Endocrine Abnormalities in Hereditary Disorders of Connective Tissue

我们分析了2003-086方案中约200名诊断为Ehlers Danlos综合征、纤维肌肉发育不良和马凡氏综合征的参与者的血浆样本。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%患有埃勒斯-丹洛斯综合征和马凡氏综合征的男性睾丸激素水平异常低。相应的LH和FSH值较低，提示垂体功能异常而非性腺功能障碍。性激素结合球蛋白升高见于上述所有诊断的女性。结缔组织疾病患儿的IGF-1水平较低。此外，与年龄和性别匹配的对照组相比，血管型Ehlers Danlos患者的瘦素水平升高。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潜在血管病理的保护性反应，还是与血管不良事件的发生有因果关系。纠正这些异常的决定取决于更好地理解这些发现的机制。

We have analyzed plasma samples from approximately 200 of the participants enrolled in 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 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.