Kanik K S, Chrousos G P, Schumacher H R, Crane M L, Yarboro C H, Wilder R L
Arthritis and Rheumatism Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
J Clin Endocrinol Metab. 2000 Apr;85(4):1461-6. doi: 10.1210/jcem.85.4.6534.
To determine whether alterations in adrenocortical function occur early in the development of inflammatory joint disease, we examined patients with new onset synovitis (<1 yr) prior to treatment with corticosteroids or other disease-modifying antirheumatic drugs. Thirty-two patients with new onset synovitis, including 15 fitting criteria for rheumatoid arthritis (RA), taking no medications, were referred for study by local rheumatologists; 32 age- and sex-matched healthy individuals were recruited as controls. Patients and controls had blood drawn under identical conditions between 0900 and 1100 h. Plasma ACTH, cortisol, dehydroepiandrosterone (DHEA), DHEA sulfate, free and total testosterone, erythrocyte sedimentation rate, C-reactive protein, and rheumatoid factor were measured. Compared with controls, patients had higher inflammatory indices (erythrocyte sedimentation rate, C-reactive protein) and lower basal morning levels of free testosterone (lower in males age > or =45 yr), but similar levels of ACTH, cortisol, DHEA, DHEA sulfate, and total testosterone. In addition, the positive correlations between ACTH-cortisol, ACTH-DHEA, and cortisol-DHEA, observed in the normal controls, were weakened or abolished in the patients (both total and RA subset). No positive relations between inflammatory indices and ACTH or cortisol were noted, yet an inverse correlation between these indices and DHEA and testosterone was observed. Moreover, a steeper age-associated decline in DHEA was observed in our cross-sectional sample of patients with new onset synovitis. We conclude that patients with synovitis (including those fitting criteria for RA) have adrenocortical hormone alterations within a year of disease onset. Paradoxically, these patients have no positive relation between indices of inflammation and ACTH or cortisol, but rather serum androgen levels are inversely correlated with these indices. In addition, the relations between ACTH, the classic stimulus of cortisol and adrenal androgens, and these hormones are weakened or abolished, whereas the negative relation between age and zona reticularis function is steeper than that of controls.
为了确定肾上腺皮质功能改变是否在炎症性关节疾病发展的早期出现，我们在患者使用皮质类固醇或其他改善病情的抗风湿药物治疗前，对新发滑膜炎（<1年）患者进行了检查。32例新发滑膜炎患者，包括15例符合类风湿关节炎（RA）标准且未服用任何药物的患者，由当地风湿病学家转诊进行研究；招募了32名年龄和性别匹配的健康个体作为对照。患者和对照在上午09:00至11:00之间的相同条件下采血。检测血浆促肾上腺皮质激素（ACTH）、皮质醇、脱氢表雄酮（DHEA）、硫酸脱氢表雄酮、游离睾酮和总睾酮、红细胞沉降率、C反应蛋白和类风湿因子。与对照组相比，患者具有更高的炎症指标（红细胞沉降率、C反应蛋白），且游离睾酮的基础早晨水平较低（年龄≥45岁的男性更低），但ACTH、皮质醇、DHEA、硫酸脱氢表雄酮和总睾酮水平相似。此外，在正常对照组中观察到的ACTH与皮质醇、ACTH与DHEA以及皮质醇与DHEA之间的正相关，在患者（总体和RA亚组）中减弱或消失。未发现炎症指标与ACTH或皮质醇之间存在正相关，但观察到这些指标与DHEA和睾酮之间存在负相关。此外，在我们的新发滑膜炎患者横断面样本中，观察到DHEA随年龄下降更为明显。我们得出结论，滑膜炎患者（包括符合RA标准的患者）在疾病发作一年内存在肾上腺皮质激素改变。矛盾的是，这些患者的炎症指标与ACTH或皮质醇之间没有正相关，而是血清雄激素水平与这些指标呈负相关。此外，ACTH（皮质醇和肾上腺雄激素的经典刺激物）与这些激素之间的关系减弱或消失，而年龄与网状带功能之间的负相关比对照组更为明显。
