Choudhury Sirazum, Tan Tricia, Lazarus Katharine, Meeran Karim
Endocrinology and Investigative Medicine, Department of Metabolism, Digestion and Reproduction, Imperial College London, Commonwealth Building, London, UK.
Department of Endocrinology, Imperial College Healthcare NHS Trust, London, UK.
Endocr Connect. 2021 Feb;10(2):R66-R76. doi: 10.1530/EC-20-0473.
The introduction of adrenocortical extract in 1930 improved the life expectancy of hyhpoadrenal patients, with further increases seen after the introduction of cortisone acetate from 1948. Most patients are now treated with synthetic hydrocortisone, and incremental advances have been made with optimisation of daily dosing and the introduction of multidose regimens. There remains a significant mortality gap between individuals with treated hypoadrenalism and the general population. It is unclear whether this gap is a result of glucocorticoid over-replacement, under-replacement or loss of the circadian and ultradian rhythm of cortisol secretion, with the risk of detrimental excess glucocorticoid exposure at later times in the day. The way forwards will involve replacement of the diurnal cortisol rhythm with better glucocorticoid replacement regimens. The steroid profile produced by both prednisolone and dual-release hydrocortisone (Plenadren), provide a smoother glucocorticoid profile of cortisol than standard oral multidose regimens of hydrocortisone and cortisone acetate. The individualisation of prednisolone doses and lower bioavailability of Plenadren offer reductions in total steroid exposure. Although there is emerging evidence of both treatments offering better cardiometabolic outcomes than standard glucocorticoid replacement regimens, there is a paucity of evidence involving very low dose prednisolone (2-4 mg daily) compared to the larger doses (~7.5 mg) historically used. Data from upcoming clinical studies on prednisolone will therefore be of key importance in informing future practice.
1930年肾上腺皮质提取物的引入提高了肾上腺功能减退患者的预期寿命，1948年醋酸可的松引入后预期寿命进一步提高。现在大多数患者接受合成氢化可的松治疗，在优化每日剂量和引入多剂量方案方面取得了渐进式进展。接受治疗的肾上腺功能减退患者与普通人群之间仍存在显著的死亡率差距。目前尚不清楚这种差距是由于糖皮质激素替代过量、替代不足还是皮质醇分泌的昼夜节律和超昼夜节律丧失，导致在一天晚些时候有有害的糖皮质激素过量暴露风险。未来的方向将涉及用更好的糖皮质激素替代方案来替代昼夜皮质醇节律。泼尼松龙和双相释放氢化可的松（普乐可复）产生的类固醇谱比氢化可的松和醋酸可的松的标准口服多剂量方案提供了更平稳的皮质醇糖皮质激素谱。泼尼松龙剂量的个体化和普乐可复较低的生物利用度降低了总类固醇暴露量。尽管越来越多的证据表明，这两种治疗方法比标准糖皮质激素替代方案能提供更好的心脏代谢结果，但与历史上使用的较大剂量（约7.5毫克）相比，涉及极低剂量泼尼松龙（每日2 - 4毫克）的证据很少。因此，即将开展的关于泼尼松龙的临床研究数据对于指导未来的实践至关重要。
