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

Maria P Yavropoulou; Maria G Filippa; Nikolaos I Vlachogiannis; George E Fragoulis; Katerina Laskari; Aimilia Mantzou; Stylianos Panopoulos; Antonis Fanouriakis; Vasiliki-Kalliopi Bournia; Gerasimos Evangelatos; Aggeliki Papapanagiotou; Maria G Tektonidou; George P Chrousos; Petros P Sfikakis

doi:10.1136/rmdopen-2023-003575

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

RMD Open. 2024 Jan 17;10(1):e003575. doi: 10.1136/rmdopen-2023-003575.

Authors

Affiliations

¹ First Department of Propaedeutic and Internal Medicine, Endocrinology Unit, National and Kapodistrian University of Athens, Athens, Greece.
² First Department of Propaedeutic and Internal Medicine and Joint Academic Rheumatology Program, National and Kapodistrian University of Athens, Athens, Greece.
³ Institute of Infection, Immunity and Inflammation, University of Glasgow School of Medicine, Glasgow, UK.
⁴ University Research Institute of Maternal and Child Health and Precision Medicine, National and Kapodistrian University of Athens, Athens, Greece.
⁵ Department of Biological Chemistry, National and Kapodistrian University of Athens, Athens, Greece.
⁶ First Department of Propaedeutic and Internal Medicine and Joint Academic Rheumatology Program, National and Kapodistrian University of Athens, Athens, Greece psfikakis@med.uoa.gr.

Abstract

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.

Keywords: Arthritis; Arthritis, Rheumatoid; Glucocorticoids.

MeSH terms

Adrenocorticotropic Hormone / metabolism
Adrenocorticotropic Hormone / pharmacology
Arthritis, Rheumatoid* / drug therapy
COVID-19*
Humans
Hydrocortisone / metabolism
Prospective Studies

Substances

Hydrocortisone
Adrenocorticotropic Hormone

Associated data

ClinicalTrials.gov/NCT05671627