Background: While cardiac complications, short stature, and infertility are often discussed in the context of Turner Syndrome (TS), abnormalities of liver function are less well described. In order to address this gap in knowledge, we sought to better characterize hepatic abnormalities in youth with TS. Methods: PEDSnet is a collaboration across 7 major US pediatric institutions that unifies electronic medical data including diagnoses, prescriptions, and laboratory measurements for over 6 million children. 2,145 females with a diagnosis of TS were matched to 8,580 females without TS (1:4 ratio) on site, race (68% White), ethnicity (15% Hispanic), payer source, year of birth, age at most recent visit (median 14 years), and duration of care (mean 8 years). Outcomes of interest included highest recorded liver enzyme values (AST and ALT) categorized as normal or above the upper limit of normal (ULN) defined as >95th percentile for their age, and specific liver diagnoses. Proportions were compared between the cohorts using odds ratios (OR) and 95% confidence intervals (CI) from a generalized estimating equations approach. Multinomial logistic regression was conducted to investigate potential risk factors for liver abnormalities within the TS cohort. Results: Out of 1,159 girls with TS who had liver enzymes recorded in PEDSnet, 58% had at least one AST or ALT above the ULN. TS patients were more likely to have enzymes 1-2 times ULN (OR: 1.7, 95% CI: 1.4-1.9), more likely to be in the 2-3 times ULN category (OR: 2.7, 95% CI: 1.7-3.3), and more likely to be in the >3 times ULN category (OR: 1.7, 95% CI: 1.3-2.2) compared to girls without TS. TS patients were also more likely to have any liver diagnosis (OR: 2.4, 95% CI: 1.7-3.3), including significantly higher risk of fatty liver disease (OR: 1.9, 95% CI: 1.1-3.2), hepatitis (OR: 3.7, 95% CI: 1.9-7.1), cirrhosis/fibrosis (OR: 5.8, 95% CI: 1.3-25.0), and liver tumor/malignancy (OR: 4.8, 95% CI: 1.4-17.0). In the multinomial model, age, BMI, and the presence of a thyroid condition, cardiovascular diagnosis, or diabetes significantly (p < 0.05) increased the risk for elevated liver enzymes in girls with TS, while mosaicism, estrogen prescription, and celiac disease did not. Stratifying by age groups, over 40% of girls with TS had ALT elevations (24% > 2 times ULN, some with diagnosed liver conditions) under age 10, when liver screening is officially recommended per TS guidelines. Conclusions: Prevalence of elevated liver enzymes and diagnoses of liver disease are significantly higher in youth with TS vs. controls, emphasizing the need for clinical monitoring and additional research. Given the high percentage of girls <10 years of age with clinically significant liver enzyme elevation, there should be strong consideration for modifying the current guidelines to start screening earlier.
