Department of Neurology, Leiden University Medical Centre, Leiden, The Netherlands.
Am J Physiol Endocrinol Metab. 2011 Jun;300(6):E1069-75. doi: 10.1152/ajpendo.00623.2010. Epub 2011 Mar 29.
Hypocretin deficiency causes narcolepsy and may affect neuroendocrine systems and body composition. Additionally, growth hormone (GH) alterations my influence weight in narcolepsy. Symptoms can be treated effectively with sodium oxybate (SXB; γ-hydroxybutyrate) in many patients. This study compared growth hormone secretion in patients and matched controls and established the effect of SXB administration on GH and sleep in both groups. Eight male hypocretin-deficient patients with narcolepsy and cataplexy and eight controls matched for sex, age, BMI, waist-to-hip ratio, and fat percentage were enrolled. Blood was sampled before and on the 5th day of SXB administration. SXB was taken two times 3 g/night for 5 consecutive nights. Both groups underwent 24-h blood sampling at 10-min intervals for measurement of GH concentrations. The GH concentration time series were analyzed with AutoDecon and approximate entropy (ApEn). Basal and pulsatile GH secretion, pulse regularity, and frequency, as well as ApEn values, were similar in patients and controls. Administration of SXB caused a significant increase in total 24-h GH secretion rate in narcolepsy patients, but not in controls. After SXB, slow-wave sleep (SWS) and, importantly, the cross-correlation between GH levels and SWS more than doubled in both groups. In conclusion, SXB leads to a consistent increase in nocturnal GH secretion and strengthens the temporal relation between GH secretion and SWS. These data suggest that SXB may alter somatotropic tone in addition to its consolidating effect on nighttime sleep in narcolepsy. This could explain the suggested nonsleep effects of SXB, including body weight reduction.
下丘脑分泌素缺乏会导致发作性睡病,并可能影响神经内分泌系统和身体成分。此外,生长激素(GH)的改变可能会影响发作性睡病患者的体重。在许多患者中,γ-羟基丁酸(SXB)可以有效治疗症状。本研究比较了患者和匹配对照组的生长激素分泌情况,并确定了 SXB 给药对两组患者 GH 和睡眠的影响。纳入 8 名男性下丘脑分泌素缺乏型发作性睡病伴猝倒患者和 8 名性别、年龄、BMI、腰臀比和脂肪百分比匹配的对照组。在 SXB 给药前和第 5 天采集血液样本。SXB 每晚连续 5 天服用 2 次,每次 3 克。两组均在 24 小时内以 10 分钟为间隔采集血液样本,以测量 GH 浓度。使用 AutoDecon 和近似熵(ApEn)分析 GH 浓度时间序列。患者和对照组的基础和脉冲 GH 分泌、脉冲规律性和频率以及 ApEn 值相似。SXB 给药导致发作性睡病患者 24 小时总 GH 分泌率显著增加,但对照组没有。SXB 后,两组的慢波睡眠(SWS),特别是 GH 水平与 SWS 之间的交叉相关性显著增加。总之,SXB 导致夜间 GH 分泌持续增加,并增强了 GH 分泌与 SWS 之间的时间关系。这些数据表明,SXB 除了对发作性睡病的夜间睡眠有巩固作用外,还可能改变躯体激素的张力。这可以解释 SXB 的非睡眠作用,包括体重减轻。