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肢端肥大症患者中生长抑素类似物SMS 201-995持续皮下泵输注与皮下注射方案的比较

Continuous subcutaneous pump infusion of somatostatin analogue SMS 201-995 versus subcutaneous injection schedule in acromegalic patients.

作者信息

Christensen S E, Weeke J, Orskov H, Møller N, Flyvbjerg A, Harris A G, Lund E, Jørgensen J

机构信息

Second University Clinic of Internal Medicine, Kommunehospitalet, Aarhus, Denmark.

出版信息

Clin Endocrinol (Oxf). 1987 Sep;27(3):297-306. doi: 10.1111/j.1365-2265.1987.tb01156.x.

Abstract

Diurnal serum GH patterns were determined in 10 acromegalic patients before treatment, after 3 d continuous s.c. pump infusion and then after 3 d with three equal daily s.c. injections in both instances totalling 100 micrograms/24 h. Subcutaneous injections (33 micrograms) induced impressive suppression of serum GH lasting 3-6 h in eight patients followed by escape to pretreatment values before the next injection. In contrast, continuous infusion resulted in greater and more stable 24 h suppression to the levels reached at the nadir between injections. Suppression of mean 24 h serum GH below 5 ng/ml was achieved by pump treatment in four patients, while two patients had mean values between 5 ng/ml and 10 ng/ml. In four patients occasional or all levels were above 10 ng/ml (24 h average 12.4-102 ng/ml) implying either that adequate suppression by the SMS 201-995, was impossible during the 3 d pump infusion period, or that the dose administered was inadequate. Carbohydrate tolerance was unaffected in either regimen, indicating that reduction in insulin antagonistic hormones balanced inhibition of insulin release. Interestingly, and in contrast to somatostatin, SMS 201-995 did not inhibit TSH release. No untoward effects were observed at the moderate dosage and blood clinical chemistry was unchanged. Fairly constant diurnal serum SMS 201-995 values were obtained during pump infusion, while levels undulated inversely with serum GH during injection treatment. Average diurnal serum somatostatin-C immunoreactivity (all patients) decreased from 496 +/- 129 (mean +/- SD) to 385 +/- 100 ng/ml (P less than 0.003) during pump treatment and did not decrease further during the following 3 d injection treatment (363 +/- 76 ng/ml). The normal adult mean is 179 +/- 40 ng/ml. Computer tomographic (CT) scans of the sellar region were performed in all patients before and after the experimental week. Two patients had extracellular tumours whose size decreased from 8.2 to 4.1 cm3 and from 12.6 to 10.5 cm3. The results demonstrate that superior and stable suppression of GH secretion is obtained during continuous s.c. pump infusion of SMS 201-995.

摘要

在10例肢端肥大症患者治疗前、连续皮下泵输注3天以及随后每日皮下注射3次(两种情况下总量均为100微克/24小时)共3天后,测定了其日间血清生长激素(GH)水平。皮下注射(33微克)使8例患者的血清GH受到显著抑制,持续3 - 6小时,随后在下一次注射前回升至治疗前水平。相比之下,连续输注导致24小时内对两次注射之间最低点所达到水平的抑制作用更强且更稳定。通过泵治疗,4例患者24小时平均血清GH抑制至5纳克/毫升以下,而2例患者的平均值在5纳克/毫升至10纳克/毫升之间。4例患者偶尔或所有水平均高于10纳克/毫升(24小时平均值为12.4 - 102纳克/毫升),这意味着在3天泵输注期间,要么无法通过SMS 201 - 995实现充分抑制,要么给药剂量不足。两种给药方案对碳水化合物耐受性均无影响,表明胰岛素拮抗激素的减少与胰岛素释放的抑制相平衡。有趣的是,与生长抑素不同,SMS 201 - 995不抑制促甲状腺激素(TSH)释放。在中等剂量下未观察到不良反应,血液临床化学指标未改变。在泵输注期间获得了相当稳定的日间血清SMS 201 - 995值,而在注射治疗期间,其水平与血清GH呈反向波动。在泵治疗期间,所有患者的平均日间血清生长抑素 - C免疫反应性从496±129(平均值±标准差)降至385±100纳克/毫升(P<0.003),在随后3天的注射治疗期间(363±76纳克/毫升)未进一步下降。正常成年人平均值为179±40纳克/毫升。在实验周前后,对所有患者进行了蝶鞍区计算机断层扫描(CT)。2例患者有细胞外肿瘤,其大小从8.2立方厘米降至4.1立方厘米,从12.6立方厘米降至10.5立方厘米。结果表明,在连续皮下泵输注SMS 201 - 995期间,可获得对GH分泌的更优且稳定的抑制。

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