Clinical Correlates in Acromegalic Patients with Pituitary Tumours Expressing GSP Oncogenes
Clinical Correlates in Acromegalic Patients with Pituitary Tumours Expressing GSP Oncogenes
复制标题
肢端肥大症患者与表达 GSP 癌基因的垂体瘤的临床相关性
作者：
Michael Buchfelder;Rudolf Fahlbusch;T. Merz;H. Symowski;Eric F. Adams
在此，我们回顾了已发表的肢端肥大症患者的临床特征，这些患者的垂体生长激素瘤表达腺苷酸环化酶激活gsp突变，并对我们自己的176例有或无这些癌基因的患者的数据进行了更新。Gsp癌基因是控制腺苷酸环化酶的GS蛋白的GS-α亚基的密码子201或227中的点突变的结果。它们最终导致细胞内cAMP水平增加，从而导致过度的生长激素（GH）分泌。我们的大系列研究使我们能够鉴定出201号密码子突变的患者和227号密码子缺陷的罕见患者。两组均与无gsp癌基因的患者进行比较。根据以前的研究结果，有没有统计学上的显着差异，属于每个组的患者的年龄，整体平均肿瘤直径，也没有在术前血清GH水平，虽然后者显示出一种趋势是较低的gsp癌基因的患者。口服葡萄糖耐量试验期间不同类型反应的分布（血清GH水平无变化、反常升高或下降超过50%）在3组之间无差异。然而，在227号密码子突变的患者中，表达gsp癌基因的肢端肥大症患者的微腺瘤发生率较高。此外，在密码子227突变的肿瘤中，侵袭性的发生率要低得多（10%对33%）。最后，先前的体外数据表明，表达gsp癌基因的肿瘤可能更有效地响应生长抑素类似物，奥曲肽，已证实了随后的体内研究显示，更好地降低血清GH水平的gsp癌基因的患者。这些发现表明gsp癌基因的存在可能是奥曲肽良好反应的标志。评估手术切除的垂体生长激素瘤的gsp肿瘤状态可能有助于设计最佳的药物治疗方案，以治疗那些需要进一步术后管理的肢端肥大症。
We herein review published findings on the clinical characteristics of acromegalic patients harboring pituitary somatotrophinomas expressing adenylyl cyclase activating gsp mutations and present an update of our own data on a large series of 176 patients with and without these oncogenes. Gsp oncogenes are the result of point mutations in either codon 201 or 227 of the Gs-alpha subunit of the Gs-protein which controls adenylyl cyclase. They result ultimately in increased intracellular cAMP levels and thus in excessive growth hormone (GH) secretion. Our large series has allowed us to characterise patients with mutations in codon 201 and the far rarer group possessing codon 227 defects. Both groups were compared with patients without gsp oncogenes. In accordance with previous findings, there was no statistically significant difference in age of the patients belonging to each group, the overall average tumor diameter nor in pre-operative serum GH levels, although the latter showed a tendency to be lower in patients with gsp oncogenes. The distribution of different types of response during an oral glucose tolerance test (no change, paradoxical rise or greater than 50% decrease in serum GH levels) did not differ between the 3 groups. However, the incidence of microadenomas was higher in acromegalics expressing gsp oncogenes in patients possessing mutations in codon 227. Additionally, the incidence of invasiveness was much lower (10% v. 33%) in those tumors with mutations in codon 227. Finally, previous in-vitro data indicating that gsp oncogene-expressing tumors may respond more efficiently to the somatostatin analogue, octreotide, have been confirmed by subsequent in-vivo studies showing a better reduction in serum GH levels in patients with gsp oncogenes. These latter findings suggest that presence of gsp oncogenes may be a marker for good reponsiveness to octreotide. Assessment of gsp oncoge status of surgically removed pituitary somatotrophinomas may thus be helpful in designing optimal medical therapies in those acromegalics requiring further post-operative management of the disease.
具有和不具有 Gs α 突变的生长激素细胞腺瘤中糖蛋白激素 α 亚基的产生。
DOI：
10.1210/jcem.75.3.1517386
发表时间：
1992
期刊：
The Journal of clinical endocrinology and metabolism
影响因子：
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作者：
Harris,PE;Alexander,JM;Bikkal,HA;Hsu,DW;Hedley-Whyte,ET;Klibanski,A;Jameson,JL
通讯作者：
Jameson,JL