超生理剂量氢化可的松替换治疗改变肾上腺皮质功能减退症患者的神经元处理、情绪模糊、情感和疲劳：PULSES 试验。
Ultradian hydrocortisone replacement alters neuronal processing, emotional ambiguity, affect and fatigue in adrenal insufficiency: The PULSES trial.
机构信息
Laboratories of Integrative Neuroscience and Endocrinology, Bristol Medical School, University of Bristol, Bristol, UK.
University Hospital Bristol and Weston NHS Foundation Trust, Bristol, UK.
出版信息
J Intern Med. 2024 Jan;295(1):51-67. doi: 10.1111/joim.13721. Epub 2023 Oct 19.
BACKGROUND
Primary adrenal insufficiency (PAI) mortality and morbidity remain unacceptably high, possibly arising as glucocorticoid replacement does not replicate natural physiology. A pulsatile subcutaneous pump can closely replicate cortisol's circadian and ultradian rhythm.
OBJECTIVES
To assess the effect of pump therapy on quality of life, mood, functional neuroimaging, behavioural/cognitive responses, sleep and metabolism.
METHODS
A 6-week randomised, crossover, double-blinded and placebo-controlled feasibility study of usual dose hydrocortisone in PAI administered as either pulsed subcutaneous or standard care in Bristol, United Kingdom (ISRCTN67193733). Participants were stratified by adrenal insufficiency type. All participants who received study drugs are included in the analysis. The primary outcome, the facial expression recognition task (FERT), occurred at week 6.
RESULTS
Between December 2014 and 2017, 22 participants were recruited - 20 completed both arms, and 21 were analysed. The pump was well-tolerated. No change was seen in the FERT primary outcome; however, there were subjective improvements in fatigue and mood. Additionally, functional magnetic resonance imaging revealed differential neural processing to emotional cues and visual stimulation. Region of interest analysis identified the left amygdala and insula, key glucocorticoid-sensitive regions involved in emotional ambiguity. FERT post hoc analysis confirmed this response. There were four serious adverse events (AE): three intercurrent illnesses requiring hospitalisation (1/3, 33.3% pump) and a planned procedure (1/1, 100% pump). There was a small number of expected AEs: infusion site bruising/itching (3/5, 60% pump), intercurrent illness requiring extra (3/7, 42% pump) and no extra (4/6, 66% pump) steroid.
CONCLUSIONS
These findings support the administration of hormone therapy that mimics physiology.
背景
原发性肾上腺功能不全（PAI）的死亡率和发病率仍然高得令人无法接受，这可能是由于糖皮质激素替代治疗未能复制自然生理机能。脉冲皮下泵可以紧密复制皮质醇的昼夜节律和超昼夜节律。
目的
评估泵治疗对生活质量、情绪、功能神经影像学、行为/认知反应、睡眠和新陈代谢的影响。
方法
在英国布里斯托尔进行了一项为期 6 周的随机、交叉、双盲、安慰剂对照的可行性研究，研究对象为接受常规剂量氢化可的松治疗的 PAI 患者，这些患者接受的治疗为脉冲皮下给药或标准治疗。根据肾上腺功能不全的类型对参与者进行分层。所有接受研究药物治疗的参与者均纳入分析。主要结局指标为面部表情识别任务（FERT），发生在第 6 周。
结果
2014 年 12 月至 2017 年期间，共招募了 22 名参与者-20 名参与者完成了两项研究，21 名参与者被纳入分析。泵治疗耐受性良好。FERT 主要结局无变化；然而，疲劳和情绪有主观改善。此外，功能磁共振成像显示情绪线索和视觉刺激的神经处理存在差异。感兴趣区域分析确定了左杏仁核和岛叶，这些是涉及情绪模糊性的关键糖皮质激素敏感区域。FERT 事后分析证实了这一反应。有 4 例严重不良事件（AE）：3 例需要住院治疗的并发疾病（1/3，33.3%的泵）和 1 例计划程序（1/1，100%的泵）。还有一些预期的 AE：输注部位瘀伤/瘙痒（3/5，60%的泵），并发疾病需要额外（3/7，42%的泵）和不需要额外（4/6，66%的泵）类固醇。
结论
这些发现支持使用模拟生理机能的激素治疗。
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