类风湿关节炎中皮质醇的日间分泌与治疗反应预测：一项 6 个月的真实前瞻性队列研究。

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

机构信息

First Department of Propaedeutic and Internal Medicine, Endocrinology Unit, National and Kapodistrian University of Athens, Athens, Greece.

First Department of Propaedeutic and Internal Medicine and Joint Academic Rheumatology Program, National and Kapodistrian University of Athens, Athens, Greece.

出版信息

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

DOI:10.1136/rmdopen-2023-003575

PMID:38233075

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10806498/

Abstract

OBJECTIVES

A reduced adrenal reserve-associated cortisol production relative to the enhanced needs of chronic inflammation () 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.

摘要

目的

与慢性炎症的增强需求相比，类风湿关节炎（RA）患者的肾上腺储备相关皮质醇产生减少。我们研究了在开始或升级治疗后，活动期 RA 患者日间皮质醇测量值对治疗反应预测的可能临床价值。

方法

通过电化学发光免疫分析法在 28 例中度/高度活跃的 RA 患者以及治疗开始或升级后 3 个月和 6 个月时评估日间皮质醇生成（测量时间：08-12:00/18:00-22:00）。28 例 COVID-19 患者和 28 名年龄匹配的健康个体（HC）作为对照。

结果

尽管 RA 患者的血清 C 反应蛋白（CRP）水平高 12 倍，且低于 COVID-19 患者（曲线下面积：RA：87.0±37.6 vs COVID-19：146.7±14.3，p<0.001），但 RA 患者的唾液日间皮质醇生成与 HC 相似，且 CRP 水平相似。此外，在 28 例 RA 患者中有 15 例在基线时存在明显的皮质醇昼夜节律紊乱，而在 28 例 HC 和 COVID-19 患者中分别有 4 例和 20 例。在 6 个月时，有 16 例 RA 患者达到了最小疾病活动度（MDA）。尽管基线时的人口统计学和临床特征相似，但与 MDA 患者相比，非 MDA 患者的基线早晨皮质醇较低，促肾上腺皮质激素（ACTH）水平较高（皮质醇：10.9±4.0 vs 18.4±8.2 nmol/L，p=0.005 和 ACTH：4.8±3.3 vs 2.4±0.4 pmol/L，p=0.047）。基线早晨皮质醇<13.9 nmol/L 可预测 6 个月时非 MDA（75%敏感性，92%特异性，p=0.006）。前瞻性测量显示，从基线到 3 个月和 6 个月，个体日间皮质醇生成基本保持不变。