Hunter S J, Shaw J A, Lee K O, Wood P J, Atkinson A B, Bevan J S
Metabolic Unit, Royal Victoria Hospital, Belfast, UK.
Clin Endocrinol (Oxf). 1999 Feb;50(2):245-51. doi: 10.1046/j.1365-2265.1999.00668.x.
To compare the effects of monthly intra-muscular injections of a long acting preparation of octreotide, Sandostatin LAR, with multiple daily subcutaneous injections of octreotide and to study the interrelationships between mean 24 h growth hormone profile, serum total and free IGF-1 levels, 24 h urinary growth hormone levels and serum IGFBP-3.
Patients were assessed by 24 h GH profile off octreotide or any other GH modifying drug therapy; on subcutaneous octreotide (200-600 micrograms daily in divided doses for six weeks); and 28 days after the second of two injections of Sandostatin LAR (20 mg by intra-muscular injection) administered 28 days apart. Serum total and free IGF-1, serum IGFBP-3 and 24 h urinary GH were also measured on each occasion.
Sandostatin LAR was well tolerated. None of the patients reported any adverse effect and all completed the study uneventfully. Mean GH off treatment was 10.1 +/- 3.0 micrograms/l falling equally significantly (P < 0.05) during therapy with subcutaneous octreotide to 3.0 +/- 0.7 micrograms/l and Sandostatin LAR to 2.8 +/- 0.7 micrograms/l. Fasting 0900 h GH was significantly reduced (P < 0.05) on Sandostatin LAR (3.0 +/- 0.7 micrograms/l) compared with subcutaneous octreotide (5.1 +/- 1.2 micrograms/l). Mean total IGF-1 off treatment was 658.6 +/- 56.1 micrograms/l and was reduced to a comparable extent with subcutaneous octreotide and Sandostatin LAR (466.0 +/- 59.7 and 448.6 +/- 59.5 micrograms/l respectively; both P < 0.05). Free IGF-1 off treatment was 3.1 +/- 0.6 micrograms/l and was reduced equally by subcutaneous octreotide and Sandostatin LAR (1.2 +/- 0.2 and 1.2 +/- 0.2 micrograms/l; both P < 0.05). IGFBP-3 was reduced to a greater extent during Sandostatin LAR than during subcutaneous octreotide (4518.2 +/- 247.3 vs 5132.8 +/- 280.7 micrograms/l; P < 0.05). Twenty-four hour urinary GH excretion was reduced to a comparable extent with both therapies. Highly significant positive correlations were found between mean 24 h GH levels and free IGF-1 (r = 0.66, P < 0.0001) and 24 h urinary GH excretion (r = 0.94, P < 0.0001). The relationships between mean 24 h GH levels and total IGF-1 and IGFBP-3 although significant showed less powerful correlations.
These results suggest that Sandostatin LAR is well tolerated and as effective as subcutaneous octreotide. In addition, urinary growth hormone and serum free IGF-1 may prove valuable for outpatient follow-up of acromegalic patients, as both correlate well with mean 24 h serum growth hormone levels.
比较每月肌肉注射长效奥曲肽制剂善龙（Sandostatin LAR）与每日多次皮下注射奥曲肽的效果，并研究24小时平均生长激素水平、血清总胰岛素样生长因子-1（IGF-1）和游离IGF-1水平、24小时尿生长激素水平与血清IGF结合蛋白-3（IGFBP-3）之间的相互关系。
对患者进行评估，分别为停用奥曲肽或任何其他生长激素调节药物治疗时的24小时生长激素水平；皮下注射奥曲肽时（每日200 - 600微克，分剂量给药，共六周）；以及在间隔28天注射两次善龙（每次肌肉注射20毫克）后的第28天。每次均测量血清总IGF-1和游离IGF-1、血清IGFBP-3以及24小时尿生长激素。
善龙耐受性良好。所有患者均未报告任何不良反应，均顺利完成研究。治疗前平均生长激素水平为10.1±3.0微克/升，皮下注射奥曲肽治疗期间显著下降至3.0±0.7微克/升（P<0.05），善龙治疗后降至2.8±0.7微克/升（P<0.05）。与皮下注射奥曲肽（5.1±1.2微克/升）相比，善龙治疗时09:00空腹生长激素水平显著降低（P<0.05）（3.0±0.7微克/升）。治疗前平均总IGF-1为658.6±56.1微克/升，皮下注射奥曲肽和善龙治疗后均降至相当程度（分别为466.0±59.7微克/升和448.6±59.5微克/升；均P<0.05）。治疗前游离IGF-1为3.1±0.6微克/升，皮下注射奥曲肽和善龙治疗后均同等程度降低（分别为1.2±0.2微克/升和1.2±0.2微克/升；均P<0.05）。善龙治疗期间IGFBP-3的降低程度大于皮下注射奥曲肽（4518.2±247.3微克/升对5132.8±280.7微克/升；P<0.05）。两种治疗方法使24小时尿生长激素排泄降低程度相当。24小时平均生长激素水平与游离IGF-1（r = 0.66，P<0.0001）和24小时尿生长激素排泄（r = 0.94，P<0.0001）之间存在高度显著的正相关。24小时平均生长激素水平与总IGF-1和IGFBP-3之间的关系虽然显著，但相关性较弱。
这些结果表明善龙耐受性良好，与皮下注射奥曲肽效果相同。此外，尿生长激素和血清游离IGF-1可能对肢端肥大症患者的门诊随访有价值，因为两者均与24小时血清生长激素平均水平密切相关。
