长效奥曲肽（善龙）治疗的肢端肥大症患者的生长激素结合蛋白与生长激素可利用性

Growth hormone binding protein and growth hormone availability in acromegalic patients treated with long-acting octreotide (Sandostatin-LAR).

作者信息

Fisker S, Kaal A, Montini M, Pedroncelli A, Pagani G, Orskov H

机构信息

Medical Department M (Endocrinology and Diabetes), University Hospital, Aarhus, Denmark.

出版信息

Eur J Endocrinol. 1997 Jan;136(1):61-6. doi: 10.1530/eje.0.1360061.

DOI:10.1530/eje.0.1360061

PMID:9037128

Abstract

OBJECTIVE

In the medical treatment of acromegaly different factors are influential; among these the impact on growth hormone binding protein (GHBP) has not been clarified.

DESIGN

Twenty acromegalic patients and nineteen age- and gender-matched normal subjects participated in this study. The patients were treated for 21 months with depot long-acting microsphere-enclosed octreotide (Sandostatin-LAR). Previously, all the patients were treated s.c. with octreotide t.i.d. After a 2-week wash-out period (baseline) the patients received the first i.m. injection of the long-acting octreotide. The first two injections were administered at 60-day intervals; thereafter the injections were at 28-day intervals.

METHODS

The levels of GHBP, complexed GHBP, growth hormone (GH) and insulin-like growth factor-I (IGF-I) were determined in fasting serum samples.

RESULTS

In the 2-week wash-out period GHBP levels decreased from 1.13 +/- 0.17 to 0.92 +/- 0.15 nmol/l (P < 0.05). During the 21-months treatment, GHBP increased again to 1.10 +/- 0.16 nmol/l. In the age- and gender-matched control group GHBP levels were significantly higher at all times (1.95 +/- 0.21 nmol/l. P(all) < 0.02). Mean levels of 8-h GH decreased from 12.6 +/- 2.58 microg/l at baseline to 1.97 +/- 0.20 microg/l after 21 months of treatment (P < 0.05). Mean 8-h GH levels were unchanged during long-acting octreotide treatment compared with levels during s.c. treatment (1.97 +/- 0.20 microg/l and 1.90 +/- 0.20 microg/l respectively). In fasting blood samples GH-complexed GHBP ranged from 13.8 +/- 2.4% (9 months) to 25.4 +/- 4.5% (baseline) of total GHBP. Serum IGF-I increased from 367 +/- 45 to 764 +/- 80 microg/l (P < 0.05) during the 2-week wash-out period and decreased to 290 +/- 35 microg/l (P < 0.05) after 21 months of treatment with long-acting octreotide. IGF-I levels after 21 months were significantly lower than during s.c. octreotide treatment (P < 0.05).

CONCLUSION

Serum GHBP levels are similar during treatment with long-acting octreotide as compared with regular octreotide. Furthermore, significant changes in GHBP can occur within 2 weeks. Finally, in addition to the lowering effect on GH levels, the induced increase in GHBP levels may imply a further advantage in octreotide treatment of acromegaly. circulating GH bound to GHBP may less readily reach the tissues.

摘要

目的

在肢端肥大症的医学治疗中，多种因素具有影响作用；其中，对生长激素结合蛋白（GHBP）的影响尚未明确。

设计

20例肢端肥大症患者和19例年龄及性别匹配的正常受试者参与了本研究。患者接受长效微球包裹的奥曲肽（善龙）治疗21个月。在此之前，所有患者均接受皮下注射奥曲肽，每日3次。经过2周的洗脱期（基线期）后，患者接受首次肌肉注射长效奥曲肽。前两次注射间隔60天；此后注射间隔为28天。

方法

在空腹血清样本中测定GHBP、复合GHBP、生长激素（GH）和胰岛素样生长因子-I（IGF-I）的水平。

结果

在2周的洗脱期内，GHBP水平从1.13±0.17降至0.92±0.15 nmol/l（P<0.05）。在21个月的治疗期间，GHBP再次升高至1.10±0.16 nmol/l。在年龄及性别匹配的对照组中，GHBP水平在所有时间均显著更高（1.95±0.21 nmol/l，P（所有）<0.02）。8小时GH的平均水平从基线时的12.6±2.58μg/l降至治疗21个月后的1.97±0.20μg/l（P<0.05）。与皮下注射治疗期间的水平相比，长效奥曲肽治疗期间8小时GH的平均水平无变化（分别为1.97±0.20μg/l和1.90±0.20μg/l）。在空腹血样本中，与GH结合的GHBP占总GHBP的比例在9个月时为13.8±2.4%，在基线时为25.4±4.5%。血清IGF-I在2周的洗脱期内从367±45升高至764±80μg/l（P<0.05），在用长效奥曲肽治疗21个月后降至290±35μg/l（P<0.05）。21个月后的IGF-I水平显著低于皮下注射奥曲肽治疗期间（P<0.05）。