Primary medical therapy for acromegaly: An open, prospective, multicenter study of the effects of subcutaneous and intramuscular slow-release octreotide on growth hormone, insulin-like growth factor-I, and tumor size
Primary medical therapy for acromegaly: An open, prospective, multicenter study of the effects of subcutaneous and intramuscular slow-release octreotide on growth hormone, insulin-like growth factor-I, and tumor size
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DOI：
10.1210/jc.2001-012012
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发表时间：
2002-10-01
影响因子：
5.8
通讯作者：
Wardlaw, JM
中科院分区：
文献类型：
--
作者：
Bevan, JS;Atkin, SL;Wardlaw, JM
肢端肥大症的常规手术和放射治疗都有局限性。关于使用生长抑素类似物奥曲肽(OCT)作为主要药物治疗的数据很少。在英国的9个内分泌中心对27名新诊断的肢端肥大症患者进行了一项开放的前瞻性研究。大腺瘤20例，微腺瘤7例。治疗前24周(第1期)，13例血清生长激素(GH)>5MU/L(2MU/L)的患者接受OCT治疗，起始剂量为100µg，每日3次，4周后增至200µg/d。分别于0周、4周、12周和24周进行五点生长激素测定，并在0周、12周和24周采用标准方案进行高分辨率垂体成像(25例患者行磁共振成像，2例患者行计算机断层扫描)。肿瘤的大小和体积由中央报告的神经放射科医生计算，结果由另一位独立的神经放射科医生审计。24周后，15名患者进入研究的第二阶段，直接转向每月注射OCT仓库配方，Sandostatin长效释放(OCT-LAR)。治疗前血清GH浓度中位数为30.7mU/L(范围6.7~141.4)。术后血清GH降至<5mU/L者9例(38%)，IGF-I降至正常者8例(33%)。所有27个肿瘤在SCOCT期间全部缩小；微腺瘤的肿瘤体积缩小的中位数为49%(范围12-73)，大腺瘤的肿瘤体积缩小的中位数为43%(范围6-92)。OCT-LAR治疗24周后(2期结束)，14例患者中有11例(79%)生长激素水平低于5mU/升，15例患者中有8例(53%)IGF-I正常。在接受OCT-LAR(10个大腺瘤)的15名患者中，48周扫描显示总体肿瘤体积进一步缩小24%。研究结束时，79%的患者平均血清生长激素水平低于5mU/升，53%的患者IGF-I水平正常，73%的患者肿瘤缩小超过30%。29%的患者达到了所有3个目标，但在研究的任何阶段，治疗前GH水平超过50mU/升的患者都没有达到这一目标。OCT的初级药物治疗为肢端肥大症患者提供了GH/IGF-I水平正常化和肿瘤显著缩小的前景。这最有可能发生在治疗前生长激素水平低于50微升(20微克/升)的患者。
Conventional surgery and radiotherapy for acromegaly have limitations. There are few data on the use of the somatostatin analog octreotide (Oct) as primary medical therapy. An open prospective study of 27 patients with newly diagnosed acromegaly was conducted in nine endocrine centers in the United Kingdom. Twenty patients had macroadenomas, and 7 had microadenomas. For the first 24 wk (phase 1), patients received sc Oct in an initial dose of 100 mug, 3 times daily, increased to 200 mug three times daily after 4 wk in the 13 patients whose mean serum GH remained greater than 5 mU/liter (2 mug/liter). Five-point GH profiles were performed at 0, 4,12, and 24 wk, and high resolution pituitary imaging using a standard protocol was performed at 0, 12, and 24 wk (magnetic resonance imaging in 25 patients and computed tomography in 2). Tumor dimensions and volumes were calculated by a central, reporting neuroradiologist, and the results were audited by a second, independent neuroradiologist. After 24 wk, 15 patients proceeded to phase 2 of the study with a direct switch to monthly injections of the depot formulation of Oct, Sandostatin long-acting release (Oct-LAR). Further GH profiles were performed at 36 and 48 wk, and pituitary imaging was performed at 48 wk.The median pretreatment serum GH concentration was 30.7 mU/liter (range, 6.7-141.4). During se Oct, serum GH fell to less than 5 mU/liter in 9 patients (38%), and IGF-I fell to normal in 8 patients (33%). All 27 tumors shrank during sc Oct; for microadenomas the median tumor volume reduction was 49% (range, 12-73), and for macroadenomas it was 43% (range, 6-92). After 24 wk of Oct-LAR (end of phase 2), the GH level was less than 5 mU/Iiter in 11 of 14 patients (79%), and IGF-I was normal in 8 of 15 patients (53%). In the 15 patients given Oct-LAR (10 macroadenomas), wk 48 scans showed a further overall median tumor volume reduction of 24%. At the end of the study 79% of patients had mean serum GH levels below 5 mU/liter, 53% had normal IGF-I levels, and 73% showed greater than 30% tumor shrinkage. Twenty-nine percent of patients achieved all 3 targets, but no patient with pretreatment GH levels above 50 mU/Iiter did so at any stage of the study.Primary medical therapy with Oct offers the prospect of normalization of GH/IGF-I levels together with substantial tumor shrinkage in a significant subset of acromegalic patients. This is most likely to occur in patients with pretreatment GH levels less than 50 mU/Iiter (20 mug/liter).