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慢性肾功能衰竭及肾移植后青春期前男孩生长激素分泌与清除的改变。慢性肾功能衰竭青春期发育合作研究组

Alterations in growth hormone secretion and clearance in peripubertal boys with chronic renal failure and after renal transplantation. Cooperative Study Group of Pubertal development in Chronic Renal Failure.

作者信息

Schaefer F, Veldhuis J D, Stanhope R, Jones J, Schärer K

机构信息

Division of Pediatric Nephrology, University Children's Hospital, Heidelberg, Germany.

出版信息

J Clin Endocrinol Metab. 1994 Jun;78(6):1298-306. doi: 10.1210/jcem.78.6.8200929.

Abstract

To elucidate the endocrine mechanisms underlying the pubertal growth failure observed in patients with chronic renal failure (CRF), we used deconvolution analysis to estimate the rates of GH secretion and elimination in nighttime plasma GH profiles of peripubertal boys with CRF and after renal transplantation (Tx). Forty-three boys with advanced CRF (conservative treatment with glomerular filtration rate < 25 mL/min.1.73 m2 or dialysis; CT/D group), 38 boys after Tx, and 40 healthy control boys were studied. The estimated plasma GH half-life (mean +/- SEM) was significantly higher (P < 0.05) in CRF (25 +/- 1.8 min) than in Tx patients (21 +/- 1.6 min) and controls (20 +/- 0.5 min). In the pre- and early pubertal CT/D boys, the calculated GH secretion rate was low normal or reduced when expressed in absolute numbers or normalized per unit distribution volume or body surface. In late puberty, whereas body surface-corrected GH secretion was double the prepubertal value in normal boys (389 +/- 56 vs. 868 +/- 113 micrograms/m2.11 h; P < 0.01), it did not differ significantly from the prepubertal rate in CT/D boys (281 +/- 59 vs. 389 +/- 56 micrograms/m2.11 h). GH hyposecretion resulted from a decrease in the mass of GH released within each burst, whereas burst frequency was unchanged. In the Tx group, GH secretion rates were significantly reduced in the prepubertal (221 +/- 39 micrograms/m2.11 h; P < 0.05) and late pubertal period (266 +/- 64 micrograms/m2.11 h; P < 0.01). The mass of hormone secreted per burst was significantly reduced at each pubertal stage, whereas GH secretory burst frequency tended to be increased (significant in prepubertal group, P < 0.05). The GH secretion rate was positively correlated with plasma testosterone levels (r = 0.58; P < 0.0001) in controls, but not in CT/D or Tx patients. GH secretion rates were lower than expected at each level of plasma testosterone in both patient groups except CT/D boys with plasma testosterone below 0.9 nmol/L. In the Tx group, GH secretion rate was positively correlated with relative height (r = 0.31; P < 0.05). The dosage of corticosteroids administered for immunosuppression was negatively correlated with GH burst mass (r = -0.42; P < 0.01) and GH secretion rate (r = -0.29; P = 0.08) and positively correlated with GH burst frequency (r = 0.49; P < 0.01). We conclude that in peripubertal boys with CRF, a state of GH hyposecretion is associated with an increase in the apparent plasma half-life of GH.(ABSTRACT TRUNCATED AT 400 WORDS)

摘要

为阐明慢性肾衰竭(CRF)患者青春期生长发育迟缓潜在的内分泌机制,我们采用去卷积分析方法,估算青春期前后患CRF男孩及肾移植(Tx)后男孩夜间血浆生长激素(GH)谱中GH的分泌率和清除率。研究对象包括43例晚期CRF男孩(采用保守治疗,肾小球滤过率<25 mL/min·1.73 m²或接受透析;CT/D组)、38例Tx后男孩以及40例健康对照男孩。CRF组血浆GH半衰期(均值±标准误)显著高于Tx患者组(25±1.8分钟)和对照组(20±0.5分钟)(P<0.05)。在青春期前及青春期早期的CT/D组男孩中,以绝对值或按单位分布容积或体表面积标准化后计算的GH分泌率处于低正常水平或降低。青春期后期,正常男孩经体表面积校正的GH分泌量是青春期前值的两倍(389±56 vs. 868±113微克/m²·11小时;P<0.01),而CT/D组男孩此值与青春期前速率无显著差异(281±59 vs. 389±56微克/m²·11小时)。GH分泌不足是由于每次脉冲释放的GH量减少,而脉冲频率未变。Tx组中,青春期前(221±39微克/m²·11小时;P<0.05)和青春期后期(266±64微克/m²·11小时;P<0.01)的GH分泌率均显著降低。每个青春期阶段每次脉冲分泌的激素量均显著减少,而GH分泌脉冲频率有增加趋势(青春期前组显著,P<0.05)。对照组中GH分泌率与血浆睾酮水平呈正相关(r = 0.58;P<0.0001),但CT/D组或Tx患者组并非如此。除血浆睾酮低于0.9 nmol/L的CT/D组男孩外,两个患者组在各血浆睾酮水平下的GH分泌率均低于预期。在Tx组,GH分泌率与相对身高呈正相关(r = 0.31;P<0.05)。用于免疫抑制的皮质类固醇剂量与GH脉冲量(r = -0.42;P<0.01)和GH分泌率(r = -0.29;P = 0.08)呈负相关,与GH脉冲频率呈正相关(r = 0.49;P<0.01)。我们得出结论,青春期前后患CRF的男孩中,GH分泌不足状态与GH在血浆中的表观半衰期延长有关。(摘要截短于400字)

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