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 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 (2-4mg) as part of routine clinical care and followed for at least four months. Cardiovascular risk was assessed using anthropometric and biochemical markers (lipid profile, HbA1c, C-reactive protein, blood pressure, 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. Mean age was 54.5 ± 13 years; 56% were female; 83% had secondary adrenal insufficiency. After at least four months on prednisolone, weight decreased significantly (90.6 kg to 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 its use as a potentially preferable alternative in patients with adrenal insufficiency.