Sartorio A, Cattaneo M, Bucciarelli P, Bottasso B, Porretti S, Epaminonda P, Faglia G, Arosio M
Italian Institute for Auxology IRCCS, Division of Metabolic Diseases, Piancavallo (VB), and Growth Disorders Center, Milano, Italy.
Exp Clin Endocrinol Diabetes. 2000;108(7):486-92. doi: 10.1055/s-2000-8145.
Alterations of coagulation and fibrinolytic systems might contribute to the increased cardiovascular and cerebrovascular mortality observed in patients with both chronic growth hormone (GH) excess (acromegaly) and deficiency (GHD). However, contrasting results have been so far reported. To assess the importance of GH in modulating haemostatic system, several haemostatic variables in patients with GHD and acromegaly were measured. Twenty-four adult patients with GHD (8 childhood- and 16 adult-onset; age: 41+/-12 years, insulin like growth factor-I, IGF-I: 6.7+/-4 nmol/L), 10 non-diabetic acromegalic patients (age: 39+/-15 years; IGF-I: 109+/-37 nmol/L) and 64 healthy volunteers age- and sex-matched with cases were studied. The plasma levels of tissue-type plasminogen activator antigen (t-PA), prothrombin fragment 1+2 (F1+2) and thrombin-antithrombin complex (TAT) were measured by ELISA. Plasminogen activator inhibitor type I (PAI-1) was measured by an immunoactivity assay and fibrinogen by von Clauss method. GH levels were measured by IFMA and IGF-I by RIA. GHD patients had higher PAI-1 (12.7+/-16.7 vs 4.8+/-5.3 U/ml, p<0.01), fibrinogen (363+/-104 vs 291+/-71 mg/dL, p< 0.05) and TAT levels (6.8+/-9 vs 3.6+/-2.8 ng/ml, p<0.05) than controls. Taking the 95th pecentile of the normal distribution in the control group as the cut-off point for normal plasma levels of the haemostatic variables, high PAI levels were found in 25% of patients with GHD (P<0.01), while high fibrinogen and TAT levels were observed in 21% (P<0.05). The alterations were mostly present in patients with adult-onset GHD, with the exception of hyperfibrinogenaemia which was equally present in adult- and childhood-onset patients. Acromegalic patients had higher mean fibrinogen levels than controls (398+/-111 vs 291+/-71 mg/dL, p< 0.05), 40% having hyperfibrinogenaemia (P<0.01, vs controls). They also had t-PA levels lower than controls and GHD. No correlations between hormonal and haemostatic variables were found. Body mass index and waist to hip ratio correlated positively with PAI-1 levels in GHD patients only. In conclusion, this study shows that several abnormalities of coagulation variables (increased PAI-1. fibrinogen and TAT levels) are present in patients with GHD, while only hyperfibrinogenaemia is found in patients with acromegaly. These changes do not appear to be directly related to IGF-I levels or to the degree of GH deficiency/excess. However, these abnormalities may be an additional trigger for the development of coronary heart disease and thromboembolic complications mostly in patients with GHD.
凝血和纤溶系统的改变可能是导致慢性生长激素（GH）分泌过多（肢端肥大症）和分泌不足（GHD）患者心血管和脑血管死亡率增加的原因。然而，迄今为止报道的结果相互矛盾。为了评估GH在调节止血系统中的重要性，对GHD和肢端肥大症患者的几个止血变量进行了测量。研究了24例成年GHD患者（8例儿童期发病和16例成年期发病；年龄：41±12岁，胰岛素样生长因子-I，IGF-I：6.7±4 nmol/L）、10例非糖尿病肢端肥大症患者（年龄：39±15岁；IGF-I：109±37 nmol/L）以及64名年龄和性别与病例匹配的健康志愿者。采用酶联免疫吸附测定法（ELISA）测量血浆组织型纤溶酶原激活物抗原（t-PA）、凝血酶原片段1+2（F1+2）和凝血酶-抗凝血酶复合物（TAT）的水平。采用免疫活性测定法测量纤溶酶原激活物抑制剂I型（PAI-1），采用冯·克劳斯法测量纤维蛋白原。采用免疫荧光法测量GH水平，采用放射免疫分析法测量IGF-I水平。GHD患者的PAI-1水平（12.7±16.7 vs 4.8±5.3 U/ml，p<0.01）、纤维蛋白原水平（363±104 vs 291±71 mg/dL，p<0.05）和TAT水平（6.8±9 vs 3.6±2.8 ng/ml，p<0.05）均高于对照组。以对照组正常分布的第95百分位数作为止血变量正常血浆水平的截断点，发现25%的GHD患者PAI水平较高（P<0.01），而21%的患者纤维蛋白原和TAT水平较高（P<0.05）。这些改变主要出现在成年期发病的GHD患者中，高纤维蛋白原血症在成年期和儿童期发病患者中同样存在。肢端肥大症患者的平均纤维蛋白原水平高于对照组（398±111 vs 291±71 mg/dL，p<0.05），40%的患者患有高纤维蛋白原血症（P<0.01，与对照组相比）。他们的t-PA水平也低于对照组和GHD患者。未发现激素与止血变量之间存在相关性。仅在GHD患者中，体重指数和腰臀比与PAI-1水平呈正相关。总之，本研究表明，GHD患者存在几种凝血变量异常（PAI-1、纤维蛋白原和TAT水平升高），而肢端肥大症患者仅存在高纤维蛋白原血症。这些变化似乎与IGF-I水平或GH缺乏/过量程度无直接关系。然而，这些异常可能是冠心病和血栓栓塞并发症发生发展的另一个触发因素，主要见于GHD患者。
