Jaffe C A, Pan W, Brown M B, DeMott-Friberg R, Barkan A L
Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Michigan Medical Center, University of Michigan, Ann Arbor, Michigan 48109, USA.
J Clin Endocrinol Metab. 2001 Sep;86(9):4364-70. doi: 10.1210/jcem.86.9.7840.
GH hypersecretion is a hallmark of acromegaly. It is unknown whether the secretory activity of somatotroph adenoma is autonomous or is still governed by central or peripheral mechanisms. In this study we investigated whether GH secretion in acromegaly 1) has a reproducible circadian pattern and 2) is inhibited by exogenous IGF-I. Eleven patients with newly diagnosed acromegaly were studied in 2 protocols. In protocol 1, peripheral blood was sampled every 10 min for 48 h in 6 patients for the determination of concordance between 24-h GH profiles. There was no significant day to day variability in mean 24-h output. There was, however, a significant time effect, and the 24-h GH secretion pattern was maintained between days. In protocol 2, 5 patients were sampled for GH every 10 min twice, once during infusion of normal saline and once during iv infusion of recombinant human IGF-I (10 microg/kg x h). The recombinant human IGF-I infusion increased plasma IGF-I to approximately 230% of the baseline concentration. This resulted in GH suppression (4220 +/- 1950 vs. 3223 +/- 1472 microg/liter.min; P = 0.001), but did not alter GH secretion pattern. There were highly significant cross-correlations for 10 of the 11 of the subjects in the two protocols when the lag was 0 min. By harmonic analysis, nocturnal augmentation of GH was maintained, and maximum daily GH occurred at approximately 2300 h. These data demonstrate that the pattern of GH secretion in acromegaly is not random, but is highly preserved with 24-h periodicity. In addition, negative feedback regulation by IGF-I is preserved, although the degree of negative feedback is grossly attenuated. Thus, secretory activity of somatotroph adenomas is not autonomous or haphazard, but is still subject to both feedback and feedforward regulatory mechanisms.
生长激素分泌过多是肢端肥大症的一个标志。目前尚不清楚生长激素腺瘤的分泌活动是自主性的，还是仍受中枢或外周机制的调控。在本研究中，我们调查了肢端肥大症患者的生长激素分泌情况：1）是否具有可重复的昼夜节律模式；2）是否受外源性胰岛素样生长因子-I（IGF-I）抑制。11例新诊断的肢端肥大症患者参与了2项研究方案。在方案1中，6例患者每10分钟采集一次外周血，共采集48小时，以确定24小时生长激素谱之间的一致性。24小时平均分泌量无显著的每日变化。然而，存在显著的时间效应，且24小时生长激素分泌模式在不同日期之间保持稳定。在方案2中，5例患者每10分钟采集一次生长激素样本，共采集两次，一次在输注生理盐水期间，一次在静脉输注重组人生长激素-I（10微克/千克·小时）期间。重组人生长激素-I输注使血浆IGF-I升高至基线浓度的约230%。这导致生长激素分泌受到抑制（4220±1950对3223±1472微克/升·分钟；P = 0.001），但未改变生长激素分泌模式。当延迟为0分钟时，两项研究方案中11名受试者中的10名存在高度显著的交叉相关性。通过谐波分析，生长激素的夜间分泌增加得以维持，且每日生长激素分泌峰值出现在约23:00。这些数据表明，肢端肥大症患者的生长激素分泌模式并非随机，而是以24小时周期高度保持稳定。此外，尽管负反馈程度明显减弱，但IGF-I的负反馈调节仍然存在。因此，生长激素腺瘤的分泌活动并非自主性或随意性的，而是仍受反馈和前馈调节机制的影响。
