostic Workup for Stable Patients

If the patient is stable enough for testing:

Initial Laboratory Tests

1. Draw morning (8 AM) cortisol and ACTH before any steroid administration 1, 3, 4

   • Cortisol <250 nmol/L (<9 µg/dL) with low/normal ACTH confirms secondary adrenal insufficiency 1, 3
   • Cortisol 140-275 nmol/L (5-10 µg/dL) with low or inappropriately normal ACTH is indicative of secondary AI 1, 4
   • Cortisol <400 nmol/L with clinical instability warrants empiric treatment 3

2. Basic metabolic panel to assess sodium, potassium, and glucose 1

Confirmatory Testing

Cosyntropin stimulation test is the gold standard when initial cortisol is indeterminate 1, 3:

• Administer 0.25 mg (250 mcg) cosyntropin IV or IM 1, 3, 4
• Measure serum cortisol at baseline, 30 minutes, and 60 minutes 1
• Peak cortisol <500 nmol/L (<18 µg/dL) is diagnostic of adrenal insufficiency 1, 3, 4
• Peak cortisol >550 nmol/L (>18-20 µg/dL) excludes adrenal insufficiency 1

Critical Testing Pitfalls to Avoid

• Do not attempt diagnostic testing while the patient is still on corticosteroids—exogenous steroids (including prednisone, dexamethasone, and inhaled fluticasone) suppress the HPA axis and cause false-positive results 1, 2
• Morning cortisol measurements in patients actively taking corticosteroids are not diagnostic because assays measure both endogenous cortisol and therapeutic steroids 1
• If you must treat before confirming diagnosis, use dexamethasone 4 mg IV instead of hydrocortisone, as dexamethasone does not interfere with cortisol assays 1

Management Based on Severity

Acute/Severe Presentation (Adrenal Crisis)

• Hydrocortisone 100 mg IV bolus immediately 1, 3, 4
• 0.9% saline infusion at 1 L/hour (at least 2L total) 1, 3
• Continue hydrocortisone 200 mg/24 hours as continuous infusion or 50 mg IV every 6 hours 6
• Taper to maintenance dosing over 2-3 days once stable 3

Moderate Symptoms (Stable but Symptomatic)

• Initiate outpatient treatment at 2-3 times maintenance dose 1
• Hydrocortisone 30-50 mg total daily or prednisone 20 mg daily 1
• Taper to maintenance over several days as symptoms improve 1

Maintenance Therapy

Once diagnosis is confirmed and patient is stable:

• Hydrocortisone 15-25 mg daily in divided doses (typically 10 mg at 7 AM, 5 mg at noon, 2.5-5 mg at 4 PM) 1, 4
• Alternative: Prednisone 3-5 mg daily 1, 4
• Fludrocortisone is NOT needed for secondary adrenal insufficiency (aldosterone function is intact) 4

Duration of Treatment and HPA Axis Recovery

Important consideration: Patients who received corticosteroids >14 days are particularly likely to have prolonged HPA axis suppression and may require:

• Gradual taper rather than abrupt discontinuation 6
• Evaluation of HPA axis function if in doubt 6
• Testing for HPA axis recovery after 3 months of maintenance therapy 1
• Some patients may require lifelong replacement if the HPA axis does not recover 3

Patient Education and Long-Term Management

All patients with confirmed adrenal insufficiency require:

• Education on stress dosing (double or triple dose during illness, fever, or physical stress) 1, 4
• Medical alert bracelet indicating adrenal insufficiency 1, 4
• Emergency injectable hydrocortisone 100 mg IM kit with self-injection training 1, 4
• Mandatory endocrine consultation for newly diagnosed cases, pre-operative planning, and recurrent crises 1

Monitoring After Corticosteroid Discontinuation

Critical monitoring period: Inflammation may recur after discontinuing corticosteroid therapy, especially when stopped abruptly 6. Watch for:

• Development of shock or need for mechanical ventilation 6
• Recurrence of symptoms (nausea, hypotension, fatigue) 6
• Signs of adrenal insufficiency including orthostatic hypotension 6
• Persistent pyrexia (may be due to adrenal insufficiency, not just infection) 6

If deterioration occurs after stopping corticosteroids, reinitiating corticosteroid therapy should be strongly considered 6.