Diurnal production of cortisol and prediction of treatment response in rheumatoid arthritis: a 6-month, real-life prospective cohort study

Objectives A reduced adrenal reserve-associated cortisol production relative to the enhanced needs of chronic inflammation (disproportion principle) has been observed in rheumatoid arthritis (RA). We examined the possible clinical value of diurnal cortisol measurements in active RA on treatment resp...

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Main Authors: George E Fragoulis, Antonis Fanouriakis, Maria G Tektonidou, Petros P Sfikakis, Gerasimos Evangelatos, Vasiliki-Kalliopi Bournia, Katerina Laskari, Stylianos Panopoulos, GEORGE P CHROUSOS, Maria P Yavropoulou, Maria G Filippa, Nikolaos I Vlachogiannis, Aimilia Mantzou, Aggeliki Papapanagiotou
Format: Article
Language:English
Published: BMJ Publishing Group 2024-02-01
Series:RMD Open
Online Access:https://rmdopen.bmj.com/content/10/1/e003575.full
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author George E Fragoulis
Antonis Fanouriakis
Maria G Tektonidou
Petros P Sfikakis
Gerasimos Evangelatos
Vasiliki-Kalliopi Bournia
Katerina Laskari
Stylianos Panopoulos
GEORGE P CHROUSOS
Maria P Yavropoulou
Maria G Filippa
Nikolaos I Vlachogiannis
Aimilia Mantzou
Aggeliki Papapanagiotou
author_facet George E Fragoulis
Antonis Fanouriakis
Maria G Tektonidou
Petros P Sfikakis
Gerasimos Evangelatos
Vasiliki-Kalliopi Bournia
Katerina Laskari
Stylianos Panopoulos
GEORGE P CHROUSOS
Maria P Yavropoulou
Maria G Filippa
Nikolaos I Vlachogiannis
Aimilia Mantzou
Aggeliki Papapanagiotou
author_sort George E Fragoulis
collection DOAJ
description Objectives A reduced adrenal reserve-associated cortisol production relative to the enhanced needs of chronic inflammation (disproportion principle) has been observed in rheumatoid arthritis (RA). We examined the possible clinical value of diurnal cortisol measurements in active RA on treatment response prediction.Methods Diurnal cortisol production (measured at: 08–12:00/18:00–22:00) was assessed by electrochemiluminescence immunoassay in 28 consecutive patients with moderately/highly active RA, as well as 3 and 6 months after treatment initiation or/escalation. Twenty-eight COVID-19 patients and 28 age-matched healthy individuals (HC) served as controls.Results Saliva diurnal cortisol production in patients with RA was similar to that of HC, despite 12-fold higher serum C reactive protein (CRP) levels, and lower than COVID-19 patients (area under the curve: RA: 87.0±37.6 vs COVID-19: 146.7±14.3, p<0.001), having similarly high CRP. Moreover, a disturbed circadian cortisol rhythm at baseline was evident in 15 of 28 of patients with RA vs 4 of 28 and 20 of 28 of HC and COVID-19 patients, respectively. Treatment-induced minimal disease activity (MDA) at 6 months was achieved by 16 of 28 patients. Despite comparable demographics and clinical characteristics at baseline, non-MDA patients had lower baseline morning cortisol and higher adrenocorticotropic hormone (ACTH) levels compared with patients on MDA (cortisol: 10.9±4.0 vs 18.4±8.2 nmol/L, respectively, p=0.005 and ACTH: 4.8±3.3 vs 2.4±0.4 pmol/L, respectively, p=0.047). Baseline morning cortisol <13.9 nmol/L predicted non-MDA at 6 months (75% sensitivity, 92% specificity, p=0.006). Prospective measurements revealed that individualised diurnal cortisol production remained largely unchanged from baseline to 3 and 6 months.Conclusions An impaired adrenal reserve is present in patients with RA. Further studies to confirm that assessment of diurnal cortisol production may be useful in guiding treatment decisions and/or predicting treatment response in RA are warranted.Trial registration number NCT05671627.
