Liver dysfunction in Turner's syndrome: prevalence, natural history and effect of exogenous oestrogen
Liver dysfunction in Turner's syndrome: prevalence, natural history and effect of exogenous oestrogen
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DOI：
10.1111/j.1365-2265.2008.03203.x
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发表时间：
2008-08-01
影响因子：
3.2
通讯作者：
Conway, Gerard S.
中科院分区：
文献类型：
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作者：
Koulouri, Olympia;Ostberg, Julia;Conway, Gerard S.
目的肝酶升高是Turner综合征(TS)的常见特征，但其病因尚不清楚。我们研究了一大批患有TS的妇女的肝功能，并测试了增加激素替代疗法(HRT)剂量对肝功能测试(LFT)的影响。设计和患者在三项研究中评估了LFT。对125名女性(中位年龄：31岁)的肝功能进行了横断面回顾，对30名女性(平均随访时间：8年)进行了纵向研究，并对14名患有TS的女性和11名性腺功能低下的女性进行了剂量-反应研究，这些女性每天服用1，2和4 mg的周期性制剂，每天服用1，2和4 mg的周期性制剂。临床特征、雌激素使用和代谢参数与肝酶(伽马谷氨酰转移酶(GGT)、丙氨酸氨基转移酶(ALT)和碱性磷酸酶(ALP))、白蛋白和胆红素进行比较。在剂量-反应研究的每个治疗间隔期间也测量了LFT。在横断面研究中寻求肝脏自身免疫。结果与对照人群相比，与参考范围相比，91%的TS妇女表现出肝酶升高，年发病率为2.1%。LFTs与胆固醇(P<；0.001)、体重指数(P=0.004)和雌激素治疗类型(P=0.04)呈正相关。随着HRT剂量的增加，GGT、ALT、胆红素和白蛋白均显著下降。没有发现肝脏自身免疫过度的证据。结论使用参考范围而不是匹配的对照，可能低估了TS患者肝酶升高的发生率。与口服避孕药(OCP)相比，肥胖和高脂血症与LFTs升高以及HRT的使用有关。外源性雌激素作为OCP和HRT均可改善肝功能。TS的肝功能障碍很可能是肝脏脂肪变性的一种形式，现在有干预试验的迹象。
Objectives Raised liver enzymes are a common feature of Turner's syndrome (TS), but the cause remains unclear. We studied the hepatic function in a large cohort of women with TS and tested the effect of increasing doses of hormone replacement therapy (HRT) on liver function tests (LFTs).Design and patients LFTs were assessed in three studies. A cross-sectional review of liver function of 125 women (median age: 31 years), a longitudinal study of 30 women (mean follow-up period: 8 years) and a dose-response study of 14 women with TS and 11 controls with hypogonadism, who received oral 17-beta-oestradiol (E-2) 1, 2 and 4 mg daily in a cyclical formulation for 12 weeks each.Measurements Clinical features, oestrogen use and metabolic parameters were compared to liver enzymes (gamma-glutamyl transferase (GGT), alanine aminotransferase (ALT) and alkaline phosphatase (ALP)), albumin and bilirubin. LFTs were also measured during each treatment interval of the dose-response study. Hepatic autoimmunity was sought in the cross-sectional study.Resultsn When compared to the control population, as opposed to reference ranges, 91% of women with TS demonstrated liver enzyme elevation, with a yearly incidence of 2.1%. LFTs correlated positively with cholesterol (P < 0.001), BMI (P = 0.004) and type of oestrogen therapy (P = 0.04). Increasing doses of HRT resulted in a significant decrease in GGT, ALT, bilirubin and albumin. No evidence of excessive hepatic autoimmunity was found.Conclusion The prevalence of raised liver enzymes in TS may have been underestimated by the use of reference ranges rather than matched controls. Obesity and hyperlipidaemia are associated with raised LFTs, as well as the use of HRT compared to the oral contraceptive pill (OCP). Exogenous oestrogen both as OCP and HRT improves liver function. Liver dysfunction in TS is likely to be a form of hepatic steatosis and intervention trials are now indicated.