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肢端肥大症的当前治疗方法。

Current management of acromegaly.

作者信息

Díez J J, Iglesias P

机构信息

Department of Endocrinology, Hospital La Paz, Madrid, Spain.

出版信息

Expert Opin Pharmacother. 2000 Jul;1(5):991-1006. doi: 10.1517/14656566.1.5.991.

Abstract

Acromegaly, a chronic disease of growth hormone (GH) hypersecretion, is most typically caused by a pituitary adenoma. Early diagnosis is critical for prompt intervention to prevent deleterious effects of prolonged exposure to elevated GH and insulin-like growth factor Type I (IGF-I) levels. Current therapy for acromegaly includes several options: surgery, radiotherapy and pharmacotherapy. Transsphenoidal adenomectomy remains a mainstay of therapy for acromegaly. Cure rates are high in microadenomas, but < 50% in macroadenomas. Conventional and stereotactic procedures for radiation therapy are also effective in decreasing GH levels in acromegalic patients, but they need years to normalise GH hypersecretion and carry with them the risk of hypopituitarism. The major classes of drugs currently used to treat acromegaly are dopamine agonists and analogues of somatostatin. Dopamine agonists bind to the D2 receptor and suppress GH hypersecretion in some patients with acromegaly. Their clinical effectiveness is modest, although promising results have been obtained with two novel compounds, quinagolide and cabergoline, that possess long duration of action. Somatostatin analogues have been shown to improve clinical symptoms of acromegaly, decrease hypersecretion of GH and IGF-I and reduce tumour volume in a clinically significant number of patients. Octreotide is administered by s.c. route several times a day, but the recently developed sustained release formulations (octreotide LAR and SR lanreotide) are administered only every 7-28 days by i.m. injections. The complications associated with somatostatin analogues are small, relative to the benefits. Lastly, compounds with a novel mechanism of action, the GH receptor antagonists, are presently under investigation.

摘要

肢端肥大症是一种生长激素(GH)分泌过多的慢性疾病,最常见的病因是垂体腺瘤。早期诊断对于及时干预至关重要,可预防长期暴露于升高的GH和胰岛素样生长因子I(IGF-I)水平所带来的有害影响。目前肢端肥大症的治疗方法有多种选择:手术、放疗和药物治疗。经蝶窦腺瘤切除术仍然是肢端肥大症治疗的主要手段。微腺瘤的治愈率很高,但大腺瘤的治愈率小于50%。传统放疗和立体定向放疗在降低肢端肥大症患者的GH水平方面也有效,但需要数年时间才能使GH分泌过多恢复正常,且存在垂体功能减退的风险。目前用于治疗肢端肥大症的主要药物类别是多巴胺激动剂和生长抑素类似物。多巴胺激动剂与D2受体结合,可抑制一些肢端肥大症患者的GH分泌过多。它们的临床疗效一般,不过两种具有长效作用的新型化合物喹高利特和卡麦角林已取得了有前景的结果。生长抑素类似物已被证明可改善肢端肥大症的临床症状,减少GH和IGF-I的分泌过多,并使相当数量的患者肿瘤体积缩小。奥曲肽通过皮下途径每日给药数次,但最近开发的缓释制剂(长效奥曲肽和缓释兰瑞肽)仅通过肌肉注射每7 - 28天给药一次。与生长抑素类似物相关的并发症相对于其益处来说较少。最后,具有新作用机制的化合物——GH受体拮抗剂目前正在研究中。

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