Erem Cihangir, Nuhoglu Irfan, Kocak Mustafa, Yilmaz Mustafa, Sipahi Safiye Tuba, Ucuncu Ozge, Ersoz Halil Onder
Faculty of Medicine, Department of Internal Medicine, Division of Endocrinology and Metabolism, Karadeniz Technical University, Iç Hastaliklari Anabilim Dali, 61080 Trabzon, Turkey.
Endocrine. 2008 Jun;33(3):270-6. doi: 10.1007/s12020-008-9088-4.
Growth hormone/insulin-like growth factor-1(GH/IGF-1) hypersecretion may influence risk factors contributing to the increased cardiovascular morbidity and mortality associated with acromegaly However, so far little is known about the impact of GH/IGF-1 on coagulation and fibrinolysis in acromegalic patients as possible risk factors for cardiovascular disease (CVD). To our knowledge, plasma tissue factor pathway inhibitor (TFPI) and thrombin-activatable fibrinolysis inhibitor (TAFI) levels in these patients have not been investigated. Therefore, the main purpose of this study was to evaluate the markers of endogenous coagulation/fibrinolysis, including TFPI and TAFI, and to investigate the relationships between GH/IGF-1 and these hemostatic parameters and serum lipid profile in patients with acromegaly.
A total of 22 patients with active acromegaly and 22 age-matched healthy controls were included in the study. Fibrinogen, factors V, VII, VIII, IX, and X activities, von-Willebrand factor (vWF), antithrombin III (AT III), protein C, protein S, tissue plasminogen activator (t-PA), tissue plasminogen activator inhibitor-I (PAI-1), TFPI and TAFI, as well as common lipid variables, were measured. The relationships between serum GH/IGF-1 and these hemostatic parameters were evaluated.
Compared with the control subjects, fibrinogen, AT III, t-PA, and PAI-1 were increased significantly in patients with acromegaly (P < 0.0001, P < 0.05, P < 0.01, and P < 0.0001, respectively), whereas protein S activity and TFPI levels were decreased significantly (P < 0.05 and P < 0.01, respectively). Plasma TAFI Ag levels did not significantly change in patients with acromegaly compared with the controls. In patients with acromegaly, serum GH levels were inversely correlated with TFPI and apo AI levels (r: -0.514, P: 0.029 and r: -0.602, P: 0.014, respectively). There was also a negative correlation between insulin-like growth factor-1 (IGF-1) and PAI-1 (r: -0.455, P: 0.045).
We found some important differences in the hemostatic parameters between the patients with acromegaly and healthy controls. Increased fibrinogen, t-PA, PAI-1 and decreased protein S and TFPI in acromegalic patients may represent a potential hypercoagulable and hypofibrinolytic state, which might augment the risk for atherosclerotic and atherothrombotic complications. Thus, disturbances of the hemostatic system and dyslipidemia may contribute to the excess mortality due to CVD seen in patients with acromegaly.
生长激素/胰岛素样生长因子-1（GH/IGF-1）分泌过多可能会影响导致肢端肥大症患者心血管发病率和死亡率增加的危险因素。然而，目前关于GH/IGF-1对肢端肥大症患者凝血和纤溶的影响（作为心血管疾病（CVD）的潜在危险因素）知之甚少。据我们所知，尚未对这些患者的血浆组织因子途径抑制物（TFPI）和凝血酶激活的纤溶抑制物（TAFI）水平进行研究。因此，本研究的主要目的是评估内源性凝血/纤溶标志物，包括TFPI和TAFI，并研究肢端肥大症患者中GH/IGF-1与这些止血参数及血清脂质谱之间的关系。
本研究共纳入22例活动期肢端肥大症患者和22例年龄匹配的健康对照者。检测纤维蛋白原、V、VII、VIII、IX和X因子活性、血管性血友病因子（vWF）、抗凝血酶III（AT III）、蛋白C、蛋白S、组织型纤溶酶原激活物（t-PA）、组织型纤溶酶原激活物抑制剂-1（PAI-1）、TFPI和TAFI以及常见脂质变量。评估血清GH/IGF-1与这些止血参数之间的关系。
与对照组相比，肢端肥大症患者的纤维蛋白原、AT III、t-PA和PAI-1显著升高（分别为P < 0.0001、P < 0.05、P < 0.01和P < 0.0001），而蛋白S活性和TFPI水平显著降低（分别为P < 0.05和P < 0.01）。与对照组相比，肢端肥大症患者的血浆TAFI抗原水平无显著变化。在肢端肥大症患者中，血清GH水平与TFPI和载脂蛋白AI水平呈负相关（r分别为-0.514，P为0.029；r为-0.602，P为0.014）。胰岛素样生长因子-1（IGF-1）与PAI-1之间也存在负相关（r为-0.455，P为0.045）。
我们发现肢端肥大症患者与健康对照者在止血参数方面存在一些重要差异。肢端肥大症患者纤维蛋白原、t-PA、PAI-1升高以及蛋白S和TFPI降低可能代表一种潜在的高凝和低纤溶状态，这可能会增加动脉粥样硬化和动脉粥样血栓形成并发症的风险。因此，止血系统紊乱和血脂异常可能导致肢端肥大症患者因CVD而出现过高的死亡率。
