Can long-term intake of steroids, such as prednisone (corticosteroid), lead to mineralocorticosteroid deficiency in patients with a history of chronic inflammatory diseases like rheumatoid arthritis or asthma?

Long-Term Steroid Use and Mineralocorticoid Deficiency

Long-term steroid intake, particularly with glucocorticoids like prednisone, does not cause mineralocorticoid deficiency but rather causes secondary adrenal insufficiency through suppression of the hypothalamic-pituitary-adrenal (HPA) axis, which may impair mineralocorticoid secretion as a consequence of overall adrenal suppression. 1

Mechanism of Adrenal Suppression

• Glucocorticoid therapy suppresses the HPA axis, leading to secondary (central) adrenal insufficiency rather than primary adrenal failure 2, 1
• The FDA label for prednisone explicitly states that "drug-induced secondary adrenocortical insufficiency may be minimized by gradual reduction of dosage" and notes that "since mineralocorticoid secretion may be impaired, salt and/or a mineralocorticoid should be administered concurrently" 1
• HPA axis suppression should be anticipated in any patient receiving more than 7.5 mg of prednisolone equivalent daily for more than 3 weeks 3
• This type of relative insufficiency may persist for up to 12 months after discontinuation of therapy following large doses for prolonged periods 1

Clinical Manifestations of Steroid-Induced Adrenal Insufficiency

• Symptoms include fatigue, weakness, anorexia, nausea, vomiting, abdominal pain, hypotension, and electrolyte abnormalities 2
• The distinction between primary and secondary adrenal insufficiency can be made by measuring ACTH and cortisol levels—if ACTH is low with low cortisol, this indicates secondary (central) adrenal insufficiency 4
• In secondary adrenal insufficiency from chronic steroid use, mineralocorticoid function is typically preserved because aldosterone secretion is primarily regulated by the renin-angiotensin system rather than ACTH 4

When Mineralocorticoid Replacement May Be Needed

• The FDA label notes that "since mineralocorticoid secretion may be impaired, salt and/or a mineralocorticoid should be administered concurrently" during stress situations in patients with steroid-induced adrenal insufficiency 1
• For primary adrenal insufficiency (not typical with exogenous steroid use), fludrocortisone starting dose of 0.05-0.1 mg/day is recommended, adjusted based on volume status, sodium level, and renin response 4
• Most cases of steroid-induced adrenal insufficiency do not require mineralocorticoid replacement because aldosterone production remains intact 4

Risk Factors and Duration

• Prolonged corticosteroid use (more than 3 months) causes numerous complications including HPA axis suppression 4, 5
• The risk increases with higher doses and longer duration of therapy 1
• In inflammatory bowel disease, prolonged steroid use (more than 3000 mg prednisolone equivalent in 1 year) carries greater mortality 4

Diagnostic Approach

• The standard diagnostic test is the 0.25 mg cosyntropin (ACTH) stimulation test with cortisol measurements at baseline and 30 minutes post-administration; a peak cortisol value below 500 nmol/L is diagnostic of adrenal insufficiency 2
• Morning cortisol levels below 6.2 µg/dL indicate adrenal suppression 4
• Monitoring of adrenal gland suppression should be considered in patients on long-term topical or systemic steroid therapy, especially children receiving steroids for multiple conditions 4

Prevention and Management

• Patients on long-term steroids require education about stress dosing, emergency injectables, when to seek medical attention for impending adrenal crisis, and should wear a medical alert bracelet or necklace for adrenal insufficiency 4
• In stress situations (surgery, acute illness), hormone therapy should be reinstituted or increased 1
• For unexplained hypotension during surgery unresponsive to fluids, adrenal insufficiency should be considered and 100 mg IV hydrocortisone should be administered 2

Common Pitfall to Avoid

The critical error is confusing secondary adrenal insufficiency (which affects primarily cortisol production) with primary adrenal insufficiency (Addison's disease, which affects both cortisol and aldosterone). Long-term exogenous steroid use causes secondary adrenal insufficiency through HPA axis suppression, not primary adrenal failure. Therefore, mineralocorticoid deficiency is not the primary concern—glucocorticoid replacement during stress and gradual tapering to allow HPA axis recovery are the key management priorities. 1, 4