Improved Urinary Cortisol Metabolome in Addison's disease: a Prospective Trial of Dual-Release Hydrocortisone.

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Improved Urinary Cortisol Metabolome in Addison's disease: a Prospective Trial of Dual-Release Hydrocortisone.

Espiard, Stéphanie (author): University of Gothenburg,Gothenburg University,Göteborgs universitet,Institutionen för medicin,Institute of Medicine,Department of Endocrinology, Sahlgrenska University Hospital and Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.,Univ Gothenburg, Sahlgrenska Univ Hosp, Sahlgrenska Acad, Dept Endocrinol, S-41345 Gothenburg, Sweden.;Univ Gothenburg, Sahlgrenska Univ Hosp, Inst Med, S-41345 Gothenburg, Sweden.

Mcqueen, Johanna (author): University of Gothenburg,Gothenburg University,Göteborgs universitet,Institutionen för medicin,Institute of Medicine,Department of Endocrinology, Sahlgrenska University Hospital and Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.,Univ Gothenburg, Sahlgrenska Univ Hosp, Sahlgrenska Acad, Dept Endocrinol, S-41345 Gothenburg, Sweden.;Univ Gothenburg, Sahlgrenska Univ Hosp, Inst Med, S-41345 Gothenburg, Sweden.

Sherlock, Mark (author): Department of Endocrinology, Beaumont Hospital and Royal College of Surgeons in Ireland, Co. Dublin 9, Ireland.,Beaumont Hosp, Dept Endocrinol, Dublin 9, Co Dublin, Ireland.;Royal Coll Surgeons Ireland, Dublin 9, Co Dublin, Ireland.

Ragnarsson, Oskar, 1971 (author): University of Gothenburg,Gothenburg University,Göteborgs universitet,Institutionen för medicin,Institute of Medicine,Department of Endocrinology, Sahlgrenska University Hospital and Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.,Univ Gothenburg, Sahlgrenska Univ Hosp, Sahlgrenska Acad, Dept Endocrinol, S-41345 Gothenburg, Sweden.;Univ Gothenburg, Sahlgrenska Univ Hosp, Inst Med, S-41345 Gothenburg, Sweden.

Bergthorsdottir, Ragnhildur, 1971 (author): University of Gothenburg,Gothenburg University,Göteborgs universitet,Institutionen för medicin,Institute of Medicine,Department of Endocrinology, Sahlgrenska University Hospital and Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.,Univ Gothenburg, Sahlgrenska Univ Hosp, Sahlgrenska Acad, Dept Endocrinol, S-41345 Gothenburg, Sweden.;Univ Gothenburg, Sahlgrenska Univ Hosp, Inst Med, S-41345 Gothenburg, Sweden.

Burman, Pia (author): Lund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups,Skåne University Hospital,Skane Univ Hosp Malmö, Dept Endocrinol, S-21428 Malmö, Sweden.;Lund Univ, S-22100 Lund, Sweden.

Dahlqvist, Per (author): Umeå University,Umeå universitet,Avdelningen för medicin,Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden.,Umeå Univ, Dept Publ Hlth & Clin Med, S-90187 Umeå, Sweden.

Ekman, Bertil, 1958- (author): Linköping University,Linköpings universitet,Avdelningen för diagnostik och specialistmedicin,Medicinska fakulteten,Region Östergötland, Endokrinmedicinska kliniken

Edén Engström, Britt (author): Uppsala universitet,Endokrinologi och mineralmetabolism,Uppsala Univ Hosp, Dept Med Sci Endocrinol & Metab, S-75237 Uppsala, Sweden.

Skrtic, Stanko, 1970 (author): University of Gothenburg,Gothenburg University,Göteborgs universitet,Institutionen för medicin,Institute of Medicine,Department of Endocrinology, Sahlgrenska University Hospital and Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; AstraZeneca R&D, Mölndal, Sweden,Univ Gothenburg, Sahlgrenska Univ Hosp, Sahlgrenska Acad, Dept Endocrinol, S-41345 Gothenburg, Sweden.;Univ Gothenburg, Sahlgrenska Univ Hosp, Inst Med, S-41345 Gothenburg, Sweden.;AstraZeneca R&D, S-43150 Mölndal, Sweden.

Wahlberg, Jeanette, 1969- (author): Linköping University,Linköpings universitet,Avdelningen för diagnostik och specialistmedicin,Medicinska fakulteten,Region Östergötland, Endokrinmedicinska kliniken,Linköping Univ, Dept Endocrinol, Dept Med & Hlth Sci, Dept Clin & Expt Med, S-58183 Linköping, Sweden.

Stewart, Paul M (author): Faculty of Medicine and Health, University of Leeds, Leeds, UK.,Univ Leeds, Fac Med & Hlth, Leeds LS2 9JT, W Yorkshire, England.

Johannsson, Gudmundur, 1960 (author): University of Gothenburg,Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för invärtesmedicin och klinisk nutrition,Institute of Medicine, Department of Internal Medicine and Clinical Nutrition,Department of Endocrinology, Sahlgrenska University Hospital and Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.,Univ Gothenburg, Sahlgrenska Univ Hosp, Sahlgrenska Acad, Dept Endocrinol, S-41345 Gothenburg, Sweden.;Univ Gothenburg, Sahlgrenska Univ Hosp, Inst Med, S-41345 Gothenburg, Sweden.

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2020-11-24
2021
English.
In: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 106:3, s. 814-825

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Journal article (peer-reviewed)

Abstract Subject headings

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.To study cortisol metabolism during DR-HC and TID-HC.Randomized, 12-week, crossover study.DC-HC and same daily dose of TID-HC in patients with primary adrenal insufficiency (n=50) versus healthy subjects (n=124) as control.Urinary corticosteroid metabolites measured by gas chromatography/mass spectrometry on 24-hour urinary collections.Total cortisol metabolites decreased during DR-HC compared to TID-HC (P < 0.001) and reached control values (P = 0.089). 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 < 0.05), but remained increased versus controls (P < 0.001). 11β-HSD2 activity measured by urinary free cortisone/free cortisol ratio was decreased with TID-HC versus controls (P < 0.01) but normalized with DR-HC (P = 0.358). 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.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 towards normalization with DR-HC may mediate beneficial metabolic effects. The urinary cortisol metabolome may serve as a tool to assess optimal cortisol replacement therapy.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Klinisk laboratoriemedicin (hsv//swe)
MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Clinical Laboratory Medicine (hsv//eng)

Keyword

primary adrenal insufficiency
Addison disease
hydrocortisone
dual-release hydrocortisone
cortisol metabolism
11β-hydroxysteroid dehydrogenase
11β-hydroxysteroid dehydrogenase

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