Women with Turner syndrome (TS), one of the commonest sex chromosomal abnormalities, are at increased risk of impaired liver function as manifested by elevated liver enzymes, but its clinical significance remains uncertain. Factors contributing to increased liver function tests (LFTs) were investigated in 3 studies:
* A cross-sectional review of liver function in 125 women with TS whose median age was 31 years.
* A longitudinal study of 30 women with TS who were followed-up for 8 years on average.
* A dose-response study of 14 women with TS and 11 control women with hypogonadism who received 17-β-estradiol in doses of 1, 2, and 4 mg daily cyclically for 12 weeks each.
The enzymes measured included γ-glutamyl transferase (GGT), alanine aminotransferase (ALT), and alkaline phosphatase.
Compared with a control population, 91% of women with TS had elevated liver enzymes. The annual incidence was 2.1%. In the cross-sectional study, the enzyme most frequently elevated was GGT. LFTs correlated positively with cholesterol levels and body mass index. Increasing doses of hormone replacement therapy were associated with significant reductions in GGT, ALT, bilirubin, and albumin. Exogenous estrogen, whether in the form of oral contraception or HRT, improved liver function. There was no evidence of hepatic autoimmunity apart from anti-smooth muscle antibodies in 2.2% of individuals.
Previous studies using reference ranges rather than matched control subjects may have underestimated the frequency of elevated liver enzymes in women with TS. The investigators believe that hepatic dysfunction in women with TS is probably a form of hepatic steatosis. Estrogen therapy should continue despite the presence of liver dysfunction, and there may be reason to increase the estrogen replacement dose.