Adrenal Insufficiency Risk with Long-Term Low-Dose Prednisolone
Yes, long-term prednisolone can cause adrenal insufficiency even at low doses of 5 mg per day or greater when administered for one month or more. 1
Mechanism and Risk Factors
- Prednisolone and other glucocorticoids can cause suppression of the hypothalamic-pituitary-adrenal (HPA) axis, leading to secondary adrenal insufficiency 1
- Daily doses of prednisolone ≥5 mg in adults administered for ≥1 month may result in HPA axis suppression 1
- This risk applies across all routes of administration (oral, inhaled, topical, intranasal, intra-articular) 1
- The prevalence of adrenal insufficiency in patients on long-term low-dose prednisolone (5 mg/day) is high - affecting approximately 39-48% of patients 2
Evidence from Clinical Studies
- A cross-sectional study of 42 rheumatoid arthritis patients on 5 mg prednisolone daily for ≥6 months found that 48% had insufficient adrenal response to Synacthen testing 2
- Even when excluding patients who had received other glucocorticoid formulations within the previous 3 months, 39% still showed adrenal insufficiency 2
- The duration of treatment did not correlate with the severity of adrenal suppression, suggesting that even short-term use at low doses can cause HPA axis suppression 2
Clinical Implications
- Patients on chronic prednisolone therapy are at risk of adrenal crisis during times of physiological stress (surgery, illness) 1
- Adrenal insufficiency can persist even after glucocorticoid withdrawal - one case report documented adrenal insufficiency occurring 4 years after prednisolone withdrawal 3
- The FDA drug label for prednisolone explicitly states that adrenal insufficiency is a known adverse effect of prolonged use 4
- Mortality is increased in patients with adrenal insufficiency, with risk ratios of 2.19 for men and 2.86 for women 1
Management Considerations
- Patients on long-term prednisolone should not stop therapy abruptly due to risk of adrenal crisis 1
- Stress-dose steroids are required during periods of physiological stress (surgery, illness) for patients on chronic prednisolone therapy 1
- For patients with suspected adrenal insufficiency due to prednisolone use, hydrocortisone replacement may be needed, with gradual tapering to allow endogenous adrenal function to recover 5
- Patients should be educated about the risk of adrenal insufficiency, how to prevent adrenal crisis, and when to seek medical attention 1
Common Pitfalls and Caveats
- Adrenal insufficiency may be missed as a diagnosis because symptoms can be nonspecific (fatigue, nausea, hypotension) 5
- Alternate-day prednisolone dosing does not eliminate the risk of adrenal suppression 1
- Testing for adrenal function should not be performed while patients are still taking prednisolone, as this can give false results 1
- Patients may be taking over-the-counter or prescribed glucocorticoids from multiple sources (topical, inhaled, etc.), which can have additive effects on adrenal suppression 1
In conclusion, healthcare providers should be vigilant about the risk of adrenal insufficiency in all patients on long-term prednisolone therapy, even at doses as low as 5 mg daily, and should take appropriate precautions during periods of physiological stress.