Can steroids cause hyponatremia (low sodium levels) in patients, especially those with underlying conditions such as heart failure, liver disease, or a history of electrolyte imbalances?

Can Steroids Cause Hyponatremia?

Steroids themselves do not directly cause hyponatremia; in fact, glucocorticoid deficiency (adrenal insufficiency) is a well-established cause of hyponatremia, and steroid replacement therapy typically corrects it. However, the clinical picture is more nuanced depending on the specific steroid, underlying conditions, and mechanism of action.

Glucocorticoid Deficiency as a Cause of Hyponatremia

The most critical relationship between steroids and hyponatremia is that lack of glucocorticoids causes hyponatremia, not their presence.

• Hyponatremia is present in 90% of newly diagnosed adrenal insufficiency cases and can present with a clinical picture nearly identical to SIADH 1
• Adrenal insufficiency must be excluded before diagnosing SIADH, as both conditions present with euvolemic hypo-osmolar hyponatremia, inappropriately high urine osmolality, and elevated urinary sodium concentration 1
• The standard 0.25 mg cosyntropin stimulation test with cortisol measurements at baseline and 30 minutes post-administration is medically necessary to rule out adrenal insufficiency in patients with hypo-osmolality and hyponatremia 1

Steroid Withdrawal and Hyponatremia

Abrupt discontinuation of chronic corticosteroid therapy can precipitate adrenal crisis with severe hyponatremia due to secondary adrenal insufficiency.

• Patients with a history of chronic corticosteroid use who present with periumbilical abdominal pain, nausea, and electrolyte abnormalities should be evaluated for adrenal crisis 2
• Hypokalemia rather than hyperkalemia may occur when vomiting is present, as aldosterone deficiency is masked by gastrointestinal losses 2
• Treatment should never be delayed for diagnostic procedures if the patient is clinically unstable—give 100 mg IV hydrocortisone immediately plus 0.9% saline infusion 2

Specific Steroid Considerations

Dexamethasone

• Dexamethasone is commonly used in hospitalized patients for its anti-inflammatory effects, and while it can cause hyperglycemia, there is no established association with causing hyponatremia 3
• In patients with suspected adrenal insufficiency who present with hyponatremia, dexamethasone may be part of the treatment rather than the cause 3

Vasopressin (Not a Glucocorticoid)

• Vasopressin, a peptide hormone (not a steroid), can cause hyponatremia through its antidiuretic effects 4
• Overdosage with vasopressin can manifest as hyponatremia due to water retention 4

Clinical Context: Heart Failure and Liver Disease

In patients with heart failure or liver disease, hyponatremia is typically dilutional due to the underlying disease process, not caused by steroids.

• Hyponatremia in heart failure results from increased activity of the sympathetic nervous system, renin-angiotensin-aldosterone system, high levels of arginine vasopressin, and diuretic use 5
• In cirrhosis, hyponatremia is mainly due to systemic and splanchnic vasodilation resulting in decreased effective arterial blood volume, leading to excessive non-osmotic secretion of antidiuretic hormone 6
• Diuretics can cause electrolyte depletion including hyponatremia, particularly when two diuretics are used in combination 7

Critical Pitfalls to Avoid

• Never assume hyponatremia is due to SIADH without first excluding adrenal insufficiency, as both present identically but require opposite treatments—adrenal insufficiency requires glucocorticoid replacement, while SIADH requires fluid restriction 1
• The absence of hyperkalemia cannot rule out adrenal insufficiency, as it is present in only about 50% of cases 1, 2
• In patients on chronic steroids who develop hyponatremia, consider adrenal crisis from steroid withdrawal rather than steroid-induced hyponatremia 2
• When treating concurrent hypothyroidism and adrenal insufficiency, corticosteroids should be started several days before initiating thyroid hormone replacement to prevent precipitating adrenal crisis 1

Treatment Implications

• Correct diagnosis is crucial as treatment approaches differ significantly: adrenal insufficiency requires glucocorticoid replacement therapy, while SIADH requires fluid restriction and possibly vasopressin receptor antagonists 1
• For severe hyponatremia with neurological symptoms, US and European guidelines recommend treating with bolus hypertonic saline to increase serum sodium by 4-6 mEq/L within 1-2 hours but by no more than 10 mEq/L within the first 24 hours to avoid osmotic demyelination 8
• Overly rapid correction of chronic hyponatremia may cause osmotic demyelination syndrome, a rare but severe neurological condition 7, 8