垂体功能减退症合并肝硬化临床特征研究

Clinical Features of Hepatic Cirrhosis in Hypopituitarism

背景肝硬化是各种慢性肝病发展的晚期阶段,病因较多,出现并发症时死亡率较高,垂体功能减退导致激素缺乏与肝硬化关系的研究较少。目的分析8例垂体功能减退症合并肝硬化患者的临床特征,探讨垂体功能减退在肝硬化发病中的可能作用。方法选取2010年1月至2021年12月郑州大学第一附属医院收治的8例垂体功能减退症合并肝硬化患者,对其临床表现、实验室及影像学检查、治疗方法及随访结果进行回顾性分析。结果8例患者诊断垂体功能减退症时年龄为9~20岁,诊断肝硬化时年龄为16~24岁,中间相隔时间为3~14年。8例患者垂体功能减退症的病因为生殖细胞瘤手术(4例)、颅咽管瘤手术(2例)、鼻咽癌放疗(1例)及垂体柄阻断综合征(1例)。肝脏活检诊断为肝硬化2例,影像学诊断为肝硬化6例,诊断肝硬化前均未进行规范的激素替代治疗。乏力、纳差、外生殖器发育不良、身材矮小、反复上呼吸道感染、出血是最常见的临床表现。8例患者均有垂体-甲状腺轴、垂体-性腺轴、生长激素(GH)、胰岛素样生长因子1(IGF-1)、血常规、肝纤四项和影像学检查结果异常,7例患者表现为抗利尿激素及肝功能异常,6例患者表现为垂体-肾上腺轴、凝血功能和血脂异常。所有患者根据需要补充醋酸去氨加压素、甲状腺激素、氢化可的松及性激素,4例患者行GH替代治疗。随访1年后患者的白细胞计数、血小板计数、天冬氨酸氨基转移酶、碱性磷酸酶、总胆红素、间接胆红素、总胆固醇、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇、纤维蛋白原、肝纤四项较治疗前改善(P<0.05);随访1年后患者血红蛋白、丙氨酸氨基转移酶、谷氨酰转肽酶、直接胆红素、三酰甘油、凝血酶原时间、内源性凝血酶原时间、D-二聚体与治疗前比较,差异无统计学意义(P>0.05)。结论8例垂体功能减退症患者诊断肝硬化前均有数年的激素缺乏病程,均存在甲状腺激素、性激素、GH、IGF-1、血常规、肝纤四项和影像学检查异常,乏力、纳差、外生殖器发育不良、身材矮小、反复上呼吸道感染、出血是最常见的临床表现,规范的激素替代治疗1年可使白细胞计数、血小板计数、总胆固醇、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇、纤维蛋白原、肝纤四项等指标改善。

Background Hepatic cirrhosis represents the final stage for a wide variety of chronic liver diseases,which may be induced by numerous causes,and is associated with high mortality when complications arise.The relationships between hormone deficiencies due to hypopituitarism and hepatic cirrhosis have been rarely reported.Objective To analyze the clinical characteristics of 8 cases of hepatic cirrhosis secondary to hypopituitarism,and investigate the potential role of hypopituitarism in the development of hepatic cirrhosis.Methods Participants were 8 patients with hepatic cirrhosis secondary to hypopituitarism who were recruited from the First Affiliated Hospital of Zhengzhou University from January 2010 to December 2021.A retrospective analysis was conducted on their clinical manifestations,laboratory and imaging test result,treatments and follow-up results.Results The age at the diagnosis of hypopituitarism for all cases ranged from 9 to 20 years old,and that at the diagnosis of hepatic cirrhosis was 16 to 24 years old,with an interval of 3 to 14 years old.The causes of hypopituitarism were germ cell tumor surgery(4 cases),craniopharyngioma surgery(2 cases),radiotherapy for nasopharyngeal carcinoma(1 case)and pituitary stalk interruption syndrome(1 case).All cases received no standardized hormone replacement therapy before cirrhosis was diagnosed by biopsy(2 cases)or imaging(6 cases).Fatigue,anorexia,hypoplastic external genitalia,short stature,recurrent upper respiratory tract infection and bleeding were the most common clinical manifestations.All cases had abnormalities in pituitary-thyroid axis,pituitary-gonadal axis,growth hormone,insulin-like growth factor-1,routine blood markers,four markers of hepatic fibrosis and liver imaging results.Moreover,it was found that 7 cases were also with abnormalities in antidiuretic hormone and hepatic function,and 6 cases were with abnormalities in pituitary-adrenal axis,coagulation function and serum lipids.All patients received treatment with desmopress in acetate,thyroid hormone,hydrocortisone and sex hormones as necessary.Four patients also received growth hormone replacement therapy.One-year follow-up indicated that,all cases had significantly improved levels of leukocyte,platelet,aspartate aminotransferase,alkaline phosphatase,total bilirubin,indirect bilirubin,total cholesterol,low-density lipoprotein,high-density lipoprotein,fibrinogen and four markers of hepatic fibrosis after treatment(P<0.05).However,no significant post-treatment improvement was found in the levels of hemoglobin,alanine aminotransferase,gamma-glutamyl transpeptidase,direct bilirubin,triacylglycerol and D-dimer,and in prothrombin time and endogenous prothrombin potential(P>0.05).Conclusion All these 8 patients with hypopituitarism had hormone deficiency for several years before the diagnosis of hepatic cirrhosis,and abnormalities in thyroid hormone,sex hormone,growth hormone,insulin-like growth factor-1,routine blood markers,four markers of hepatic fibrosis and imaging results,with fatigue,anorexia,hypoplastic external genitalia,short stature,recurrent upper respiratory tract infection and bleeding as the most common clinical manifestations.One-year standardized hormone replacement therapy significantly improved the abnormalities in leukocyte,platelets,total cholesterol,high-density lipoprotein,low-density lipoprotein,fibrinogen and four markers of hepatic fibrosis.