Masi A T, Josipović D B, Jefferson W E
Semin Arthritis Rheum. 1984 Aug;14(1):1-23. doi: 10.1016/0049-0172(84)90005-2.
Using GLC, multiple adrenal corticosteroid urinary metabolites, including androgenic-anabolic, glucocorticoid, pregnanediol, and pregnanetriol, were measured in eight ambulatory female RA patients and eight matched normal control subjects on baseline, ACTH-, and metyrapone-stimulation days under carefully monitored clinical research center protocol. Neither group had been treated previously with any steroid hormones. The 11-deoxy-17-KS metabolites, derived from adrenal androgenic-anabolic steroids, and comprising androsterone, etiocholanolone, and DHA, were significantly lower in RA patients on baseline (P less than .001), ACTH (P less than .005)-, and metyrapone (P less than .02)-stimulation days. To the contrary, the 11-oxy-17-KS metabolites, derived mainly from glucocorticoids, showed some lowered excretion at baseline (P less than .05), but none on ACTH- or metyrapone-stimulation. RA patients had lower tetrahydrocortisone (P less than .001) and tetrahydro-11-deoxycortisol (P less than .01) excretion at baseline, but not during ACTH- or metyrapone-stimulation, than control subjects. Pregnanetriol excretion was lower (P less than .005) in RA patients than control subjects only during ACTH-stimulation. No difference was found between groups in tetrahydrocortisol or pregnanediol excretion on any day studied. Under conditions of oral metyrapone administration (750 mg every four hours for seven doses) each control subject increased their DHA excretion, but no RA patient showed an increase over baseline excretion (P less than .02). Except for 11-deoxy-17-KS, no difference was found in the other metabolites studied during metyrapone stimulation, ie, pregnanediol, pregnanetriol, tetrahydro-11-deoxycortisol, and tetrahydrocortisol. The 24-hour oral metyrapone test provided a greater stimulus to total 11-deoxy-17-KS excretion than an eight-hour intravenous ACTH test in control and particularly RA (P less than .01) subjects even though the DHA excretion decreased in the RA groups. Our findings of lower adrenal androgenic-anabolic metabolite excretion in female RA patients than normal matched control subjects under various conditions and other supportive androgenic hormone and metabolite studies reviewed in the English reports suggest an abnormality of adrenal androgen synthesis or metabolism in RA, whether it be a primary predisposing or secondary factor in disease. The recognized female sex preponderance and age-specific patterns of occurrence of RA are consistent with adrenal androgenic function in adrenarche, adrenopause, and later changes in aging. Metabolite excretion patterns at baseline, ACTH-, and metyrapone- stimulation indicate the greatest relative
采用气相色谱法，在严密监测的临床研究中心方案下，于基线期、促肾上腺皮质激素（ACTH）刺激期和甲吡酮刺激期，对8名非卧床女性类风湿关节炎（RA）患者和8名匹配的正常对照受试者的多种肾上腺皮质类固醇尿代谢产物进行了测定，这些代谢产物包括雄激素 - 同化类固醇、糖皮质激素、孕二醇和孕三醇。两组此前均未接受过任何类固醇激素治疗。源自肾上腺雄激素 - 同化类固醇、由雄酮、本胆烷醇酮和脱氢表雄酮（DHA）组成的11 - 脱氧 - 17 - 酮类固醇（11 - deoxy - 17 - KS）代谢产物，在基线期（P＜0.001）、ACTH刺激期（P＜0.005）和甲吡酮刺激期（P＜0.02），RA患者均显著低于正常对照。相反，主要源自糖皮质激素的11 - 氧代 - 17 - 酮类固醇（11 - oxy - 17 - KS）代谢产物，在基线期排泄量有所降低（P＜0.05），但在ACTH或甲吡酮刺激期无变化。与对照受试者相比，RA患者在基线期四氢皮质醇排泄量较低（P＜0.001），四氢 - 11 - 脱氧皮质醇排泄量较低（P＜0.01），但在ACTH或甲吡酮刺激期无差异。仅在ACTH刺激期，RA患者的孕三醇排泄量低于对照受试者（P＜0.005）。在研究的任何一天，两组间四氢皮质醇或孕二醇排泄量均未发现差异。口服甲吡酮（每4小时750 mg，共7剂）后，每个对照受试者的DHA排泄量均增加，但无RA患者的排泄量超过基线水平（P＜0.02）。除11 - 脱氧 - 17 - KS外，在甲吡酮刺激期间研究的其他代谢产物，即孕二醇、孕三醇、四氢 - 11 - 脱氧皮质醇和四氢皮质醇，两组间未发现差异。24小时口服甲吡酮试验比8小时静脉注射ACTH试验对总11 - 脱氧 - 17 - KS排泄的刺激更大，在对照受试者中尤其如此，在RA患者中也是如此（P＜0.01），尽管RA组的DHA排泄量有所下降。我们的研究发现，在各种条件下，女性RA患者肾上腺雄激素 - 同化代谢产物的排泄低于正常匹配对照受试者，以及英文报告中综述的其他支持性雄激素和代谢产物研究表明，RA患者存在肾上腺雄激素合成或代谢异常，无论其是疾病的主要易感因素还是次要因素。公认的RA女性性别优势和特定年龄发病模式与肾上腺在肾上腺初现、肾上腺功能减退及随后衰老变化中的雄激素功能一致。基线期、ACTH和甲吡酮刺激期的代谢产物排泄模式表明相对差异最大。
