Endocrine Abstracts

JOINT3426

Background: Current Endocrine Society guidelines recommend thrice-daily hydrocortisone for the management of adrenal insufficiency. Prednisolone is suggested as a second-line treatment but previous studies have evaluated its use at greater than 5 mg. We have safely used low-dose prednisolone (2–4 mg) for over 10 years, culminating in this study to address the current vacuum of evidence.

Methods: Patients with adrenal insufficiency were recruited to this double-blind, randomised crossover study. Participants received 4 months of low-dose prednisolone (2–4 mg) with matching placebo at noon and in the afternoon, or 4 months of standard regimen hydrocortisone (10 / 5 / 2.5 mg). They were then crossed over to the alternative medication for the second study period. Observations (including weight, waist–hip circumference, blood pressure), biochemical data for cardiometabolic health and bone turnover, and subjective health data (SF-36 and Addisons Quality of Life (Addi-QoL)) were collected. Baseline and end-point data were collected at days 1, 30 and 120 of each study period, on both medications.

Results: A significant treatment difference of −1.87 Kg (P=0.002) in weight was detected in association with prednisolone treatment. There were further significant reductions in waist circumference and HbA1c of −2.26 cm (P=0.010) and −1.23 mmol/mol (P=0.001). Bone formation markers were suppressed on prednisolone with a treatment difference of −1.22 μg/l (P=0.035) in osteocalcin levels and −13.8 ng/l (P<0.001) in Procollagen 1 N-Terminal Propeptide. Bone resorption was also suppressed with Urinary N-telopeptide levels, decreasing by −9.34 nmol/mmol (P=0.002) with prednisolone. There was no significant difference in blood pressure, high-sensitivity troponin and CRP, between the treatments. Data from SF-36 survey and Addi-QoL questionnaire demonstrated that subjective health outcomes were unaffected by both hydrocortisone and prednisolone.

Discussion: We demonstrate evidence that low-dose prednisolone is associated with weight loss and reductions in HbA1c, suggesting superior cardiovascular outcomes compared to standard hydrocortisone treatment. This study is limited by the use of short-term markers, but is an important stepping-stone in normalising the use of prednisolone in adrenal insufficiency. Importantly, there were no adverse effects on wellbeing. These results could be explained by the reduced steroid exposure seen with low-dose prednisolone treatment. Alternatively, once-daily dosing may mimic the normal diurnal rhythm of physiological cortisol secretion better than thrice-daily hydrocortisone.

Conclusion: Once-daily low-dose prednisolone is an alternative to standard-regimen hydrocortisone. Further studies should be completed using low-dose prednisolone, focussing on longer term outcomes such as bone-mineral density and real-world mortality.