How to manage exogenous steroid-induced hyponatremia?

Management of Exogenous Steroid-Induced Hyponatremia

Exogenous steroid-induced hyponatremia is a misnomer—exogenous steroids (prednisolone, dexamethasone, inhaled fluticasone) actually confound the diagnosis of hyponatremia by suppressing cortisol levels, but they do not cause true hyponatremia. 1

Understanding the Clinical Context

The critical issue is distinguishing between:

• Steroid-masked adrenal insufficiency: Exogenous steroids interfere with cortisol measurement, making it appear low when the patient may actually have primary adrenal insufficiency (PAI) causing the hyponatremia 1
• True hyponatremia from other causes: The patient has hyponatremia from SIADH, volume depletion, or other etiologies unrelated to steroid use 2, 3

In primary adrenal insufficiency, hyponatremia occurs in 90% of newly presenting cases due to sodium loss in urine and impaired free water clearance from elevated vasopressin and angiotensin II. 1 Exogenous steroids (oral prednisolone, dexamethasone, or inhaled fluticasone) confound interpretation by suppressing endogenous cortisol production. 1

Diagnostic Approach

Initial Assessment

Measure paired serum cortisol and plasma ACTH to diagnose primary adrenal insufficiency, even if the patient is on exogenous steroids. 1 Key diagnostic thresholds:

• S-cortisol <250 nmol/L with increased ACTH in acute illness is diagnostic of PAI 1
• S-cortisol <400 nmol/L with increased ACTH raises strong suspicion of PAI 1
• In equivocal cases, perform synacthen stimulation test (0.25 mg IM/IV): peak cortisol <500 nmol/L confirms PAI 1

Volume Status Classification

Categorize the patient as hypovolemic, euvolemic, or hypervolemic to guide treatment: 2, 3, 4

• Hypovolemic: Check urine sodium <30 mmol/L (suggests volume depletion) 2
• Euvolemic: Consider SIADH if urine osmolality >100 mOsm/kg with serum osmolality <275 mOsm/kg 2
• Hypervolemic: Assess for heart failure or cirrhosis 2

Management Algorithm

If Primary Adrenal Insufficiency is Confirmed or Suspected

Immediately initiate hydrocortisone 15-25 mg daily in split doses (or cortisone acetate 18.75-31.25 mg) without delaying for diagnostic procedures if acute adrenal crisis is suspected. 1 This addresses the root cause—cortisol deficiency leading to impaired sodium retention and free water clearance. 1

• Hyponatremia will typically resolve with adequate glucocorticoid replacement 1
• Do not treat with sodium supplementation alone, as this addresses the symptom rather than the underlying adrenal insufficiency 5
• Monitor serum sodium during treatment to ensure correction does not exceed 8 mmol/L in 24 hours 2

If Hyponatremia Persists Despite Adequate Steroid Replacement

Treat based on volume status and symptom severity:

For Severe Symptomatic Hyponatremia (seizures, coma, confusion)

• Administer 3% hypertonic saline with goal to correct 6 mmol/L over 6 hours or until symptoms resolve 2, 3, 4
• Maximum correction: 8 mmol/L in 24 hours to prevent osmotic demyelination syndrome 2, 3
• Monitor serum sodium every 2 hours during initial correction 2

For Asymptomatic or Mildly Symptomatic Hyponatremia

Hypovolemic pattern (urine sodium <30 mmol/L):

• Discontinue diuretics 2
• Administer isotonic (0.9%) saline for volume repletion 2

Euvolemic pattern (SIADH suspected):

• Fluid restriction to 1 L/day as first-line treatment 2, 3
• Add oral sodium chloride 100 mEq three times daily if no response to fluid restriction 2

Hypervolemic pattern (heart failure, cirrhosis):

• Fluid restriction to 1-1.5 L/day for sodium <125 mmol/L 2
• Consider albumin infusion in cirrhotic patients 2
• Avoid hypertonic saline unless life-threatening symptoms present 2

Critical Pitfalls to Avoid

• Do not assume exogenous steroids are causing the hyponatremia—they mask the diagnosis of adrenal insufficiency but do not directly cause sodium loss 1, 5
• Never delay treatment of suspected acute adrenal insufficiency for diagnostic testing 1
• Avoid sodium supplementation alone without addressing underlying adrenal insufficiency, as this is ineffective and potentially harmful 5
• Do not correct chronic hyponatremia faster than 8 mmol/L per 24 hours to prevent osmotic demyelination syndrome 2, 3
• In patients with cirrhosis, be aware that trimethoprim/sulfamethoxazole can worsen hyponatremia 6

Monitoring During Treatment

• Check serum sodium every 2-4 hours during active correction 2
• Watch for signs of osmotic demyelination syndrome (dysarthria, dysphagia, oculomotor dysfunction, quadriparesis) typically occurring 2-7 days after rapid correction 2
• If overcorrection occurs (>8 mmol/L in 24 hours), immediately switch to D5W and consider desmopressin 2