Cargando…

Residual endogenous corticosteroid production in patients with adrenal insufficiency

OBJECTIVE: This study aimed at comparing precursors of endogenous corticosteroid production in patients with primary adrenal insufficiency and in secondary adrenal insufficiency. DESIGN: Twenty patients with primary adrenal insufficiency and matched controls and 19 patients with secondary adrenal in...

Descripción completa

Detalles Bibliográficos
Autores principales: Vulto, Annet, Bergthorsdottir, Ragnhildur, van Faassen, Martijn, Kema, Ido P., Johannsson, Gudmundur, van Beek, André P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6851705/
https://www.ncbi.nlm.nih.gov/pubmed/31059146
http://dx.doi.org/10.1111/cen.14006
_version_ 1783469672206696448
author Vulto, Annet
Bergthorsdottir, Ragnhildur
van Faassen, Martijn
Kema, Ido P.
Johannsson, Gudmundur
van Beek, André P.
author_facet Vulto, Annet
Bergthorsdottir, Ragnhildur
van Faassen, Martijn
Kema, Ido P.
Johannsson, Gudmundur
van Beek, André P.
author_sort Vulto, Annet
collection PubMed
description OBJECTIVE: This study aimed at comparing precursors of endogenous corticosteroid production in patients with primary adrenal insufficiency and in secondary adrenal insufficiency. DESIGN: Twenty patients with primary adrenal insufficiency and matched controls and 19 patients with secondary adrenal insufficiency participated in this ancillary analysis of two different studies. PATIENTS AND MEASUREMENTS: Patients with primary adrenal insufficiency were on stable hydrocortisone and fludrocortisone therapy. Patients with secondary adrenal insufficiency received two different doses of hydrocortisone in a randomized crossover study. Main outcome measures were concentrations of precursors of cortisol and aldosterone measured by LC‐MS/MS RESULTS: Compared to controls, progressively lower concentrations of the glucocorticoid precursors 11‐deoxycortisol, 11‐deoxycorticosterone and corticosterone concentrations were found in patients with secondary adrenal insufficiency on lower hydrocortisone dose, secondary adrenal insufficiency on higher hydrocortisone dose and primary adrenal insufficiency, respectively. Half of the primary adrenal insufficient patients showed evidence of residual endogenous cortisol or aldosterone synthesis, as determined by quantifiable 11‐deoxycortisol, 11‐deoxycorticosterone and corticosterone conce ntrations. In secondary adrenal insufficient patients with higher endogenous cortisol production, as indicated by 11‐deoxycortisol concentrations above the median, no increased cortisol exposure was observed both by plasma pharmacokinetic parameters and 24‐hour free cortisol excretion in urine. CONCLUSIONS: Adrenal corticosteroid production is likely to continue during treatment in a considerable percentage of patients with both primary and secondary adrenal insufficiency. In patients with secondary adrenal insufficiency, this synthesis appears to be sensitive to the dose of hydrocortisone. However, the residual corticosteroid concentrations were quantitatively low and its clinical significance remains therefore to be determined.
format Online
Article
Text
id pubmed-6851705
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher John Wiley and Sons Inc.
record_format MEDLINE/PubMed
spelling pubmed-68517052019-11-18 Residual endogenous corticosteroid production in patients with adrenal insufficiency Vulto, Annet Bergthorsdottir, Ragnhildur van Faassen, Martijn Kema, Ido P. Johannsson, Gudmundur van Beek, André P. Clin Endocrinol (Oxf) Original Articles OBJECTIVE: This study aimed at comparing precursors of endogenous corticosteroid production in patients with primary adrenal insufficiency and in secondary adrenal insufficiency. DESIGN: Twenty patients with primary adrenal insufficiency and matched controls and 19 patients with secondary adrenal insufficiency participated in this ancillary analysis of two different studies. PATIENTS AND MEASUREMENTS: Patients with primary adrenal insufficiency were on stable hydrocortisone and fludrocortisone therapy. Patients with secondary adrenal insufficiency received two different doses of hydrocortisone in a randomized crossover study. Main outcome measures were concentrations of precursors of cortisol and aldosterone measured by LC‐MS/MS RESULTS: Compared to controls, progressively lower concentrations of the glucocorticoid precursors 11‐deoxycortisol, 11‐deoxycorticosterone and corticosterone concentrations were found in patients with secondary adrenal insufficiency on lower hydrocortisone dose, secondary adrenal insufficiency on higher hydrocortisone dose and primary adrenal insufficiency, respectively. Half of the primary adrenal insufficient patients showed evidence of residual endogenous cortisol or aldosterone synthesis, as determined by quantifiable 11‐deoxycortisol, 11‐deoxycorticosterone and corticosterone conce ntrations. In secondary adrenal insufficient patients with higher endogenous cortisol production, as indicated by 11‐deoxycortisol concentrations above the median, no increased cortisol exposure was observed both by plasma pharmacokinetic parameters and 24‐hour free cortisol excretion in urine. CONCLUSIONS: Adrenal corticosteroid production is likely to continue during treatment in a considerable percentage of patients with both primary and secondary adrenal insufficiency. In patients with secondary adrenal insufficiency, this synthesis appears to be sensitive to the dose of hydrocortisone. However, the residual corticosteroid concentrations were quantitatively low and its clinical significance remains therefore to be determined. John Wiley and Sons Inc. 2019-06-20 2019-09 /pmc/articles/PMC6851705/ /pubmed/31059146 http://dx.doi.org/10.1111/cen.14006 Text en © 2019 The Authors. Clinical Endocrinology Published by John Wiley & Sons Ltd This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Vulto, Annet
Bergthorsdottir, Ragnhildur
van Faassen, Martijn
Kema, Ido P.
Johannsson, Gudmundur
van Beek, André P.
Residual endogenous corticosteroid production in patients with adrenal insufficiency
title Residual endogenous corticosteroid production in patients with adrenal insufficiency
title_full Residual endogenous corticosteroid production in patients with adrenal insufficiency
title_fullStr Residual endogenous corticosteroid production in patients with adrenal insufficiency
title_full_unstemmed Residual endogenous corticosteroid production in patients with adrenal insufficiency
title_short Residual endogenous corticosteroid production in patients with adrenal insufficiency
title_sort residual endogenous corticosteroid production in patients with adrenal insufficiency
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6851705/
https://www.ncbi.nlm.nih.gov/pubmed/31059146
http://dx.doi.org/10.1111/cen.14006
work_keys_str_mv AT vultoannet residualendogenouscorticosteroidproductioninpatientswithadrenalinsufficiency
AT bergthorsdottirragnhildur residualendogenouscorticosteroidproductioninpatientswithadrenalinsufficiency
AT vanfaassenmartijn residualendogenouscorticosteroidproductioninpatientswithadrenalinsufficiency
AT kemaidop residualendogenouscorticosteroidproductioninpatientswithadrenalinsufficiency
AT johannssongudmundur residualendogenouscorticosteroidproductioninpatientswithadrenalinsufficiency
AT vanbeekandrep residualendogenouscorticosteroidproductioninpatientswithadrenalinsufficiency