Trial reportThe Journal of clinical endocrinology and metabolism2021
Improved Urinary Cortisol Metabolome in Addison Disease: A Prospective Trial of Dual-Release Hydrocortisone.
Trial report in The Journal of clinical endocrinology and metabolism, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
7 citing papers in PubMed, 12 citations in OpenAlex.
- Different metabolic pathways associated with total cortisol exposure and the cortisol time profile: a randomized crossover trial.Scientific reports · 2026Trial
- Extended-release Hydrocortisone Formulations-Is There a Clinically Meaningful Benefit?The Journal of clinical endocrinology and metabolism · 2025Review
- Current Challenges and Future Directions in the Assessment of Glucocorticoid Status.Endocrine reviews · 2024Review
- Health-Related Quality of Life in Patients with Primary Adrenal Insufficiency.Journal of clinical medicine · 2023Article
- Tissue Glucocorticoid Metabolism in Adrenal Insufficiency: A Prospective Study of Dual-release Hydrocortisone Therapy.The Journal of clinical endocrinology and metabolism · 2023Article
- Pseudohypoadrenalism, a subclinical cortisol metabolism disorder in hyperuricemia.Frontiers in endocrinology · 2023Article
- Trabecular bone score and sclerostin concentrations in patients with primary adrenal insufficiency.Frontiers in endocrinology · 2022Article
Corrections and comments
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Authors and funding
13 authors at 7 institutions in 3 countries.
Funding
Abstract
contextOral once-daily dual-release hydrocortisone (DR-HC) replacement therapy has demonstrated an improved metabolic profile compared to conventional 3-times-daily (TID-HC) therapy among patients with primary adrenal insufficiency. This effect might be related to a more physiological cortisol profile, but also to a modified pattern of cortisol metabolism.
objectiveThis work aimed to study cortisol metabolism during DR-HC and TID-HC.
designA randomized, 12-week, crossover study was conducted. INTERVENTION AND
participantsDC-HC and same daily dose of TID-HC were administered to patients with primary adrenal insufficiency (n = 50) vs healthy individuals (n = 124) as controls.
main outcome measuresUrinary corticosteroid metabolites were measured by gas chromatography/mass spectrometry at 24-hour urinary collections.
resultsTotal cortisol metabolites decreased during DR-HC compared to TID-HC (P < .001) and reached control values (P = .089). During DR-HC, 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) activity measured by tetrahydrocortisol + 5α-tetrahydrocortisol/tetrahydrocortisone ratio was reduced compared to TID-HC (P < .05), but remained increased vs controls (P < .001). 11β-HSD2 activity measured by urinary free cortisone/free cortisol ratio was decreased with TID-HC vs controls (P < .01) but normalized with DR-HC (P = .358). 5α- and 5β-reduced metabolites were decreased with DR-HC compared to TID-HC. Tetrahydrocortisol/5α-tetrahydrocortisol ratio was increased during both treatments, suggesting increased 5β-reductase activity.
conclusionsThe urinary cortisol metabolome shows striking abnormalities in patients receiving conventional TID-HC replacement therapy, with increased 11β-HSD1 activity that may account for the unfavorable metabolic phenotype in primary adrenal insufficiency. Its change toward normalization with DR-HC may mediate beneficial metabolic effects. The urinary cortisol metabolome may serve as a tool to assess optimal cortisol replacement therapy.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.