Thyroid Function and the Risk of Nonalcoholic Fatty Liver Disease: The Rotterdam Study.
Although thyroid function is associated with several risk factors of nonalcoholic fatty liver disease (NAFLD), its role in NAFLD development remains unclear.



We aimed to prospectively investigate the association between variations in thyroid function and NAFLD.



The Rotterdam Study, a large population-based, prospective cohort study.



Participants with thyroid function measurements at baseline and NAFLD data (ie, at baseline fatty liver index/at follow-up ultrasound) were eligible. Transient elastography was performed to assess the presence of fibrosis in patients with NAFLD, using the liver stiffness measurements more than or equal to 8 kPa as cutoff for clinically relevant fibrosis. The association between thyroid parameters and incident NAFLD was explored by using logistic regression models.



A total of 9419 participants (mean age, 64.75 y) were included. The median follow-up time was 10.04 years (interquartile range, 5.70-10.88 y). After adjusting for age, sex, cohort, follow-up time, use of hypolipidemic drugs, and cardiovascular risk factors, higher free T4 levels were associated with a decreased risk of NAFLD (odds ratio, 0.42; 95% confidence interval [CI], 0.28-0.63). In line, higher TSH levels were associated with an increased risk of having clinically relevant fibrosis in NAFLD (odds ratio, 1.49; CI, 1.04-2.15). Compared with euthyroidism, hypothyroidism was associated with a 1.24-fold higher NAFLD risk (CI, 1.01-1.53). Moreover, NAFLD risk decreased gradually from hypothyroidism to hyperthyroidism (P for trend = .003).