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spelling doaj-art-9f6ca0af305643c684f18bdefca7ec672025-08-20T03:11:52ZengBMJ Publishing GroupRMD Open2056-59332024-02-0110110.1136/rmdopen-2023-003575Diurnal production of cortisol and prediction of treatment response in rheumatoid arthritis: a 6-month, real-life prospective cohort studyGeorge E Fragoulis0Antonis Fanouriakis1Maria G Tektonidou2Petros P Sfikakis3Gerasimos Evangelatos4Vasiliki-Kalliopi Bournia5Katerina Laskari6Stylianos Panopoulos7GEORGE P CHROUSOS8Maria P Yavropoulou9Maria G Filippa10Nikolaos I Vlachogiannis11Aimilia Mantzou12Aggeliki Papapanagiotou13Institute of Infection, Immunity and Inflammation, University of Glasgow School of Medicine, Glasgow, UKth Department of Internal Medicine, National and Kapodistrian University of Athens Medical School, Athens, Greece1 First Department of Propaedeutic Internal Medicine, Laiko Hospital, National and Kapodistrian University of Athens, Athens, GreeceNational and Kapodistrian University of Athens, School of Medicine, Rheumatology Unit, First Department of Propaedeutic Internal Medicine, Athens, GreeceFirst Department of Propaedeutic and Internal Medicine and Joint Academic Rheumatology Program, National and Kapodistrian University of Athens, Athens, GreeceFirst Department of Propaedeutic and Internal Medicine and Joint Academic Rheumatology Program, National and Kapodistrian University of Athens, Athens, Greece21 Rheumatology Unit, 1st Dept. of Propaedeutic Internal Medicine, National & Kapodistrian University of Athens Medical School, Athens, GreeceFirst Department of Propaedeutic and Internal Medicine and Joint Academic Rheumatology Program, National and Kapodistrian University of Athens, Athens, GreeceUniversity Research Institute of Maternal and Child Health and Precision Medicine, National and Kapodistrian University of Athens, Athens, GreeceFirst Department of Propaedeutic and Internal Medicine, Endocrinology Unit, National and Kapodistrian University of Athens, Athens, GreeceFirst Department of Propaedeutic and Internal Medicine, Endocrinology Unit, National and Kapodistrian University of Athens, Athens, GreeceFirst Department of Propaedeutic and Internal Medicine and Joint Academic Rheumatology Program, National and Kapodistrian University of Athens, Athens, GreeceUniversity Research Institute of Maternal and Child Health and Precision Medicine, National and Kapodistrian University of Athens, Athens, GreeceDepartment of Biological Chemistry, National and Kapodistrian University of Athens, Athens, GreeceObjectives A reduced adrenal reserve-associated cortisol production relative to the enhanced needs of chronic inflammation (disproportion principle) has been observed in rheumatoid arthritis (RA). We examined the possible clinical value of diurnal cortisol measurements in active RA on treatment response prediction.Methods Diurnal cortisol production (measured at: 08–12:00/18:00–22:00) was assessed by electrochemiluminescence immunoassay in 28 consecutive patients with moderately/highly active RA, as well as 3 and 6 months after treatment initiation or/escalation. Twenty-eight COVID-19 patients and 28 age-matched healthy individuals (HC) served as controls.Results Saliva diurnal cortisol production in patients with RA was similar to that of HC, despite 12-fold higher serum C reactive protein (CRP) levels, and lower than COVID-19 patients (area under the curve: RA: 87.0±37.6 vs COVID-19: 146.7±14.3, p<0.001), having similarly high CRP. Moreover, a disturbed circadian cortisol rhythm at baseline was evident in 15 of 28 of patients with RA vs 4 of 28 and 20 of 28 of HC and COVID-19 patients, respectively. Treatment-induced minimal disease activity (MDA) at 6 months was achieved by 16 of 28 patients. Despite comparable demographics and clinical characteristics at baseline, non-MDA patients had lower baseline morning cortisol and higher adrenocorticotropic hormone (ACTH) levels compared with patients on MDA (cortisol: 10.9±4.0 vs 18.4±8.2 nmol/L, respectively, p=0.005 and ACTH: 4.8±3.3 vs 2.4±0.4 pmol/L, respectively, p=0.047). Baseline morning cortisol <13.9 nmol/L predicted non-MDA at 6 months (75% sensitivity, 92% specificity, p=0.006). Prospective measurements revealed that individualised diurnal cortisol production remained largely unchanged from baseline to 3 and 6 months.Conclusions An impaired adrenal reserve is present in patients with RA. Further studies to confirm that assessment of diurnal cortisol production may be useful in guiding treatment decisions and/or predicting treatment response in RA are warranted.Trial registration number NCT05671627.https://rmdopen.bmj.com/content/10/1/e003575.full
spellingShingle George E Fragoulis
Antonis Fanouriakis
Maria G Tektonidou
Petros P Sfikakis
Gerasimos Evangelatos
Vasiliki-Kalliopi Bournia
Katerina Laskari
Stylianos Panopoulos
GEORGE P CHROUSOS
Maria P Yavropoulou
Maria G Filippa
Nikolaos I Vlachogiannis
Aimilia Mantzou
Aggeliki Papapanagiotou
Diurnal production of cortisol and prediction of treatment response in rheumatoid arthritis: a 6-month, real-life prospective cohort study
RMD Open
title Diurnal production of cortisol and prediction of treatment response in rheumatoid arthritis: a 6-month, real-life prospective cohort study
title_full Diurnal production of cortisol and prediction of treatment response in rheumatoid arthritis: a 6-month, real-life prospective cohort study
title_fullStr Diurnal production of cortisol and prediction of treatment response in rheumatoid arthritis: a 6-month, real-life prospective cohort study
title_full_unstemmed Diurnal production of cortisol and prediction of treatment response in rheumatoid arthritis: a 6-month, real-life prospective cohort study
title_short Diurnal production of cortisol and prediction of treatment response in rheumatoid arthritis: a 6-month, real-life prospective cohort study
title_sort diurnal production of cortisol and prediction of treatment response in rheumatoid arthritis a 6 month real life prospective cohort study
url https://rmdopen.bmj.com/content/10/1/e003575.full
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