ArticleThe Journal of clinical endocrinology and metabolism2023
Tissue Glucocorticoid Metabolism in Adrenal Insufficiency: A Prospective Study of Dual-release Hydrocortisone Therapy.
Article in The Journal of clinical endocrinology and metabolism, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 11 citations in OpenAlex.
- Psychological and biological long-term consequences of trauma in the Yazidi population displaced from Shingal after the genocide.European journal of psychotraumatology · 2026Article
- Dyslipidemias associated with endocrine disorders: a position statement of the working group of the nutrition hormones and metabolism club of the italian society of endocrinology (SIE).Journal of endocrinological investigation · 2026Review
- Observational
- Cognitive Assessment in Adults With Adrenal Cortisol Insufficiency: Challenges and Opportunities.Endocrine reviews · 2026Review
- Long-term administration of hydrocortisone: down-regulating the level of cytokine and resulting in injuring testicular tissue of juvenile mice.BMC pharmacology & toxicology · 2025Article
- Mpox Infection and Endocrine Health: Bridging the Knowledge Gap.Medicina (Kaunas, Lithuania) · 2025Review
- Extended-release Hydrocortisone Formulations-Is There a Clinically Meaningful Benefit?The Journal of clinical endocrinology and metabolism · 2025Review
- Effects of glucocorticoid replacement therapy in patients with pituitary disease: A new perspective for personalized replacement therapy.Reviews in endocrine & metabolic disorders · 2024Review
- Fertility and pregnancy in adrenal insufficiency.Endocrine connections · 2024Review
Corrections and comments
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Authors and funding
29 authors at 10 institutions in 3 countries.
Funding
Abstract
backgroundPatients with adrenal insufficiency (AI) require life-long glucocorticoid (GC) replacement therapy. Within tissues, cortisol (F) availability is under the control of the isozymes of 11β-hydroxysteroid dehydrogenase (11β-HSD). We hypothesize that corticosteroid metabolism is altered in patients with AI because of the nonphysiological pattern of current immediate release hydrocortisone (IR-HC) replacement therapy. The use of a once-daily dual-release hydrocortisone (DR-HC) preparation, (Plenadren®), offers a more physiological cortisol profile and may alter corticosteroid metabolism in vivo. STUDY DESIGN AND
methodsProspective crossover study assessing the impact of 12 weeks of DR-HC on systemic GC metabolism (urinary steroid metabolome profiling), cortisol activation in the liver (cortisone acetate challenge test), and subcutaneous adipose tissue (microdialysis, biopsy for gene expression analysis) in 51 patients with AI (primary and secondary) in comparison to IR-HC treatment and age- and BMI-matched controls.
resultsPatients with AI receiving IR-HC had a higher median 24-hour urinary excretion of cortisol compared with healthy controls (72.1 µg/24 hours [IQR 43.6-124.2] vs 51.9 µg/24 hours [35.5-72.3], P = .02), with lower global activity of 11β-HSD2 and higher 5-alpha reductase activity. Following the switch from IR-HC to DR-HC therapy, there was a significant reduction in urinary cortisol and total GC metabolite excretion, which was most significant in the evening. There was an increase in 11β-HSD2 activity. Hepatic 11β-HSD1 activity was not significantly altered after switching to DR-HC, but there was a significant reduction in the expression and activity of 11β-HSD1 in subcutaneous adipose tissue.
conclusionUsing comprehensive in vivo techniques, we have demonstrated abnormalities in corticosteroid metabolism in patients with primary and secondary AI receiving IR-HC. This dysregulation of pre-receptor glucocorticoid metabolism results in enhanced glucocorticoid activation in adipose tissue, which was ameliorated by treatment with DR-HC.
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