title: Higher free triiodothyronine is associated with non-alcoholic fatty liver disease in euthyroid subjects: the Lifelines Cohort Study.
abstract: OBJECTIVE
  Overt hypothyroidism confers an increased risk of non-alcoholic fatty liver disease (NAFLD). The liver plays a crucial role in the metabolism of cholesterol and triglycerides; thyroid hormones interact on hepatic lipid homeostasis. Thyroid function within the euthyroid range affects a number of health issues, including atherosclerosis development and biochemical markers of increased cardiovascular risk. However, the association of thyroid hormones with NAFLD in euthyroid subjects has not been unequivocally established. We therefore determined associations of thyroid hormone parameters with NAFLD among euthyroid subjects.
  
  
  METHODS
  The study was conducted in the Lifelines Cohort Study, a population-based cohort study of participants living in the North of the Netherlands. Only euthyroid subjects (thyroid-stimulating hormone (TSH) 0.5-4.0mU/L, free thyroxine (FT4) 11-19.5pmol/L and free triiodothyronine (FT3) 4.4-6.7pmol/L) older than 18years were included. Exclusion criteria were participants with excessive alcohol use, known hepatitis or cirrhosis, liver functions ≥ three times the upper limit, current cancer, non-white ancestry, previous or current use of thyroid medication and current use of lipid or glucose lowering medication. A priori defined liver biochemistry, thyroid function parameters and metabolic syndrome (MetS) were studied. NAFLD was defined by using the validated Fatty Liver Index (FLI); FLI≥60 was categorized as NAFLD. A P<0.01 was considered significant.
  
  
  RESULTS
  FLI≥60 was found in 4274 (21.1%) of 20,289 individuals (62.1% male, median age 46years) with increased prevalence of MetS (P<0.0001). In age- and sex-adjusted analysis FLI≥60 was independently associated with a higher FT3 (OR 1.34, 95% CI 1.29-1.39, per SD increment, P<0.0001) and a lower FT4 (OR 0.73, 95% CI 0.70-0.75, P<0.0001) but not by TSH. The strongest association was found for the FT3/FT4 ratio (OR 1.44, 95% CI 1.39-1.49, P<0.0001). These associations remained similar after additional adjustment for the presence of MetS. In subjects with enlarged waist circumference, TSH and FT4 were lower while FT3 was higher, resulting in an increased FT3/FT4 ratio (P<0.0001).
  
  
  CONCLUSIONS
  Euthyroid subjects with suspected NAFLD are characterized by higher FT3, lower FT4 and higher FT3/FT4 ratio, probably consequent to central obesity.
authors.affiliation: Department of Gastroenterology and Hepatology, University of Groningen and University Medical Center Groningen, The Netherlands. Electronic address: e.h.van.den.berg@umcg.nl.
authors.forename: Eline H
authors.initials: EH
authors.lastname: van den Berg
authors.affiliation: Department of Endocrinology, University of Groningen and University Medical Center Groningen, The Netherlands.
authors.forename: Lynnda J N
authors.initials: LJ
authors.lastname: van Tienhoven-Wind
authors.affiliation: Department of Epidemiology, University of Groningen, and University Medical Center Groningen, The Netherlands.
authors.forename: Marzyeh
authors.initials: M
authors.lastname: Amini
authors.affiliation: Department of Gastroenterology and Hepatology, University of Groningen and University Medical Center Groningen, The Netherlands.
authors.forename: Tim C M A
authors.initials: TC
authors.lastname: Schreuder
authors.affiliation: Department of Gastroenterology and Hepatology, University of Groningen and University Medical Center Groningen, The Netherlands.
authors.forename: Klaas Nico
authors.initials: KN
authors.lastname: Faber
authors.affiliation: Department of Gastroenterology and Hepatology, University of Groningen and University Medical Center Groningen, The Netherlands.
authors.forename: Hans
authors.initials: H
authors.lastname: Blokzijl
authors.affiliation: Department of Endocrinology, University of Groningen and University Medical Center Groningen, The Netherlands.
authors.forename: Robin P F
authors.initials: RP
authors.lastname: Dullaart
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D008111:Liver Function Tests; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood; D008875:Middle Aged; D009426:Netherlands / Q000453:epidemiology; D065626:Non-alcoholic Fatty Liver Disease / Q000097:blood* / Q000453:epidemiology; D012307:Risk Factors; D013961:Thyroid Gland; D013972:Thyrotropin / Q000097:blood; D013974:Thyroxine / Q000097:blood; D014284:Triiodothyronine / Q000097:blood*; D055815:Young Adult
chemical_list: D014284:Triiodothyronine; D013972:Thyrotropin; D013974:Thyroxine
keywords: Central obesity; Euthyroidism; Free thyroxine; Free triiodothyronine; Non-alcoholic fatty liver disease