van den Berg G, Frölich M, Veldhuis J D, Roelfsema F
Department of Endocrinology, University Hospital, Leiden, The Netherlands.
J Clin Endocrinol Metab. 1994 Dec;79(6):1706-15. doi: 10.1210/jcem.79.6.7989479.
GH secretion patterns were studied in 14 recently transsphenoidally operated patients by measuring GH concentrations in blood sampled every 10 min over 24 h with a highly sensitive time-resolved immuno-fluorescent assay. Plasma GH concentrations were analyzed with a discrete peak detection program (Cluster) and a multiparameter deconvolution technique. Diurnal variations were analyzed by cosinor analysis. Nine or 10 days after pituitary surgery all patients had a normal plasma insulin-like growth factor-I level, and GH levels were suppressed to below 1.25 micrograms/L in 13 patients and to 1.3 micrograms/L in 1 subject during an oral glucose tolerance test. As we found a highly significant difference in GH secretion between male and female controls, the results obtained in patients were compared with those in their gender- and age-matched controls. Patients with active acromegaly displayed a significantly higher number of deconvolution-estimated secretory bursts (31/24 h in males and 27/24 h in female patients). The estimated secretion rate per 24 h was 25 times greater in female acromegalics and 100 times greater in male acromegalics than that in the controls. In patients with active acromegaly, about 50% of the GH was secreted in a nonpulsatile fashion. In contrast, normal subjects and patients shortly after pituitary surgery secreted GH predominantly (> 99%) in a pulsatile manner. By deconvolution analysis, the mean plasma half-life of GH was 19.7 min in treated male patients and 19.5 min in treated female patients (P = NS vs. controls) estimated mean total GH production/day, 188 micrograms in males and 240 micrograms in females (P = NS vs. controls); number of secretory bursts/24 h, 19.3 in males and 21.9 in females (P = NS vs. controls). In addition, we could not establish any difference in pulse characteristics with Cluster analysis between surgically treated patients and their control subjects. The present data suggest that the basic abnormality of acromegaly resides in the pituitary gland rather than in the hypothalamus.
通过采用高灵敏度时间分辨免疫荧光分析法，每10分钟采集一次血样，测定24小时内的生长激素（GH）浓度，对14例近期接受经蝶窦手术的患者的GH分泌模式进行了研究。采用离散峰值检测程序（Cluster）和多参数反卷积技术分析血浆GH浓度。通过余弦分析昼夜变化。垂体手术后9或10天，所有患者的血浆胰岛素样生长因子-I水平均正常，在口服葡萄糖耐量试验期间，13例患者的GH水平被抑制至1.25微克/升以下，1例患者被抑制至1.3微克/升。由于我们发现男性和女性对照者的GH分泌存在高度显著差异，因此将患者的结果与其性别和年龄匹配的对照者的结果进行了比较。活动性肢端肥大症患者经反卷积估计的分泌脉冲数量显著更高（男性患者为31次/24小时，女性患者为27次/24小时）。女性肢端肥大症患者每24小时的估计分泌率比对照者高25倍，男性肢端肥大症患者比对照者高100倍。在活动性肢端肥大症患者中，约50%的GH以非脉冲方式分泌。相比之下，正常受试者和垂体手术后不久的患者主要以脉冲方式分泌GH（>99%）。通过反卷积分析，治疗后的男性患者GH的平均血浆半衰期为19.7分钟，治疗后的女性患者为19.5分钟（与对照者相比P=无显著性差异）；估计的GH每日总产生量，男性为188微克，女性为240微克（与对照者相比P=无显著性差异）；分泌脉冲次数/24小时，男性为19.3次，女性为21.9次（与对照者相比P=无显著性差异）。此外，通过Cluster分析，我们未能在手术治疗患者与其对照者之间发现脉冲特征的任何差异。目前的数据表明，肢端肥大症的基本异常在于垂体而非下丘脑。
