Jenkins P J, Emery M, Howling S J, Evanson J, Besser G M, Monson J P
Department of Endocrinology, St. Bartholomew's Hospital, London, UK.
Horm Res. 2004;62(5):227-32. doi: 10.1159/000081418. Epub 2004 Oct 11.
BACKGROUND/AIMS: The efficacy of transsphenoidal surgery in the treatment of patients with acromegaly is largely dependent on tumour size. A reduction in pituitary tumour volume by medical therapy might therefore improve subsequent surgical cure rates. This study prospectively determined the effects of the depot somatostatin analogue octreotide LAR on pituitary tumour size, GH and IGF-I levels and clinical symptoms in a cohort of previously untreated patients with acromegaly.
Six patients newly diagnosed with acromegaly (mean age 53 years; range 42-76 years) received intramuscular octreotide LAR every 28 days for 6 months. The initial dose of LAR was 20 mg, but increased to 30 mg after the initial 3 injections if mean GH levels were >5 mU/l. Prior to commencing LAR therapy, each patient received 3 injections of subcutaneous octreotide (50, 100 and 200 mug) in a randomized order on separate days, and the serum GH response was measured. Pituitary tumour volume was calculated from MRI or computed tomography scans at baseline, then 3 and 6 months after initiation of treatment, and assessed by a 'blinded' radiologist in random order. At baseline, 4 patients had a macroadenoma and 2 patients had a microadenoma. For the latter, the whole gland volume was measured.
Serum GH levels decreased from 29.6 +/- 19.2 mU/l (mean +/- SD) at baseline to 12.1 +/- 10.5 mU/l at 3 months and 10.4 +/- 9.3 mU/l at 6 months. Three patients achieved a mean serum GH level of <5 mU/l. In these patients, the serum GH had declined to <5 mU/l in response to a single 100 mug subcutaneous octreotide injection. Serum IGF-I levels decreased by a mean of 45 +/- 7.4%. Tumour volume decreased in all patients: mean baseline volume 2,175 mm(3) (range 660-6,998) decreasing to 1,567 mm(3) (range 360-4,522) at 3 months (p < 0.05) and 1,293 mm(3) (range 280-4,104) at 6 months (p < 0.002). The mean percentage decrease in size was 29% (range -54 to +4%) at 3 months (p < 0.02) and 47% (range 21-97%) at 6 months (p < 0.002). There was no statistically significant correlation between GH response and tumour shrinkage.
A single test dose of subcutaneous octreotide may be useful in predicting the subsequent efficacy of octreotide LAR. Octreotide LAR results in significant shrinkage of pituitary tumours of newly diagnosed patients with acromegaly. Whether its administration to such patients for 6-12 months can improve the efficacy of subsequent transsphenoidal surgery will require further study.
背景/目的：经蝶窦手术治疗肢端肥大症患者的疗效在很大程度上取决于肿瘤大小。因此，通过药物治疗减少垂体瘤体积可能会提高后续手术治愈率。本研究前瞻性地确定了长效生长抑素类似物奥曲肽LAR对一组未经治疗的肢端肥大症患者的垂体瘤大小、生长激素（GH）和胰岛素样生长因子-I（IGF-I）水平以及临床症状的影响。
6例新诊断为肢端肥大症的患者（平均年龄53岁；范围42 - 76岁）每28天接受一次肌肉注射奥曲肽LAR，共6个月。LAR的初始剂量为20mg，但如果平均GH水平>5mU/l，则在最初3次注射后增加至30mg。在开始LAR治疗前，每位患者在不同日期以随机顺序接受3次皮下注射奥曲肽（50、100和200μg），并测量血清GH反应。垂体瘤体积通过基线时、治疗开始后3个月和6个月的磁共振成像（MRI）或计算机断层扫描（CT）扫描计算得出，并由一位“盲法”放射科医生按随机顺序进行评估。基线时，4例患者为大腺瘤，2例患者为微腺瘤。对于后者，测量整个腺体体积。
血清GH水平从基线时的29.6±19.2mU/l（平均值±标准差）降至3个月时的12.1±10.5mU/l和6个月时的10.4±9.3mU/l。3例患者的平均血清GH水平<5mU/l。在这些患者中，血清GH在单次皮下注射100μg奥曲肽后降至<5mU/l。血清IGF-I水平平均下降45±7.4%。所有患者的肿瘤体积均减小：基线平均体积2175mm³（范围660 - 6998）在3个月时降至1567mm³（范围360 - 4522）（p<0.05），在6个月时降至1293mm³（范围280 - 4104）（p<0.002）。体积减小的平均百分比在3个月时为29%（范围 - 54至 + 4%）（p<0.02），在6个月时为47%（范围21 - 97%）（p<0.002）。GH反应与肿瘤缩小之间无统计学显著相关性。
单次皮下注射奥曲肽试验剂量可能有助于预测奥曲肽LAR的后续疗效。奥曲肽LAR可使新诊断的肢端肥大症患者的垂体瘤显著缩小。对这些患者给药6 - 12个月是否能提高后续经蝶窦手术的疗效还需要进一步研究。
