Prednisolone Once Daily vs Hydrocortisone Thrice Daily in Hypoadrenalism: A Randomized Clinical Trial
Authors' conclusion
In this randomized clinical trial, once-daily low-dose prednisolone was associated with slower bone turnover and improvements in cardiometabolic health markers compared with multiple-dose hydrocortisone without compromising well-being. Studies assessing longer-term mortality and morbidity outcomes are needed.
Study context
- Population
- Adults with adrenal insufficiency; median (IQR) age 55.0 (46.5–62.8) years; 52.2% male46 analysed
- Participants
- 47 adults
- Comparison
- Once-daily low-dose prednisolone vs thrice-daily hydrocortisone
- Primary endpoint
- Bone turnover: change in carboxylated and undercarboxylated osteocalcin in each treatment period
- Follow-up
- Days 1 to 120
Methodological detailsdouble-blind, crossover, September 3, 2019, to December 14, 2023, 24 received prednisolone first and 22 hydrocortisone first
- Double-blind
- Crossover
- September 3, 2019, to December 14, 2023
- 24 received prednisolone first and 22 hydrocortisone first
Primary result
As reported in the abstract
Bone turnover markers (osteocalcin)
Prednisolone vs HydrocortisoneMean treatment difference, ng/mL (95% CI)P value
Carboxylated osteocalcin; lower with prednisolone
−1.22(−2.35 to −0.10)
P = 0.04Undercarboxylated osteocalcin; lower with prednisolone
−1.38(−2.32 to −0.44)
P = 0.005Secondary outcomes
| Outcome | Mean treatment difference (nmol/mmol) (95% CI) | P value | |
|---|---|---|---|
| Other bone markersPrednisolonevs HydrocortisoneUrinary N-terminal telopeptide | −9.34 (−15.4 to −3.29) | P = 0.002 | |
| −20−10010Difference, nmol/mmol (linear scale) |
| Outcome | Mean treatment difference (ng/mL) (95% CI) | P value | |
|---|---|---|---|
| Other bone markersPrednisolonevs HydrocortisoneP1NP | −13.8 (−22.2 to −5.49) | P < 0.001 | |
| −30−20−10010Difference, ng/mL (linear scale) |
| Outcome | Mean treatment group difference (kg) (95% CI) | P value | |
|---|---|---|---|
| Weight and cardiometabolic markersPrednisolonevs HydrocortisoneWeight reduction from baseline | −1.87 (−3.02 to −0.72) | P = 0.002 | |
| −4−202Difference, kg (linear scale) |
| Outcome | Treatment difference (95% CI) | P value | |
|---|---|---|---|
| Weight and cardiometabolic markersPrednisolonevs HydrocortisoneBMI; greater reduction with prednisolone | −0.522 (−1.01 to −0.04) | P = 0.04 | |
| −1.5−1−0.500.5Difference (linear scale) |
| Outcome | Treatment difference (cm) (95% CI) | P value | |
|---|---|---|---|
| Weight and cardiometabolic markersPrednisolonevs HydrocortisoneWaist circumference; greater reduction with prednisolone | −2.26 (−3.97 to −0.56) | P = 0.01 | |
| −4−202Difference, cm (linear scale) |
| Outcome | Treatment difference (%) | P value |
|---|---|---|
| Weight and cardiometabolic markersPrednisolone vs Hydrocortisone · HbA1c; −1.23 mmol/mol (95% CI −1.95 to −0.51 mmol/mol) | −0.12 | P = 0.001 |
Subjective health outcomes
- No differences, including all SF-36 domains and Addison's Disease-Specific Quality of Life Questionnaire
Safety
- No differences in safety measures
Original publication
Prednisolone Once Daily vs Hydrocortisone Thrice Daily in Hypoadrenalism: A Randomized Clinical Trial. JAMA Netw Open. Published 2 March 2026. doi:10.
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