CoChat
Sign Up
Cited by 211Adrenal Hormones and DisordersStress Responses and CortisolHormonal and reproductive studies

Effect of once-daily, modified-release hydrocortisone versus standard glucocorticoid therapy on metabolism and innate immunity in patients with adrenal insufficiency (DREAM): a single-blind, randomised controlled trial

Isidori, Andrea M, Venneri, Mary Anna, Graziadio, Chiara, Simeoli, Chiara, Fiore, Daniela, Hasenmajer, Valeria, Sbardella, Emilia, Gianfrilli, Daniele +8 more·2018·The Lancet Diabetes & Endocrinology
DOI 10.1016/s2213-8587(17)30398-4
Open this paper in CoChat — free account

Abstract

Background Conventional treatment of patients with adrenal insufficiency involves administration of glucocorticoids multiple times a day and has been associated with weight gain and metabolic impairment. The optimal glucocorticoid replacement therapy for these patients is highly debated because of the scarcity of evidence from randomised trials. We aimed to establish whether the timing and pharmacokinetics of glucocorticoid replacement therapy affect the metabolism and immune system of patients with adrenal insufficiency.Methods We did a single-blind randomised controlled trial at two reference university hospitals in Italy. Eligible patients (aged 18-80 years) with adrenal insufficiency were on conventional glucocorticoid therapy and had been stable for at least 3 months before enrolment. Patients were randomly assigned (1:1) with a computer-generated random sequence stratified by type of adrenal insufficiency and BMI to continue conventional glucocorticoid therapy (standard treatment group) or to switch to an equivalent dose of once-daily, modified-release oral hydrocortisone (switch treatment group). Outcome assessors were masked to treatment allocation. The primary outcome was bodyweight change from baseline to 24 weeks. Secondary outcomes included immune cell profiles, susceptibility to infections, and quality of life. Efficacy analyses included all patients who received at least one dose of the study drug. This trial is registered with ClinicalTrials.gov, NCT02277587.Findings Between March 1, 2014, and June 30, 2016, 89 patients with adrenal insufficiency were randomly assigned to continue standard glucocorticoid therapy (n=43) or to switch to once-daily, modified-release hydrocortisone (n=46). At 24 weeks, bodyweight reduction was superior in patients in the once-daily hydrocortisone group compared with those in the standard treatment group (-2·1 kg [95% CI -4·0 to -0·3] vs 1·9 kg [-0·1 to 3·9]; treatment difference -4·0 kg, 95% CI -6·9 to -1·1; p=0·008). Additionally, patients in the once-daily hydrocortisone group had more normal immune cell profiles, reduced susceptibility to infections, and improved quality of life compared with the standard glucocorticoid therapy group. We observed no difference in frequency or severity of adverse events between the two intervention groups, although a lower cumulative number of recurrent upper respiratory tract infections was observed with once-daily hydrocortisone than with standard treatment (17 vs 38; p=0·016). Most adverse events were mild; three serious adverse events occurred in each group, of which one adverse advent (arthritis) in the switch treatment group could be considered drug related.Interpretation Patients with adrenal insufficiency on conventional glucocorticoid replacement therapy multiple times a day exhibit a pro-inflammatory state and weakened immune defence. Restoration of a more physiological circadian glucocorticoid rhythm by switching to a once-daily, modified-release regimen reduces bodyweight, normalises the immune cell profile, reduces recurrent infections, and improves the quality of life of patients with adrenal insufficiency.Funding Italian Ministry of University and Research.

Integrity signals

Registry

Crossref · 10.1016/s2213-8587(17)30398-4

Cites

41 of 41 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Related

Authors
Isidori, A. M., Venneri, M. A., Graziadio, C., Simeoli, C., Fiore, D., Hasenmajer, V., Sbardella, E., Gianfrilli, D., Pozza, C., Pasqualetti, P., Morrone, S., Santoni, A., Naro, F., Colao, A., Pivonello, R., & Lenzi, A.
Affiliations
  • Sapienza University of Rome (IT)
  • University of Naples Federico II (IT)
  • Fatebenefratelli Hospital (IT)
  • Istituto Pasteur (IT)
Corresponding author
Isidori, Andrea M
ORCID
Venue
The Lancet Diabetes & Endocrinology
Publisher
Elsevier BV
Published
2018-03
Volume
6
Issue
3
Pages
173-185
ISSN
2213-8587 (ISSN-L)
DOI
10.1016/s2213-8587(17)30398-4
OpenAlex
W2771495007
Semantic Scholar
50739ec7b75075121a5b6d045ac1e69b67ab4f7b
Cited by
211
References
41
Citations by year
2026: 18 · 2025: 17 · 2024: 21 · 2023: 21 · 2022: 20 · 2021: 30 · 2020: 37 · 2019: 23 · 2018: 23 · 2017: 1
FWCI
18.14
Type
journal article
Language
en
Open access
closed
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • The Lancet Diabetes & Endocrinology (publishedVersion)
  • PubMed (publishedVersion)
  • IRIS Research product catalog (Sapienza University of Rome) (submittedVersion)
Funders
Ministero dell’Istruzione, dell’Università e della Ricerca (2015ZTT5KB, RBAP109BLT)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
  • Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
Keywords
adrenal insufficiency, cortisol, glucocorticoid replacement therapy, once-daily dosing, modified-release hydrocortisone, body weight, weight gain, innate immunity, immune cell profiles, infection susceptibility, quality of life, metabolic dysfunction, glucocorticoid pharmacokinetics, DREAM trial, Addison's disease, secondary adrenal insufficiency
MeSH terms
Adolescent, Adrenal Insufficiency, Adult, Aged, Anti-Inflammatory Agents, Body Weight, Circadian Rhythm, Drug Administration Schedule, Female, Glucocorticoids, Humans, Hydrocortisone, Immunity, Innate, Male, Middle Aged, Prognosis, Quality of Life, Biomarkers, Single-Blind Method, Young Adult

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review