Once-Daily Low-Dose Prednisolone Improves Cardiometabolic Profiles in Adrenal Insufficiency Versus Multiple-Daily Dose Hydrocortisone in a Double-Blind Randomised Crossover Trial

Sirazum Choudhury; Katharine Lazarus; Angelica Sharma; Kavita Narula; Cara Go; Suzie Cro; Thilipan Thaventhiran; Bernard Khoo; Tricia Tan; Karim Meeran

doi:10.1530/endoabs.117.P8

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Endocrine Abstracts (2026) 117 P8 | DOI: 10.1530/endoabs.117.P8

SFEBES2026 Poster Presentations Adrenal and Cardiovascular (54 abstracts)

Once-Daily Low-Dose Prednisolone Improves Cardiometabolic Profiles in Adrenal Insufficiency Versus Multiple-Daily Dose Hydrocortisone in a Double-Blind Randomised Crossover Trial

Sirazum Choudhury ^1,2,3 , Katharine Lazarus ^1,2 , Angelica Sharma ^1,2 , Kavita Narula ^1,2 , Cara Go ² , Suzie Cro ² , Thilipan Thaventhiran ^1,2 , Bernard Khoo ⁴ , Tricia Tan ^1,2,3 & Karim Meeran ^1,2

Author affiliations

¹Imperial College Healthcare NHS Trust, London, United Kingdom; ²Imperial College London, London, United Kingdom; ³North West London Pathology, London, United Kingdom; ⁴University College London, London, United Kingdom

Background: Once-daily low-dose prednisolone and multiple-daily dose hydrocortisone are options for management of adrenal insufficiency (AI). This is the first double-blind trial comparing these two treatments.

Methods: This is a double-blind randomised crossover study. Patients with AI 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) in the first study period. They were then crossed over to the alternative medication for the second study period. Anthropometrics, biochemical data for cardiometabolic and bone health, and subjective health survey data were collected at Day 1, 30 and 120 of each study period.

Results: There was a significant reduction in body weight at 4 months, with a treatment difference of -1.87 Kg (P = 0.002) favouring prednisolone treatment. Waist circumference and HbA1c reduced by -2.26 cm (P = 0.010) and -1.23 mmol/mol (P = 0.001) on prednisolone. Short-term and medium-term bone formation markers were suppressed on prednisolone with a treatment difference of -1.22 µg/l (P = 0.035) in osteocalcin and -13.8 ng/l (P < 0.001) in Procollagen 1 N-Terminal Propeptide. Urinary N-telopeptide levels, a resorption marker was also suppressed by -9.34 nmol/mmol (P = 0.002), associated with prednisolone. Other cardiovascular markers such as blood pressure, high-sensitivity troponin and CRP, did not show significant differences between prednisolone and hydrocortisone. Data from SF-36 survey and Addi-QoL questionnaire demonstrated that subjective health outcomes were unaffected by either medication.

Discussion: Once-daily low-dose prednisolone causes weight loss and HbA1c improvement, without compromising wellbeing. This may be because hydrocortisone is associated with uncoupling from the normal physiological profile of cortisol, or multiple-daily doses causing increased steroid exposure.

Conclusion: This study supports the routine use of low dose prednisolone. Further studies should be completed using low-dose prednisolone, focussing on longer term outcomes such as bone-mineral density and real-world mortality.