Smith P J, Brook C G, Rivier J, Vale W, Thorner M O
Clin Endocrinol (Oxf). 1986 Jul;25(1):35-44. doi: 10.1111/j.1365-2265.1986.tb03593.x.
We have treated five GH-deficient prepubertal children (4 M, 1 F) with GH releasing hormone 1-40 (GHRH1-40) in two dosage regimens over 9 months. Profiles of serum GH concentrations were obtained over 24 hours before treatment and nocturnal profiles were obtained serially throughout the study. GHRH was administered subcutaneously at night for four pulses using 1 microgram/kg/pulse in the first 3 months and 2 micrograms/kg/pulse for a further 6 months. All subjects demonstrated pituitary responsiveness to i.v. GHRH before treatment and at 3 and 6 months. GH secretion was induced in a pulsatile fashion in response to subcutaneous GHRH in three children from the first night of treatment. A self priming effect to successive GHRH pulses was evident and the response augmented with time and with the higher dose regimen. The growth velocity of these three children increased from a mean of 3.7 cm/year (range 3.7-3.8) before treatment to 5.5 cm/year (range 4.1-7.2) over the first 3 months and to 7.2 cm/year (range 4.8-9.2) over the following 6 months. In one subject entrainment of GH secretion to GHRH did not occur until the higher dose regimen and this was associated with a modest increase in growth velocity. One subject did not respond to treatment. Pulsatile administration of GHRH1-40 is effective in inducing GH secretion and promoting growth acceleration in some children with idiopathic GH deficiency. The optimal dose and mode of administration of GHRH have yet to be established.
我们采用两种剂量方案,用生长激素释放激素1 - 40(GHRH1 - 40)对5名青春期前生长激素缺乏的儿童(4名男性,1名女性)进行了为期9个月的治疗。在治疗前获取了24小时的血清生长激素浓度曲线,并在整个研究过程中连续获取夜间曲线。在前3个月,以1微克/千克/脉冲的剂量,于夜间皮下注射GHRH,共4个脉冲;在接下来的6个月中,剂量增加至2微克/千克/脉冲。所有受试者在治疗前、治疗3个月和6个月时均表现出垂体对静脉注射GHRH的反应性。从治疗的第一晚开始,3名儿童对皮下注射GHRH以脉冲方式诱导生长激素分泌。对连续的GHRH脉冲存在自我启动效应,且随着时间推移和更高剂量方案,反应增强。这3名儿童的生长速度从治疗前的平均3.7厘米/年(范围3.7 - 3.8)增加到前3个月的5.5厘米/年(范围4.1 - 7.2),并在接下来的6个月中增加到7.2厘米/年(范围4.8 - 9.2)。在1名受试者中,直到采用更高剂量方案才出现生长激素分泌与GHRH同步,且这与生长速度的适度增加相关。1名受试者对治疗无反应。脉冲式给予GHRH1 - 40对一些特发性生长激素缺乏儿童有效,可诱导生长激素分泌并促进生长加速。GHRH的最佳剂量和给药方式尚未确定。