Higher free triiodothyronine is associated with non-alcoholic fatty liver disease in euthyroid subjects: the Lifelines Cohort Study

Berg, Eline H. van den; Tienhoven-Wind, Lynnda J. N. van; Amini, Marzyeh; Schreuder, T.C.M.A.; Faber, Klaas Nico; Blokzijl, Hans; Dullaart, Robin P. F.

doi:10.1016/j.metabol.2016.11.002

Cited by 84 publications

(83 citation statements)

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“…3 Two Chinese studies and one Dutch study found a positive association between high-normal FT3 levels and NAFLD, where the latter used the fatty liver index to identify NAFLD. [8][9][10] Our results documented this positive association in euthyroid women but not in euthyroid men. We further combined NAFLD with ALT levels and with the FIB-4 index.…”

Section: Discussionsupporting

confidence: 50%

“…4,5 However, the conclusions from the studies regarding the association of free triiodothyronine (FT3), the bioactive form of thyroid hormones, with NAFLD in euthyroid subjects remained inconsistent. [6][7][8][9] Previous studies in Chinese 8,10 and Dutch people 9 showed that high-normal FT3 levels were associated with the risk of NAFLD, but other studies did not find the same association. 6,7 In addition, most of the studies showed that lower free thyroxine (FT4) 6,7,9 and higher TSH 7,9,10 levels within the normal range were associated with the risk of NAFLD in euthyroid adults.…”

Section: Introductionmentioning

confidence: 97%

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Free triiodothyronine is associated with the occurrence and remission of nonalcoholic fatty liver disease in euthyroid women

Chen

Hou

et al. 2019

Eur J Clin Investigation

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Background The association between nonalcoholic fatty liver disease (NAFLD) and free triiodothyronine (FT3) in euthyroid subjects was in dispute. We aimed to investigate this issue in a population‐based cohort study. Materials and methods A total of 3144 euthyroid subjects at baseline from the Shanghai Nicheng Atherosclerosis Study were selected for the cross‐sectional analysis, and 2089 subjects being followed up after 2.2 years were selected for the longitudinal analysis. NAFLD was diagnosed by ultrasound. The cut‐off point of elevated alanine aminotransferase (ALT) level was 40 U/L. The FIB‐4 index was used to assess the risk of advanced liver fibrosis. Results Age‐adjusted mean levels of FT3 and FT3/free thyroxine (FT4) ratio were higher in subjects with NAFLD than those without NAFLD and linearly increased with a higher risk of NAFLD progression (assessed by levels of ALT and FIB‐4 index) in euthyroid women but not in men. After adjustment for confounding variables, FT3 levels significantly increased with the presence of NAFLD (β = 0.1, P < 0.001) and linearly increased with a higher risk of NAFLD progression in euthyroid women. After a 2.2‐year follow‐up, FT3 levels increased with the occurrence of NAFLD (mean change percentage: 1.4%) and decreased with the remission of NAFLD (mean change percentage: −2.7%) in euthyroid women. Conclusions There are positive associations of FT3 levels with NAFLD and the risk of NAFLD progression in euthyroid women. The changes in FT3 levels with the alteration of NAFLD status may be an adaptive response to maintain energy and metabolic homeostasis.

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Section: Discussionsupporting

confidence: 50%

Section: Introductionmentioning

confidence: 97%

Free triiodothyronine is associated with the occurrence and remission of nonalcoholic fatty liver disease in euthyroid women

Chen

Hou

et al. 2019

Eur J Clin Investigation

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“…4,20 Free triiodothyronine has been positively related to body fat mass and various metabolic parameters. [21][22][23][24][25] A higher FT3 was associated with an enlarged waist circumference in study among U.S. people 22 and in the Lifelines Cohort study in the Netherlands. 25 Roef et al 24 reported T A B L E 5 Odds ratios for metabolic syndrome according to the deciles of TSH levels and FT3/FT4 ratios positive associations of FT3 with BMI, fat mass and insulin resistance assessed by HOMA-IR in healthy euthyroid young men.…”

Section: Ft3/ft4 Ratio Can Predict Metabolic Syndrome Better Than Tshmentioning

confidence: 81%

Free triiodothyronine/free thyroxine ratio rather than thyrotropin is more associated with metabolic parameters in healthy euthyroid adult subjects

Park

Jung

et al. 2017

Clinical Endocrinology

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“…The effect was mediated by body composition changes and by the fat-associated hormone leptin rather than androgen deficiency. Another study interrelated non-alcoholic fatty liver disease with higher fT3 concentrations in euthyroid subjects, probably consequent to central obesity (197). Both central and peripheral components of the feedback loop are apparently involved in the reactive adjustments to obesity (Figure 7).…”

Section: Thyroid Allostasis In Various Physiological and Pathologicalmentioning

confidence: 99%

Thyroid Allostasis–Adaptive Responses of Thyrotropic Feedback Control to Conditions of Strain, Stress, and Developmental Programming

Hoermann²,

et al. 2017

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The hypothalamus–pituitary–thyroid feedback control is a dynamic, adaptive system. In situations of illness and deprivation of energy representing type 1 allostasis, the stress response operates to alter both its set point and peripheral transfer parameters. In contrast, type 2 allostatic load, typically effective in psychosocial stress, pregnancy, metabolic syndrome, and adaptation to cold, produces a nearly opposite phenotype of predictive plasticity. The non-thyroidal illness syndrome (NTIS) or thyroid allostasis in critical illness, tumors, uremia, and starvation (TACITUS), commonly observed in hospitalized patients, displays a historically well-studied pattern of allostatic thyroid response. This is characterized by decreased total and free thyroid hormone concentrations and varying levels of thyroid-stimulating hormone (TSH) ranging from decreased (in severe cases) to normal or even elevated (mainly in the recovery phase) TSH concentrations. An acute versus chronic stage (wasting syndrome) of TACITUS can be discerned. The two types differ in molecular mechanisms and prognosis. The acute adaptation of thyroid hormone metabolism to critical illness may prove beneficial to the organism, whereas the far more complex molecular alterations associated with chronic illness frequently lead to allostatic overload. The latter is associated with poor outcome, independently of the underlying disease. Adaptive responses of thyroid homeostasis extend to alterations in thyroid hormone concentrations during fetal life, periods of weight gain or loss, thermoregulation, physical exercise, and psychiatric diseases. The various forms of thyroid allostasis pose serious problems in differential diagnosis of thyroid disease. This review article provides an overview of physiological mechanisms as well as major diagnostic and therapeutic implications of thyroid allostasis under a variety of developmental and straining conditions.

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Higher free triiodothyronine is associated with non-alcoholic fatty liver disease in euthyroid subjects: the Lifelines Cohort Study

Abstract: Euthyroid subjects with suspected NAFLD are characterized by higher FT3, lower FT4 and higher FT3/FT4 ratio, probably consequent to central obesity.

Cited by 84 publications

References 50 publications

Free triiodothyronine is associated with the occurrence and remission of nonalcoholic fatty liver disease in euthyroid women

Free triiodothyronine is associated with the occurrence and remission of nonalcoholic fatty liver disease in euthyroid women

Free triiodothyronine/free thyroxine ratio rather than thyrotropin is more associated with metabolic parameters in healthy euthyroid adult subjects

Thyroid Allostasis–Adaptive Responses of Thyrotropic Feedback Control to Conditions of Strain, Stress, and Developmental Programming

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