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

Stéphanie Espiard | Zendy; Johanna McQueen | Zendy; Mark Sherlock | Zendy; Óskar Ragnarsson | Zendy; Ragnhildur Bergthorsdottir | Zendy; Pia Burman | Zendy; Per Dahlqvist | Zendy; Bertil Ekman | Zendy; Britt Edén Engström | Zendy; Stanko Skrtic | Zendy; Jeanette Wahlberg | Zendy; Paul M. Stewart | Zendy; Gudmundur Johannsson | Zendy

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

Author(s) -

Stéphanie Espiard,

Johanna McQueen,

Mark Sherlock,

Óskar Ragnarsson,

Ragnhildur Bergthorsdottir,

Pia Burman,

Per Dahlqvist,

Bertil Ekman,

Britt Edén Engström,

Stanko Skrtic,

Jeanette Wahlberg,

Paul M. Stewart,

Gudmundur Johannsson

Publication year - 2020

Publication title -

the journal of clinical endocrinology and metabolism

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 2.206

H-Index - 353

eISSN - 1945-7197

pISSN - 0021-972X

DOI - 10.1210/clinem/dgaa862

Subject(s) - medicine , endocrinology , context (archaeology) , hydrocortisone , urinary system , glucocorticoid , cortisone , corticosteroid , crossover study , chemistry , biology , placebo , paleontology , alternative medicine , pathology

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, 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. 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.

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