Diurnal production of cortisol and prediction of treatment response in rheumatoid arthritis: a 6-month, real-life prospective cohort study
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
Affiliations
George E Fragoulis
First Department of Propaedeutic and Internal Medicine and Joint Academic Rheumatology Program, National and Kapodistrian University of Athens, Athens, Greece
Antonis Fanouriakis
”Attikon” University Hospital, Rheumatology and Clinical Immunology, Athens, Greece
Maria G Tektonidou
First Department of Propaedeutic and Internal Medicine and Joint Academic Rheumatology Program, National and Kapodistrian University of Athens, Athens, Greece
Petros P Sfikakis
First Department of Propaedeutic and Internal Medicine and Joint Academic Rheumatology Program, National and Kapodistrian University of Athens, Athens, Greece
Gerasimos Evangelatos
NIMTS Hospital, Rheumatology Unit, Athens, Greece
Vasiliki-Kalliopi Bournia
1National and Kapodistrian University of Athens, Medical School, First Department of Propaedeutic and Internal Medicine, Athens, Greece
Katerina Laskari
First Department of Propaedeutic and Internal Medicine and Joint Academic Rheumatology Program, National and Kapodistrian University of Athens, Athens, Greece
Stylianos Panopoulos
1Joint Rheumatology Program, National and Kapodistrian University of athens Medical School, athens, Greece
GEORGE P CHROUSOS
University Research Institute of Maternal and Child Health and Precision Medicine, National and Kapodistrian University of Athens, Athens, Greece
Maria P Yavropoulou
First Department of Propaedeutic and Internal Medicine, Endocrinology Unit, National and Kapodistrian University of Athens, Athens, Greece
Maria G Filippa
First Department of Propaedeutic and Internal Medicine, Endocrinology Unit, National and Kapodistrian University of Athens, Athens, Greece
Nikolaos I Vlachogiannis
First Department of Propaedeutic and Internal Medicine and Joint Academic Rheumatology Program, National and Kapodistrian University of Athens, Athens, Greece
Aimilia Mantzou
University Research Institute of Maternal and Child Health and Precision Medicine, National and Kapodistrian University of Athens, Athens, Greece
Aggeliki Papapanagiotou
Department of Biological Chemistry, National and Kapodistrian University of Athens, Athens, Greece
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.
