Liver dysfunction in Turner's syndrome: prevalence, natural history and effect of exogenous oestrogen

Summary 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-β-oestradiol (E2) 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 (γ-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. Results  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.