Endocrine Abnormalities in Hereditary Disorders of Connective Tissue

我们分析了大约200名参与IRB批准的方案2003-086的参与者的血浆样本，这些参与者被诊断为埃勒斯-丹洛斯综合征、纤维肌发育不良和马凡综合征。这些诊断与不良心血管事件和导致过早死亡的早期血管老化有关。感兴趣的内分泌标志物包括游离和总睾酮、性激素结合球蛋白、雌酮、雌二醇、IGF-1、LH和FSH。大约30%的Ehlers Danlos综合征和Marfan综合征患者的睾酮水平异常低。相应的LH和FSH值较低，表明垂体功能异常，而不是性腺功能障碍。升高的性激素结合球蛋白见于所有上述诊断的女性。患有结缔组织疾病的儿童的IGF-1循环值较低。此外，与年龄和性别匹配的对照组相比，具有血管形式的Ehlers Danlos的患者具有升高的瘦素水平。内分泌异常与低骨密度和不良心血管预后相关。我们计划研究这些发现的病理机制。目前尚不清楚这些异常是对基础血管病理学的保护性反应，还是与不良血管事件的发生有因果关系。纠正异常的决定取决于对这些发现的机制的更好理解。

We have analyzed plasma samples from approximately 200 of the participants enrolled in IRB-approved protocol 2003-086 with diagnoses of Ehlers Danlos Syndrome, Fibromuscular Dysplasia and Marfan Syndrome. These diagnoses are associated with adverse cardiovascular events and early vascular aging causing premature death. The endocrine markers of interest include free and total testosterone, sex hormone binding globulin, estrone, estrodiol, IGF-1, LH and FSH. Approximately 30% of men with Ehlers Danlos syndrome and Marfan syndrome have abnormally low testosterone levels. Corresponding LH and FSH values are low, indicating abnormal pituitary function as opposed to gonadal dysfunction. Elevated Sex Hormone Binding Globulin is seen in women will all the above diagnoses. Children with connective tissue disorders have low circulating values of IGF-1. In addition, patients with the vascular form of Ehlers Danlos have elevated leptin levels as compared to age and sex matched controls. The endocrine abnormalities are correlated with low bone density and poor cardiovascular prognosis. We plan to investigate the pathological mechanisms of these findings. It is not yet clear that these abnormalities are protective responses to the underlying vascular pathology versus causally involved in the development of the adverse vascular events. The decision to correct the abnormalities is dependent on better understanding of the mechanisms of these findings.