Can systemic corticosteroids cause serum electrolyte imbalances?

Systemic Corticosteroids Cause Serum Electrolyte Imbalances

Yes, systemic corticosteroids definitively cause serum electrolyte imbalances through multiple mechanisms, including sodium retention, potassium loss, and alterations in calcium handling. 1

Primary Electrolyte Disturbances

Sodium retention and hypokalemic alkalosis are the hallmark electrolyte abnormalities of corticosteroid therapy. The FDA drug label for methylprednisolone explicitly lists sodium retention, fluid retention, potassium loss, and hypokalemic alkalosis as adverse reactions. 1

Sodium and Water Homeostasis

• Corticosteroids increase serum sodium concentration by 1.67–2.61 mmol/L in stable outpatients, with the effect occurring regardless of dose or duration of therapy. 2
• Sodium retention occurs through overstimulation of the mineralocorticoid receptor (MR) in the kidney, leading to volume expansion and hypertension. 3
• At high physiological cortisol levels, the protective enzyme 11β-hydroxysteroid dehydrogenase type 2 (11βHSD2) becomes saturated, allowing glucocorticoids to activate the MR despite its intended selectivity for aldosterone. 3

Potassium Depletion

• Potassium loss and hypokalemic alkalosis are direct consequences of corticosteroid therapy, as documented in the FDA label. 1
• Hypokalaemia or hypomagnesaemia can promote toxic colonic dilatation in patients with severe ulcerative colitis, making potassium supplementation of at least 60 mmol/day necessary during acute severe colitis treated with IV corticosteroids. 4
• The effect on potassium is dose-dependent and biphasic: low-dose corticosterone (10⁻⁹ M) increases potassium secretion, while higher doses (10⁻⁷ M) promote potassium absorption. 5

Calcium Metabolism

• Corticosteroids induce sustained renal calcium excretion, contributing to osteoporosis through both decreased intestinal calcium absorption and increased urinary calcium loss. 3

Clinical Contexts Requiring Monitoring

Severe Ulcerative Colitis

• IV fluid and electrolyte replacement to correct and prevent dehydration and electrolyte imbalance is essential when treating acute severe colitis with intravenous corticosteroids. 4
• Potassium supplementation of at least 60 mmol/day is usually necessary during IV steroid therapy for severe colitis. 4
• Electrolyte abnormalities and anemia should be corrected if needed in all patients receiving IV steroids for severe active ulcerative colitis. 4

Immunotherapy-Related Toxicity

• Patients with diarrhea on anti-CTLA4 therapy should undergo workup including serum electrolyte profile before initiating systemic corticosteroids. 4
• Autoimmune nephropathy presenting as electrolyte imbalance may occur during immuno-oncological therapy, requiring corticosteroid treatment that itself can further affect electrolyte balance. 6
• Endocrine and metabolic disorders such as adrenal insufficiency and hypothyroidism should be excluded as possible causes of electrolyte abnormalities before attributing them solely to immunotherapy or its corticosteroid treatment. 6

Peptide Receptor Radionuclide Therapy

• Hyperosmotic amino acid solutions used during PRRNT can induce dangerous electrolyte imbalances (hyperkalaemia and hypernatraemia) leading to severe metabolic acidosis and cardiac arrhythmias. 4
• Corticosteroids (e.g., dexamethasone) are administered as antiemetics during amino acid infusion, potentially compounding electrolyte disturbances. 4
• Particular attention and care should be given to avoiding possible electrolyte imbalance, with management by hydrating the patient with normal saline and possibly repeating corticosteroid or antiemetic administrations. 4

Perioperative and Critical Care

• Glucocorticoid therapy in hospitalized patients (prevalence approaching 10%) can induce hyperglycemia and electrolyte disturbances in patients with and without antecedent diabetes. 4
• Monitor blood glucose at least every 2–4 hours while patient is taking nothing by mouth during perioperative glucocorticoid therapy. 4

Mechanisms of Action

• Corticosteroids exert regulatory control of colonic fluid and electrolyte function, with the native glucocorticoid corticosterone showing dose-related stimulatory effects on sodium and fluid transfer. 5
• The adrenal cortex is an important factor in the control of electrolyte and water balance and blood pressure homeostasis, with hypersecretion associated with hypertension, sodium retention, potassium wastage, and metabolic alkalosis. 7

Critical Monitoring Parameters

• Serum electrolytes (sodium, potassium, magnesium) should be monitored regularly in all patients on systemic corticosteroid therapy, particularly those receiving IV steroids or high doses. 4, 1
• Electrolyte disturbances may develop gradually alongside oliguria, anuria, and swelling in patients with corticosteroid-related renal toxicity. 6
• The prognosis is generally favorable because electrolyte abnormalities respond well to corticosteroid dose adjustment and supportive care. 6