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Improved Urinary Cortisol Metabolome in Addison Disease: A Prospective Trial of Dual-Release Hydrocortisone.

Authors :
Espiard S
McQueen J
Sherlock M
Ragnarsson O
Bergthorsdottir R
Burman P
Dahlqvist P
Ekman B
Engström BE
Skrtic S
Wahlberg J
Stewart PM
Johannsson G
Source :
The Journal of clinical endocrinology and metabolism [J Clin Endocrinol Metab] 2021 Mar 08; Vol. 106 (3), pp. 814-825.
Publication Year :
2021

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.<br />Objective: This work aimed to study cortisol metabolism during DR-HC and TID-HC.<br />Design: A randomized, 12-week, crossover study was conducted.<br />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.<br />Main Outcome Measures: Urinary corticosteroid metabolites were measured by gas chromatography/mass spectrometry at 24-hour urinary collections.<br />Results: Total 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.<br />Conclusions: The 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.<br /> (© The Author(s) 2020. Published by Oxford University Press on behalf of the Endocrine Society.)

Details

Language :
English
ISSN :
1945-7197
Volume :
106
Issue :
3
Database :
MEDLINE
Journal :
The Journal of clinical endocrinology and metabolism
Publication Type :
Academic Journal
Accession number :
33236103
Full Text :
https://doi.org/10.1210/clinem/dgaa862