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Improved Urinary Cortisol Metabolome in Addison Disease: A Prospective Trial of Dual-Release Hydrocortisone.
Espiard, Stéphanie; McQueen, Johanna; Sherlock, Mark; Ragnarsson, Oskar; Bergthorsdottir, Ragnhildur; Burman, Pia; Dahlqvist, Per; Ekman, Bertil; Engström, Britt Edén; Skrtic, Stanko; Wahlberg, Jeanette; Stewart, Paul M; Johannsson, Gudmundur.
  • Espiard S; Department of Endocrinology, Sahlgrenska University Hospital and Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
  • McQueen J; Department of Endocrinology, Sahlgrenska University Hospital and Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
  • Sherlock M; Department of Endocrinology, Beaumont Hospital and Royal College of Surgeons in Ireland, Co. Dublin 9, Ireland.
  • Ragnarsson O; Department of Endocrinology, Sahlgrenska University Hospital and Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
  • Bergthorsdottir R; Department of Endocrinology, Sahlgrenska University Hospital and Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
  • Burman P; Department of Endocrinology, Skåne University Hospital Malmö, Malmö and University of Lund, Lund, Sweden.
  • Dahlqvist P; Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden.
  • Ekman B; Department of Endocrinology, Department of Medical and Health Sciences, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
  • Engström BE; Department of Medical Sciences, Endocrinology and Metabolism, Uppsala University Hospital, Uppsala, Sweden.
  • Skrtic S; Department of Endocrinology, Sahlgrenska University Hospital and Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
  • Wahlberg J; AstraZeneca R&D, Mölndal, Sweden.
  • Stewart PM; Department of Endocrinology, Department of Medical and Health Sciences, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
  • Johannsson G; Faculty of Medicine and Health, University of Leeds, Leeds, UK.
J Clin Endocrinol Metab ; 106(3): 814-825, 2021 03 08.
Article en En | MEDLINE | ID: mdl-33236103
ABSTRACT
CONTEXT Oral 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.

OBJECTIVE:

This work aimed to study cortisol metabolism during DR-HC and TID-HC.

DESIGN:

A randomized, 12-week, crossover study was conducted. INTERVENTION AND

PARTICIPANTS:

DC-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

MEASURES:

Urinary corticosteroid metabolites were measured by gas chromatography/mass spectrometry at 24-hour urinary collections.

RESULTS:

Total cortisol metabolites decreased during DR-HC compared to TID-HC (P < .001) and reached control values (P = .089). During DR-HC, 11ß-hydroxysteroid dehydrogenase type 1 (11ß-HSD1) activity measured by tetrahydrocortisol + 5α-tetrahydrocortisol/tetrahydrocortisone ratio was reduced compared to TID-HC (P < .05), but remained increased vs controls (P < .001). 11ß-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 5ß-reduced metabolites were decreased with DR-HC compared to TID-HC. Tetrahydrocortisol/5α-tetrahydrocortisol ratio was increased during both treatments, suggesting increased 5ß-reductase activity.

CONCLUSIONS:

The urinary cortisol metabolome shows striking abnormalities in patients receiving conventional TID-HC replacement therapy, with increased 11ß-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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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Esteroides / Hidrocortisona / Enfermedad de Addison Tipo de estudio: Clinical_trials Límite: Adult / Aged / Female / Humans / Male / Middle aged País como asunto: Europa Idioma: En Año: 2021 Tipo del documento: Article
Texto completo
Imprimir
XML
PubMed Links
Search on Google

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Esteroides / Hidrocortisona / Enfermedad de Addison Tipo de estudio: Clinical_trials Límite: Adult / Aged / Female / Humans / Male / Middle aged País como asunto: Europa Idioma: En Año: 2021 Tipo del documento: Article