Institute of Genetic Medicine (E.H.G., K.M., A.L.M., P.P., R.Q., S.H.S.P.), Newcastle University, Newcastle upon Tyne NE1 3BZ, United Kingdom; the Endocrine Unit (E.H.G., A.L.M., P.P., S.G.B., R.A.J., R.Q., S.H.S.P.), Royal Victoria Infirmary, Newcastle upon Tyne NE1 4LP, United Kingdom; the Centre for Endocrinology, Diabetes, and Metabolism (B.A.H., W.A.), University of Birmingham, Birmingham B15 2TT, United Kingdom; and RSR Ltd (S.C., J.F.), FIRS Laboratories, Cardiff CF4 5DU, United Kingdom.
J Clin Endocrinol Metab. 2014 Jan;99(1):111-8. doi: 10.1210/jc.2013-2449. Epub 2013 Dec 20.
Despite lifelong steroid hormone replacement, there is excess morbidity and mortality associated with autoimmune Addison's disease. In health, adrenocortical cells undergo continuous self-renewal from a population of subcapsular progenitor cells, under the influence of ACTH, suggesting a therapeutic possibility.
We aimed to determine whether tetracosactide (synthetic ACTH1-24) could revive adrenal steroidogenic function in autoimmune Addison's disease.
DESIGN, SETTING, AND PATIENTS: Thirteen patients (aged 16-65 y) with established autoimmune Addison's disease for more than 1 year were recruited at the Newcastle University Clinical Research Facility.
The intervention included a 20-week study of regular sc tetracosactide (ACTH1-24) therapy.
Serum and urine corticosteroids were measured during medication withdrawal at baseline and every 5 weeks during the study.
Serum cortisol levels remained less than 100 nmol/L in 11 of 13 participants throughout the study. However, two women achieved peak serum cortisol concentrations greater than 400 nmol/L after 10 and 29 weeks of tetracosactide therapy, respectively, allowing withdrawal of corticosteroid replacement. Concurrently, urine glucocorticoid and mineralocorticoid metabolite excretion increased from subnormal to above the median of healthy controls. One of these responders remains well with improving peak serum cortisol (672 nmol/L) 28 months after stopping all treatments. The other responder showed a gradual reduction in serum cortisol and aldosterone over time, and steroid therapy was recommenced after a 28-week period without glucocorticoid replacement.
This is the first study to demonstrate that established autoimmune Addison's disease is amenable to a regenerative medicine therapy approach.
尽管终生接受类固醇激素替代治疗，但自身免疫性艾迪生病仍与较高的发病率和死亡率相关。在健康状态下，肾上腺皮质细胞在 ACTH 的影响下，从包膜下祖细胞群体中不断进行自我更新，这提示了一种治疗的可能性。
我们旨在确定廿四肽促皮质素（合成 ACTH1-24）是否能恢复自身免疫性艾迪生病中的肾上腺皮质甾体生成功能。
设计、地点和患者：13 例（年龄 16-65 岁）患有明确的自身免疫性艾迪生病超过 1 年的患者在纽卡斯尔大学临床研究中心被招募。
该干预包括 20 周的常规 sc 廿四肽促皮质素（ACTH1-24）治疗研究。
在基线时和研究期间每 5 周停用药物时测量血清和尿皮质类固醇。
13 例患者中有 11 例在整个研究期间血清皮质醇水平一直低于 100 nmol/L。然而，2 例女性在接受廿四肽促皮质素治疗 10 和 29 周后分别达到了大于 400 nmol/L 的峰值血清皮质醇浓度，从而可以停用皮质类固醇替代治疗。同时，尿糖皮质激素和盐皮质激素代谢产物的排泄从低于正常水平增加到超过健康对照的中位数。其中 1 例缓解者在停用所有治疗 28 个月后仍保持良好状态，其峰值血清皮质醇（672 nmol/L）增加。另 1 例缓解者的血清皮质醇和醛固酮随时间逐渐降低，在停用皮质激素替代治疗 28 周后重新开始使用类固醇治疗。
这是第一项表明已确立的自身免疫性艾迪生病可采用再生医学治疗方法的研究。
