Clinical Characteristics and Therapeutic Responses in Patients with Germ-Line AIP Mutations and Pituitary Adenomas: An International Collaborative Study
Clinical Characteristics and Therapeutic Responses in Patients with Germ-Line AIP Mutations and Pituitary Adenomas: An International Collaborative Study
复制标题
DOI：
10.1210/jc.2009-2556
复制
发表时间：
2010-11-01
影响因子：
5.8
通讯作者：
Beckers, Albert
中科院分区：
文献类型：
--
作者：
Daly, Adrian F.;Tichomirowa, Maria A.;Beckers, Albert
背景：AIP突变(AIPmut)可导致垂体腺瘤的易感性，这种易感性发生在家族性孤立性垂体腺瘤中，在散发性病例中较少发生。AIPmut相关垂体腺瘤的临床和治疗特征尚未得到全面研究。目的：本研究的目的是评估AIPmut垂体腺瘤的临床和治疗特点。设计：本研究是一项国际性、多中心、回顾性病例收集/数据库分析。地点：本研究在36个三级转诊内分泌和临床遗传科进行。患者包括96例AIPmut和垂体腺瘤患者和232例匹配的AIPmut阴性肢端肥大症患者。结果：AIPmut患者主要为年轻和男性(63.5%)；50%的患者首发症状为儿童/青少年。诊断时，肿瘤多为大腺瘤(93.3%)；常见的是侵犯和侵犯。促生长激素瘤占队列的78.1%；还有催乳素瘤(n=13)、非分泌性腺瘤(n=7)和1例分泌性TSH腺瘤。AIPmut生长激素瘤体积较大(P=0.00026)，GH水平较高(P=0.00068)，生长延长率(P=0.018)和催乳素分泌(P=0.00023)较正常对照组提前20年(P<；0.000001)。巨人症在AIPmut组中更为常见(P<；0.000001)。与对照组相比，AIPmut生长激素瘤患者接受了更多的手术治疗(P=0.00069)，生长激素(P=0.00037)和胰岛素样生长因子-I(P=0.028)的下降较少，肿瘤缩小较小(P<；0.00001)。AIPmut催乳素瘤多见于年轻男性，常需手术或放射治疗。年轻患者易患侵袭性疾病，通常是在家族背景下，这表明AIPmut垂体瘤的早期诊断可能具有临床实用价值。(J临床内分泌Metab 95：E373-E383,2010)
Context: AIP mutations (AIPmut) give rise to a pituitary adenoma predisposition that occurs in familial isolated pituitary adenomas and less often in sporadic cases. The clinical and therapeutic features of AIPmut-associated pituitary adenomas have not been studied comprehensively.Objective: The objective of the study was to assess clinical/therapeutic characteristics of AIPmut pituitary adenomas.Design: This study was an international, multicenter, retrospective case collection/database analysis.Setting: The study was conducted at 36 tertiary referral endocrine and clinical genetics departments.Patients: Patients included 96 patients with germline AIPmut and pituitary adenomas and 232 matched AIPmut-negative acromegaly controls.Results: The AIPmut population was predominantly young and male (63.5%); first symptoms occurred as children/adolescents in 50%. At diagnosis, most tumors were macroadenomas (93.3%); extension and invasion was common. Somatotropinomas comprised 78.1% of the cohort; there were also prolactinomas (n = 13), nonsecreting adenomas (n = 7), and a TSH-secreting adenoma. AIPmut somatotropinomas were larger (P = 0.00026), with higher GH levels (P = 0.00068), more frequent extension (P = 0.018) and prolactin cosecretion (P = 0.00023), and occurred 2 decades before controls (P < 0.000001). Gigantism was more common in the AIPmut group (P < 0.000001). AIPmut somatotropinoma patients underwent more surgical interventions (P = 0.00069) and had lower decreases in GH (P = 0.00037) and IGF-I (P = 0.028) and less tumor shrinkage with somatostatin analogs (P < 0.00001) vs. controls. AIPmut prolactinomas occurred generally in young males and frequently required surgery or radiotherapy.Conclusions: AIPmut pituitary adenomas have clinical features that may negatively impact treatment efficacy. Predisposition for aggressive disease in young patients, often in a familial setting, suggests that earlier diagnosis of AIPmut pituitary adenomas may have clinical utility. (J Clin Endocrinol Metab 95: E373-E383, 2010)