Hydrocortisone Versus Methylprednisolone for the Treatment of Glucocorticoid-Induced Adrenal Insufficiency
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: Patients will receive 3 mg of methylprednisolone once daily. The dose is administered in the morning (1 ½ tablets of 2 mg Medrol after breakfast)., Patients will receive 15 mg of hydrocortisone daily. The dose is split into 10 mg in the morning after breakfast and 5 mg after 6-7 hours..
- Who it may be relevant to
- Registry conditions: Adrenal Insufficiency. Basic parameters: from 18 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- Slovenia
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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Overview
This study aims to compare the use of methylprednisolone and hydrocortisone as replacement therapies in patients with glucocorticoid-induced adrenal insufficiency. The primary goal is to evaluate and compare the recovery of the hypothalamic-pituitary-adrenal (HPA) axis.
Detailed description
Glucocorticoids in supraphysiological doses are the most frequent cause of adrenal insufficiency due to the suppression of the hypothalamic-pituitary-adrenal (HPA) axis.
In cases of confirmed adrenal insufficiency, current guidelines recommend replacement therapy with physiological doses of short- and intermediate-acting glucocorticoids to prevent adrenal crises without inhibiting HPA axis recovery.
While hydrocortisone is the most commonly used short-acting glucocorticoid, methylprednisolone is widely prescribed in Slovenia.
Because methylprednisolone lacks mineralocorticoid effects, it appears to be a particularly suitable choice for patients with glucocorticoid-induced adrenal insufficiency, where mineralocorticoid secretion is not impaired.
This randomized, prospective, open-label interventional study will primarily evaluate non-inferiority regarding HPA axis recovery after 12 months, with a long-term assessment at 24 months.
Patients will undergo testing at baseline, 3, 6,12, 18, 24 months (or until HPA axis recovery), including laboratory tests, short ACTH tests, body composition measurements, and quality of life questionnaires.
Interventions
- Drug Patients will receive 3 mg of methylprednisolone once daily. The dose is administered in the morning (1 ½ tablets of 2 mg Medrol after breakfast).
Patients will receive 3 mg of methylprednisolone once daily. The dose is administered in the morning (1 ½ tablets of 2 mg methylprednisolone after breakfast). - Drug Patients will receive 15 mg of hydrocortisone daily. The dose is split into 10 mg in the morning after breakfast and 5 mg after 6-7 hours.
Patients will receive 15 mg of hydrocortisone daily. The dose is split into 10 mg in the morning after breakfast and 5 mg after 6-7 hours.
Primary outcome measures
- Proportion of patients with recovery of the HPA axis. [Time frame: 12 months]
Secondary outcome measures (12)
- Secondary Analysis: Superiority of Methylprednisolone [Time frame: 12 months]
- Non-inferiority of Methylprednisolone at 24 Months [Time frame: 24 months]
- Number of adrenal crises. [Time frame: 24 months]
- Time required for HPA axis recovery based on the duration of previous glucocorticoid treatment. [Time frame: up to 24 months]
- Predictive Value of Morning Serum Cortisol Concentration [Time frame: Baseline, 3, 6, 12, 18, 24 months.]
- Predictive Value of Serum Dehydroepiandrosterone Sulfate (DHEA-S) [Time frame: Baseline, 3 months, 6 months, 12 months, 18 months and 24 months]
- Predictive Value of Morning Salivary Cortisone [Time frame: Baseline, 3 months, 6 months, 12 months, 18 months and 24 months]
- Change from Baseline in Glycated Hemoglobin (HbA1c) [Time frame: Baseline, 3, 6, 12, 18, 24 months]
- Change from Baseline in Fasting Glucose [Time frame: Baseline, 3, 6, 12, 18 and 24 months]
- Change from Baseline in Lipid Profile [Time frame: Baseline, 3 months, 6 months, 12 months, 18 months, 24 months]
- Change from Baseline in Body Fat Percentage and Visceral Fat Mass [Time frame: Baseline, 12 months and 24 months]
- Change from Baseline in Bone Mineral Density (BMD) [Time frame: baseline, 12 and 24 months]
Eligibility criteria
Inclusion criteria
- Age over 18 years.
- Suspected adrenal insufficiency due to receiving supraphysiological doses of methylprednisolone for more than 4 weeks.
- Receiving methylprednisolone 4 mg for at least the last 4 weeks.
- Morning cortisol lower than 300 nmol/L.
- Inadequate result of a short ACTH test performed on a physiological dose of methylprednisolone (cortisol rise after 30 min under 470 nmol/L AND after 60 min under 500 nmol/L).
- No further indication for treating the underlying disease, and retreatment with glucocorticoids is not expected in the next 2 years.
- Consent to participate in the research.
Exclusion criteria
- Known organic disease of the pituitary-adrenal axis.
- Body mass over 130 kg.
- Advanced comorbidities.
- Advanced heart failure (NYHA IV).
- Chronic kidney disease IV, eGFR under 30 ml/min.
- Liver cirrhosis.
- Active malignant disease.
- Immune deficiencies.
- Planned major surgery during the study duration.
- Receiving drugs affecting cortisol metabolism or interfering with cortisol measurements (e.g., systemic estrogens, strong inducers or inhibitors of CYP3A4).
- Conditions affecting cortisol metabolism (pregnancy, liver disease, nephrotic syndrome).
- Alcohol dependence syndrome (consuming more than 21 units of alcohol per week).
- Shift (night) work.
- Presence of comorbidities with an expected life expectancy of less than 3 years.
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Allocation
- Randomized
- Model
- Parallel assignment
- Masking
- Open label
- Primary purpose
- Treatment
Study locations
Slovenia · 1 center
- UMC Ljubljana — Ljubljana
Identifiers
NCT: NCT07703098 · 0120-87/2026-2711-4