Abstract：
BACKGROUND: Acromegaly is associated with skeletal fragility and increased prevalence of vertebral fractures (VF). Two isoforms of GH receptor (GHR) have been described, which differ in the presence or absence of a transcript of exon 3 of the GHR gene. Both isoforms produce a functional receptor, but the exon 3-deleted isoforms (d3-GHR) have greater sensitivity to endogenous and recombinant GH than the full-length isoform (fl-GHR).
OBJECTIVE: We conducted a longitudinal, retrospective, observational, single-center study to investigate the role of GHR polymorphism as a prognostic factor of incidental VF (I-VF) in firstgeneration somatostatin analogs (fg-SSAs)-resistant acromegalic patients and treated with Pegvisomant or Pasireotide LAR.
METHODS: Seventy-two patients with active acromegaly were included: 28 patients carried the d3-GHR isoform, and 44 patients carried the fl-GHR isoform. Forty-six patients were treated with Pegvisomant in combination with fg-SSAs, and 26 were treated with Pasireotide LAR. At the last follow-up, 58 patients achieved biochemical control of acromegaly. Eighteen patients carried prevalent VF (P-VFs), while 14 patients experienced the occurrence of I-VFs.
RESULTS: From the group treated with Pegvisomant in combination with fg-SSAs, 32 patients carried the fl-GHR isoform, and 14 carried the d3-GHR isoform. From the group treated with Pasireotide LAR, 12 patients had the fl-GHR isoform, and 14 patients carried the d3-GHR isoform. I-VF occurred more frequently in patients with the fl-GHR isoform compared to d3-GHR (p =0.04); otherwise, I-VF occurred more frequently in patients with the d3-GHR isoform than fl-GHR (p =0.01).
CONCLUSIONS: The GHR polymorphisms could improve the therapeutic approach in acromegaly, tailored to the individual patient, in the context of personalized medicine.
OBJECTIVE: We conducted a longitudinal, retrospective, observational, single-center study to investigate the role of GHR polymorphism as a prognostic factor of incidental VF (I-VF) in firstgeneration somatostatin analogs (fg-SSAs)-resistant acromegalic patients and treated with Pegvisomant or Pasireotide LAR.
METHODS: Seventy-two patients with active acromegaly were included: 28 patients carried the d3-GHR isoform, and 44 patients carried the fl-GHR isoform. Forty-six patients were treated with Pegvisomant in combination with fg-SSAs, and 26 were treated with Pasireotide LAR. At the last follow-up, 58 patients achieved biochemical control of acromegaly. Eighteen patients carried prevalent VF (P-VFs), while 14 patients experienced the occurrence of I-VFs.
RESULTS: From the group treated with Pegvisomant in combination with fg-SSAs, 32 patients carried the fl-GHR isoform, and 14 carried the d3-GHR isoform. From the group treated with Pasireotide LAR, 12 patients had the fl-GHR isoform, and 14 patients carried the d3-GHR isoform. I-VF occurred more frequently in patients with the fl-GHR isoform compared to d3-GHR (p =0.04); otherwise, I-VF occurred more frequently in patients with the d3-GHR isoform than fl-GHR (p =0.01).
CONCLUSIONS: The GHR polymorphisms could improve the therapeutic approach in acromegaly, tailored to the individual patient, in the context of personalized medicine.
摘要：
背景：肢端肥大症与骨骼脆性和椎骨骨折（VF）患病率增加有关。已经描述了GH受体（GHR）的两种同工型，其不同之处在于存在或不存在GHR基因外显子3的转录物。两种同工型都能产生功能性受体,但是外显子3缺失的同种型（d3-GHR）对内源性和重组GH的敏感性高于全长同种型（fl-GHR）。
目的：我们进行了纵向，回顾性,观察,单中心研究在第一代生长抑素类似物（fg-SSAs）耐药肢端肥大症患者中，GHR多态性作为附带VF（I-VF）预后因素的作用，并接受Pegvisomant或PasireotideLAR治疗。
方法：纳入72例活动性肢端肥大症患者：28例患者携带d3-GHR亚型，44例患者携带fl-GHR亚型。46例患者接受了Pegvisomant联合fg-SSAs治疗，26例接受帕西瑞奥肽LAR治疗。在最后一次随访中，58例患者实现肢端肥大症的生化控制。18例患者携带普遍的VF（P-VFs），而14例患者经历了I-VFs的发生。
结果：在使用Pegvisomant联合fg-SSAs治疗的组中，32例患者携带fl-GHR亚型，和14携带d3-GHR同种型。从PasireotideLAR治疗的组中，12例患者具有fl-GHR亚型，14例患者携带d3-GHR亚型。与d3-GHR相比，fl-GHR同种型患者的I-VF发生频率更高（p=0.04）；否则，与fl-GHR同种型患者相比，d3-GHR同种型患者的I-VF发生频率更高（p=0.01）。
结论：GHR多态性可以改善肢端肥大症的治疗方法，为个体患者量身定做，在个性化医疗的背景下。
目的：我们进行了纵向，回顾性,观察,单中心研究在第一代生长抑素类似物（fg-SSAs）耐药肢端肥大症患者中，GHR多态性作为附带VF（I-VF）预后因素的作用，并接受Pegvisomant或PasireotideLAR治疗。
方法：纳入72例活动性肢端肥大症患者：28例患者携带d3-GHR亚型，44例患者携带fl-GHR亚型。46例患者接受了Pegvisomant联合fg-SSAs治疗，26例接受帕西瑞奥肽LAR治疗。在最后一次随访中，58例患者实现肢端肥大症的生化控制。18例患者携带普遍的VF（P-VFs），而14例患者经历了I-VFs的发生。
结果：在使用Pegvisomant联合fg-SSAs治疗的组中，32例患者携带fl-GHR亚型，和14携带d3-GHR同种型。从PasireotideLAR治疗的组中，12例患者具有fl-GHR亚型，14例患者携带d3-GHR亚型。与d3-GHR相比，fl-GHR同种型患者的I-VF发生频率更高（p=0.04）；否则，与fl-GHR同种型患者相比，d3-GHR同种型患者的I-VF发生频率更高（p=0.01）。
结论：GHR多态性可以改善肢端肥大症的治疗方法，为个体患者量身定做，在个性化医疗的背景下。
