Glucocorticoids Cause Hypokalemia, Not Hyperkalemia
Glucocorticoids consistently cause hypokalemia through multiple mechanisms including enhanced renal potassium excretion, transcellular potassium shifts, and stimulation of Na⁺-K⁺ ATPase activity. This is the opposite effect of mineralocorticoid receptor antagonists, which cause hyperkalemia by blocking aldosterone's potassium-excreting effects 1.
Mechanisms of Glucocorticoid-Induced Hypokalemia
Glucocorticoids lower serum potassium through several pathways:
Enhanced renal potassium excretion: Glucocorticoids stimulate renal hydrogen ion secretion and increase potassium clearance, though this effect is less pronounced than with mineralocorticoids like deoxycorticosterone 2.
Transcellular potassium shift: Glucocorticoids stimulate Na⁺-K⁺ ATPase activity (mediated by insulin and amylin), driving potassium from extracellular to intracellular compartments 3.
Insulin resistance and hyperglycemia: Glucocorticoids cause insulin resistance leading to hyperglycemia, which further promotes intracellular potassium shifts 3.
Dexamethasone specifically promotes potassium excretion and lowers serum potassium levels, contrasting sharply with mineralocorticoid receptor antagonists that cause hyperkalemia 1.
Clinical Evidence and Incidence
The risk of hypokalemia with glucocorticoids is well-documented:
In hospitalized patients receiving potassium-losing diuretics, concurrent glucocorticoid administration (prednisone 5-2,000 mg/day) was a significant independent risk factor for hypokalemic events 4.
Glucocorticoids can trigger hypokalemic paralysis, even after single-dose or short-term administration, particularly in patients with underlying periodic paralysis disorders 3.
A recent case documented hypokalemic paralysis in an adolescent following intramuscular dexamethasone and vitamin B12 injection, requiring potassium replacement therapy for full recovery 5.
Critical Clinical Distinction
Do not confuse glucocorticoids with mineralocorticoid excess syndromes:
Mineralocorticoid excess (primary hyperaldosteronism, Cushing's syndrome with severe hypercortisolism) causes hypertension with hypokalemia and metabolic alkalosis 6, 7.
Mineralocorticoid receptor antagonists (spironolactone, eplerenone) cause hyperkalemia by blocking aldosterone, with incidence ranging from 2-5% in trials to 24-36% in population registries 1.
Pure glucocorticoids (dexamethasone, triamcinolone, prednisone) cause hypokalemia without the sodium retention and hypertension typical of mineralocorticoids 2.
Monitoring Recommendations
When prescribing glucocorticoids, particularly in combination therapy:
Monitor serum potassium levels in at-risk patients, especially those on diuretics or with baseline electrolyte abnormalities 5, 4.
Glucocorticoid-induced hypokalemia is dose-dependent, with higher doses (>20 mg prednisone equivalent daily) carrying greater risk 4.
Patients receiving >12 medications concurrently have significantly increased risk of developing hypokalemia 4.
Female sex is a minor additional risk factor for glucocorticoid-induced hypokalemia 4.
Important Caveats
In severe hypercortisolism (Cushing's syndrome), the combination of hypokalemia and hyponatremia indicates severe disease requiring urgent intervention 7. This represents excessive cortisol with mineralocorticoid activity overwhelming renal capacity, not the typical effect of therapeutic glucocorticoid administration.
Glucocorticoids should be administered with caution in patients with periodic paralysis, as they can trigger acute paralytic attacks through rapid potassium shifts 3.