Cardiovascular risk profile of low-dose prednisolone and its effect on the quality of life in patients with adrenal insufficiency: the HYPER-AID observational study

Background: Patients with adrenal insufficiency require glucocorticoid replacement therapy either as hydrocortisone in multiple-daily doses or as low-dose prednisolone once daily. Data on the long-term safety, cardiovascular risk, and quality-of-life (QoL) outcomes of prednisolone remain limited. Methods: In this prospective longitudinal cohort study, patients with adrenal insufficiency underwent a pre-specified switch from multiple-daily dose hydrocortisone to once-daily low-dose prednisolone (2-4 mg) as part of routine clinical care and followed up for at least four months. Cardiovascular risk was assessed using anthropometric and biochemical markers (lipid profile, HbA1c, C-reactive protein, blood pressure, and waist and hip circumference). QoL was evaluated using a modified SF-36 questionnaire. Baseline and follow-up measures were compared using paired t-tests or non-parametric equivalents. Results: Of the 62 enrolled patients, 48 completed follow-up. The mean age was 54.5 ± 13 years; 56% were female; and 83% had secondary adrenal insufficiency. After at least four months on prednisolone, weight decreased significantly (90.6-89.6 kg, P = 0.007), accompanied by a reduction in systolic blood pressure (-5 mmHg, P = 0.032). Lipid parameters, HbA1c, and CRP remained unchanged (P > 0.05). Energy scores improved significantly (+9 points, P = 0.003), and patients reported increased treatment convenience (P = 0.002). Conclusion: Low-dose once-daily prednisolone offers comparable cardiovascular risk to hydrocortisone while improving treatment convenience, systolic blood pressure, and SF-36 subjective energy scores. These findings support the use of prednisolone as a potentially preferable alternative in patients with adrenal insufficiency.