GROWTH HORMONE RELEASING HORMONE ANTAGONIST INFUSION IN ACROMEGALICS

肢端肥大症是一种由生长激素（GH）过度产生引起的疾病。 大多数病例是由于垂体瘤。关于这些肿瘤形成的原因有两种理论：（1）细胞染色体的突变导致肿瘤转化并随后形成肿瘤。(2)生长激素释放激素（GHRH）（一种由下丘脑产生的刺激生长激素分泌细胞生长和功能的因子）的过度释放刺激生长激素产生细胞繁殖并产生大量的生长激素。 这两个理论的结合也可以是功能性的。 此外，GHRH可以由垂体瘤细胞产生。 我们的假设是GHRH在引起肢端肥大症的垂体瘤的形成中起重要作用，并在维持肢端肥大症的过度GH分泌中起重要作用。 我们将尝试通过给予肢端肥大症患者GHRH拮抗剂（GHRH-Ant）来回答这个问题，GHRH-Ant是一种合成分子，可以阻断GHRH对GH产生细胞的作用。将研究两组患者：（a）15名患者（A组）将在2个不同的场合进行24小时频繁的血浆GH血样采集，目的是显示在没有任何干预的情况下，肢端肥大症中的GH分泌模式不会每天改变，因此我们在GHRH-Ant给药期间观察到的任何变化都是有意义的。 (b)10例最近诊断为肢端肥大症的患者，计划进行垂体手术（B组），将接受静脉（i. v.）输注GHRH-Ant 7天。 将每10分钟测量一次血浆GH，持续24小时，并在GHRH-Ant输注前和输注结束时评估GH对引起肢端肥大症异常GH反应的因素（静脉注射促甲状腺素释放激素（TRH）和口服葡萄糖）和静脉注射GHRH的反应。 将在GHRH-Ant输注前后通过垂体MRI扫描测量GHRH-Ant对垂体肿瘤大小的影响。 在垂体手术时，将获得垂体肿瘤样本，以在实验室中研究GHRH-Ant对肿瘤细胞产生GH的影响。 如果GHRH-Ant抑制GH的分泌并减小垂体瘤的大小，我们将得出结论，GHRH在导致肢端肥大症的垂体瘤的形成中起作用，并在维持这种疾病的异常GH分泌中起作用。

Acromegaly is a disease caused by excessive growth hormone (GH) production. The majority of cases are due to pituitary gland tumors. There are two theories about the cause of these tumors formation: (1) A mutation in a chromosome of a cell leads to neoplastic transformation and subsequent formation of a tumor. (2) Excessive release of GH-releasing hormone (GHRH) (a factor produced by the hypothalamus that stimulates the growth and function of GH-secreting cells) stimulates GH-producing cells to multiply and produce large amounts of GH. Combinations of these two theories could be also functional. Moreover, GHRH can be produced by the pituitary tumor cells. Our hypothesis is that GHRH plays an important role in the formation of the pituitary tumors that cause acromegaly, and in maintaining the excessive GH secretion in acromegaly. We will attempt to answer this question by administering GHRH-antagonist (GHRH-Ant), a synthetic molecule that blocks the action of GHRH on the GH-producing cells, to patients with acromegaly. Two groups of patients will be studied: (a) Fifteen patients (group A) will have frequent blood sampling for plasma GH for 24 hours on 2 different occasions with the goal to show that without any intervention the GH secretion pattern in acromegaly does not change from day to day so that any changes that we could observe during administration of GHRH-Ant would be meaningful. (b) Ten patients recently diagnosed with acromegaly, who are scheduled to have pituitary surgery (group B) will receive intravenous (i.v.) infusion of GHRH-Ant for 7 days. Plasma GH will be measured every 10 min for 24 h, and the GH responses to factors that cause abnormal GH responses in acromegaly (i.v. thyrotropin-releasing hormone (TRH) and oral glucose) and to i.v. GHRH will be assessed before and at the end of the GHRH-Ant infusion. The effect of GHRH-Ant on the pituitary tumor size will be measured by pituitary MRI scans before and after the GHRH-Ant infusion. At the time of pituitary surgery, a pituitary tumor sample will be obtained to study the effects of GHRH-Ant on the GH production by the tumor cells in the laboratory. If the GHRH-Ant suppresses the secretion of GH and decreases the size of the pituitary tumors, we will conclude that GHRH plays a role in the formation of the pituitary tumors that cause acromegaly and in maintaining abnormal GH secretion in this disease.