Lower thyroid function is associated with an increased NAFLD risk. These findings may lead to new avenues regarding NAFLD prevention and treatment.
Department of Internal Medicine (A.B., L.C., R.P.P.), Erasmus University Medical Center, 3015 GE, Rotterdam, The Netherlands; Rotterdam Thyroid Center (A.B., L.C., R.P.P.), Erasmus University Medical Center, 3015 GE, Rotterdam, The Netherlands; Department of Epidemiology (A.B., L.C., E.P.C.P., A.H., A.D., O.H.F., S.D.M., R.P.P.), Erasmus University Medical Center, 3015 GE, Rotterdam, The Netherlands; Department of Gastroenterology and Hepatology (E.P.C.P., H.L.A.J., S.D.M.), Erasmus University Medical Center, 3015 GE, Rotterdam, The Netherlands; and Toronto Centre for Liver Disease (H.L.A.J.), Toronto Western and General Hospital, University Health Network, Toronto, Ontario, M5G 2C4 Canada.
Arjola
A
Bano
Department of Internal Medicine (A.B., L.C., R.P.P.), Erasmus University Medical Center, 3015 GE, Rotterdam, The Netherlands; Rotterdam Thyroid Center (A.B., L.C., R.P.P.), Erasmus University Medical Center, 3015 GE, Rotterdam, The Netherlands; Department of Epidemiology (A.B., L.C., E.P.C.P., A.H., A.D., O.H.F., S.D.M., R.P.P.), Erasmus University Medical Center, 3015 GE, Rotterdam, The Netherlands; Department of Gastroenterology and Hepatology (E.P.C.P., H.L.A.J., S.D.M.), Erasmus University Medical Center, 3015 GE, Rotterdam, The Netherlands; and Toronto Centre for Liver Disease (H.L.A.J.), Toronto Western and General Hospital, University Health Network, Toronto, Ontario, M5G 2C4 Canada.
Layal
L
Chaker
Department of Internal Medicine (A.B., L.C., R.P.P.), Erasmus University Medical Center, 3015 GE, Rotterdam, The Netherlands; Rotterdam Thyroid Center (A.B., L.C., R.P.P.), Erasmus University Medical Center, 3015 GE, Rotterdam, The Netherlands; Department of Epidemiology (A.B., L.C., E.P.C.P., A.H., A.D., O.H.F., S.D.M., R.P.P.), Erasmus University Medical Center, 3015 GE, Rotterdam, The Netherlands; Department of Gastroenterology and Hepatology (E.P.C.P., H.L.A.J., S.D.M.), Erasmus University Medical Center, 3015 GE, Rotterdam, The Netherlands; and Toronto Centre for Liver Disease (H.L.A.J.), Toronto Western and General Hospital, University Health Network, Toronto, Ontario, M5G 2C4 Canada.
Elisabeth P C
EP
Plompen
Department of Internal Medicine (A.B., L.C., R.P.P.), Erasmus University Medical Center, 3015 GE, Rotterdam, The Netherlands; Rotterdam Thyroid Center (A.B., L.C., R.P.P.), Erasmus University Medical Center, 3015 GE, Rotterdam, The Netherlands; Department of Epidemiology (A.B., L.C., E.P.C.P., A.H., A.D., O.H.F., S.D.M., R.P.P.), Erasmus University Medical Center, 3015 GE, Rotterdam, The Netherlands; Department of Gastroenterology and Hepatology (E.P.C.P., H.L.A.J., S.D.M.), Erasmus University Medical Center, 3015 GE, Rotterdam, The Netherlands; and Toronto Centre for Liver Disease (H.L.A.J.), Toronto Western and General Hospital, University Health Network, Toronto, Ontario, M5G 2C4 Canada.
Albert
A
Hofman
Department of Internal Medicine (A.B., L.C., R.P.P.), Erasmus University Medical Center, 3015 GE, Rotterdam, The Netherlands; Rotterdam Thyroid Center (A.B., L.C., R.P.P.), Erasmus University Medical Center, 3015 GE, Rotterdam, The Netherlands; Department of Epidemiology (A.B., L.C., E.P.C.P., A.H., A.D., O.H.F., S.D.M., R.P.P.), Erasmus University Medical Center, 3015 GE, Rotterdam, The Netherlands; Department of Gastroenterology and Hepatology (E.P.C.P., H.L.A.J., S.D.M.), Erasmus University Medical Center, 3015 GE, Rotterdam, The Netherlands; and Toronto Centre for Liver Disease (H.L.A.J.), Toronto Western and General Hospital, University Health Network, Toronto, Ontario, M5G 2C4 Canada.
Abbas
A
Dehghan
Department of Internal Medicine (A.B., L.C., R.P.P.), Erasmus University Medical Center, 3015 GE, Rotterdam, The Netherlands; Rotterdam Thyroid Center (A.B., L.C., R.P.P.), Erasmus University Medical Center, 3015 GE, Rotterdam, The Netherlands; Department of Epidemiology (A.B., L.C., E.P.C.P., A.H., A.D., O.H.F., S.D.M., R.P.P.), Erasmus University Medical Center, 3015 GE, Rotterdam, The Netherlands; Department of Gastroenterology and Hepatology (E.P.C.P., H.L.A.J., S.D.M.), Erasmus University Medical Center, 3015 GE, Rotterdam, The Netherlands; and Toronto Centre for Liver Disease (H.L.A.J.), Toronto Western and General Hospital, University Health Network, Toronto, Ontario, M5G 2C4 Canada.
Oscar H
OH
Franco
Department of Internal Medicine (A.B., L.C., R.P.P.), Erasmus University Medical Center, 3015 GE, Rotterdam, The Netherlands; Rotterdam Thyroid Center (A.B., L.C., R.P.P.), Erasmus University Medical Center, 3015 GE, Rotterdam, The Netherlands; Department of Epidemiology (A.B., L.C., E.P.C.P., A.H., A.D., O.H.F., S.D.M., R.P.P.), Erasmus University Medical Center, 3015 GE, Rotterdam, The Netherlands; Department of Gastroenterology and Hepatology (E.P.C.P., H.L.A.J., S.D.M.), Erasmus University Medical Center, 3015 GE, Rotterdam, The Netherlands; and Toronto Centre for Liver Disease (H.L.A.J.), Toronto Western and General Hospital, University Health Network, Toronto, Ontario, M5G 2C4 Canada.
Harry L A
HL
Janssen
Department of Internal Medicine (A.B., L.C., R.P.P.), Erasmus University Medical Center, 3015 GE, Rotterdam, The Netherlands; Rotterdam Thyroid Center (A.B., L.C., R.P.P.), Erasmus University Medical Center, 3015 GE, Rotterdam, The Netherlands; Department of Epidemiology (A.B., L.C., E.P.C.P., A.H., A.D., O.H.F., S.D.M., R.P.P.), Erasmus University Medical Center, 3015 GE, Rotterdam, The Netherlands; Department of Gastroenterology and Hepatology (E.P.C.P., H.L.A.J., S.D.M.), Erasmus University Medical Center, 3015 GE, Rotterdam, The Netherlands; and Toronto Centre for Liver Disease (H.L.A.J.), Toronto Western and General Hospital, University Health Network, Toronto, Ontario, M5G 2C4 Canada.
Sarwa
S
Darwish Murad
Department of Internal Medicine (A.B., L.C., R.P.P.), Erasmus University Medical Center, 3015 GE, Rotterdam, The Netherlands; Rotterdam Thyroid Center (A.B., L.C., R.P.P.), Erasmus University Medical Center, 3015 GE, Rotterdam, The Netherlands; Department of Epidemiology (A.B., L.C., E.P.C.P., A.H., A.D., O.H.F., S.D.M., R.P.P.), Erasmus University Medical Center, 3015 GE, Rotterdam, The Netherlands; Department of Gastroenterology and Hepatology (E.P.C.P., H.L.A.J., S.D.M.), Erasmus University Medical Center, 3015 GE, Rotterdam, The Netherlands; and Toronto Centre for Liver Disease (H.L.A.J.), Toronto Western and General Hospital, University Health Network, Toronto, Ontario, M5G 2C4 Canada.
Robin P
RP
Peeters
D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009426:Netherlands / Q000453:epidemiology; D065626:Non-alcoholic Fatty Liver Disease / Q000150:complications* / Q000175:diagnosis / Q000453:epidemiology*; D013959:Thyroid Diseases / Q000150:complications* / Q000175:diagnosis / Q000453:epidemiology*; D013960:Thyroid Function Tests; D014463:Ultrasonography