Kletter G B, Rolfes-Curl A, Goodpasture J C, Solish S B, Scott L, Henzl M R, Beitins I Z
Department of Pediatrics, University of Michigan, Ann Arbor, USA.
J Pediatr Endocrinol Metab. 1996 Jan-Feb;9(1):9-19. doi: 10.1515/jpem.1996.9.1.9.
To determine the usefulness of a GnRH agonist analog as a diagnostic test to distinguish between constitutional delay of growth (CGD) in boys with Tanner stage I of sexual development and patients with hypogonadotropic hypogonadism (HH), we evaluated six boys (mean age 15 yr 4 m) and five HH patients (mean age 20 yr 4 m). In addition, 20 normal healthy men aged 21 yr to 50 yr received either nafarelin or GnRH followed two weeks later by the other test in order to compare the efficacy of each of these tests and to evaluate the optimal sampling times for the nafarelin test. All subjects were healthy, and had not received hormonal replacement for at least 2 months prior to enrollment in the study. Each man had four baseline blood samples before and at timed intervals following the administration of either GnRH or nafarelin. Each of the patients had blood withdrawn every 15 min during 12 h overnight followed by a single s.c. injection of nafarelin (1 microgram(s)/kg up to 100 microgram(s)), except two HH patients who did not have an overnight study. Blood samples were obtained at timed intervals for 24 h. LH, FSH, T and E2 were measured by RIA. Baseline concentrations of plasma LH, FSH and T were similar before the administration of either GnRH or nafarelin in the group of normal men. Peak stimulation of plasma LH, FSH and T released by nafarelin was significantly higher, and it took a longer time to reach the peak maximum, than after GnRH (p < 0.001). Mean nocturnal LH was 5.5 +/- 0.9 IU/I for the CGD group, and 2.7 +/- 0.7 IU/I for HH (p < 0.02). Mean nocturnal FSH was 5.1 +/- 1.0 and 2.5 +/- 0.2 IU/I whereas mean nocturnal T concentrations were 4.2 +/- 0.8 and 0.7 +/- 0.2 nmol/I (CGD vs HH, respectively, p < 0.02). Peak LH responses to nafarelin were 36.9 +/- 8.9 IU/I for the CGD group, and 7.0 +/- 2.0 IU/I for the HH group (p < 0.001). Peak FSH released by nafarelin was 14.2 +/- 2.4 IU/I for the CGD group and 4.8 +/- 2.0 IU/I for the HH group (p < 0.02). Peak T was reached 24 h following nafarelin injection and was 5.7 +/- 1.7 nmol/I for the CGD group and 0.3 +/- 0.2 nmol/I for the HH group (p < 0.001). The results obtained indicate that in early stages of puberty (before detectable changes of sexual maturation) the nafarelin test, with measurements of LH, FSH and T in blood or in urine, is superior to and more practical than overnight hormonal estimates to clearly distinguish CGD from HH.
为了确定促性腺激素释放激素（GnRH）激动剂类似物作为一种诊断测试手段，用于区分性发育处于坦纳I期的男孩的体质性生长延迟（CGD）和低促性腺激素性性腺功能减退（HH）患者的有效性，我们评估了6名男孩（平均年龄15岁4个月）和5名HH患者（平均年龄20岁4个月）。此外，20名年龄在21岁至50岁之间的正常健康男性分别接受了那法瑞林或GnRH治疗，两周后再接受另一种测试，以便比较这两种测试的效果，并评估那法瑞林测试的最佳采样时间。所有受试者均健康，且在参加研究前至少2个月未接受过激素替代治疗。每个男性在给予GnRH或那法瑞林之前及之后的特定时间间隔采集4份基线血样。除了2名未进行夜间研究的HH患者外，其他患者在夜间12小时内每隔15分钟采血一次，随后皮下注射一次那法瑞林（1微克/千克，最大剂量100微克）。在24小时内按特定时间间隔采集血样。采用放射免疫分析法（RIA）测定促黄体生成素（LH）、促卵泡生成素（FSH）、睾酮（T）和雌二醇（E2）。在正常男性组中，给予GnRH或那法瑞林之前，血浆LH、FSH和T的基线浓度相似。那法瑞林释放的血浆LH、FSH和T的峰值刺激明显更高，且达到峰值的时间比GnRH给药后更长（p<0.001）。CGD组夜间平均LH为5.5±0.9 IU/I，HH组为2.7±0.7 IU/I（p<0.02）。夜间平均FSH分别为5.1±1.0和2.5±0.2 IU/I，而夜间平均T浓度分别为4.2±0.8和0.7±0.2 nmol/I（CGD组与HH组相比，p<0.02）。CGD组对那法瑞林的LH峰值反应为36.9±8.9 IU/I，HH组为7.0±2.0 IU/I（p<0.001）。那法瑞林释放的FSH峰值，CGD组为14.2±2.4 IU/I，HH组为4.8±2.0 IU/I（p<0.02）。那法瑞林注射后24小时达到T峰值，CGD组为5.7±1.7 nmol/I，HH组为0.3±0.2 nmol/I（p<0.001）。所得结果表明，在青春期早期（在可检测到性成熟变化之前），通过测定血液或尿液中的LH、FSH和T进行的那法瑞林测试，在明确区分CGD和HH方面优于夜间激素评估且更具实用性。
