Central Sensitivity to Free Triiodothyronine With MAFLD and Its Progression to Liver Fibrosis in Euthyroid Adults

Abstract

Background Impaired sensitivity to thyroid hormones has been demonstrated to be positively associated with the prevalence of metabolic disorders. However, the relationship between sensitivity to thyroid hormones and metabolic dysfunction-associated fatty liver disease (MAFLD) and liver fibrosis remained unclear. We aimed to determine the associations of thyroid hormone sensitivity indices with MAFLD and its progression to liver fibrosis in Chinese euthyroid adults. Methods 7906 euthyroid adults were included in this community-based study. We calculated the thyroid sensitivity indices, including free triiodothyronine to free thyroxine (FT3/FT4) ratio, thyroid feedback quantile-based index by FT4 (TFQIFT4), and thyroid feedback quantile-based index by FT3 (TFQIFT3), indicate peripheral and central thyroid hormone sensitivity respectively. Liver steatosis and fibrosis were diagnosed by vibration-controlled transient elastography (VCTE). The multivariable logistic/linear regression and restricted cubic spline (RCS) analysis were conducted. Results Compared with participants in quartile 1st (Q1), the prevalence of MAFLD increased by 62% in quartile 4th (Q4) of FT3/FT4 ratio (OR 1.62, 95% CI (1.38, 1.91)) and by 40% in Q4 of TFQIFT3 (OR 1.40, 95% CI (1.18, 1.65)) (both P < 0.05). No associations between TFQIFT4 and the prevalence of MAFLD were found. In addition, compared with participants in Q1, the prevalence of liver fibrosis increased by 45% in Q4 of TFQIFT3 (OR 1.45, 95% CI (1.03, 2.06)) (P < 0.05) in participants with MAFLD. Conclusions Impaired central sensitivity to FT3 was associated with MAFLD and its progression to liver fibrosis. More prospective and mechanism studies were warranted to confirm the conclusions.

Association Between Sensitivity to Thyroid Hormones and Metabolic Dysfunction-Associated Fatty Liver Disease in Euthyroid Subjects: A Cross-Sectional Study

“…The morbidity of MAFLD raised with increasing TFQI FT3 and FT3/FT4 levels when multiple potential confounders were adjusted. From the further analysis, subjects in the highest quartile of TFQI FT3 and FT3/FT4 had the notably highest MAFLD risk compared to the three lower quartile groups, which conformed to the findings of Wan et al 32 The research carried out by Lai et al 25 also expressed that TFQI FT3 and FT3/FT4 were closely associated with abnormal blood lipid as well as hepatic steatosis in populations with euthyroidism. This result further provided feasibility for preventing the progression of MAFLD by altering thyroid sensitivity.…”

Vitamin D Deficiency Is Associated with Impaired Sensitivity to Thyroid Hormones in Euthyroid Adults

“…Another study confirmed that TFQI was the indicator of resistance to thyroid hormones and was associated with diabetes and hypertension in euthyroid Tehranian populations [41]. Recently, emerging studies investigated the relationship between sensitivity to thyroid hormones, metabolic disorders, and non-alcoholic fatty liver disease in Chinese subjects [18][19][20]42]. However, the influencing factors of thyroid hormone sensitivity is unclear.…”

“…Subsequently, Teng et al demonstrated that impaired sensitivity to thyroid hormones was related to higher risks of cardiovascular disease and hyperuricemia and a lower risk of obesity in patients with subclinical hypothyroidism [18]. Recently, the association of impaired sensitivity to thyroid hormones with high levels of homocysteine [17], components of metabolic syndrome [19], and non-alcoholic fatty liver disease [20] were also revealed. However, the influencing factors of sensitivity to thyroid hormones and whether vitamin D deficiency is correlated with reduced sensitivity to thyroid hormones are unknown.…”

Association of sensitivity to thyroid hormones with all-cause mortality in euthyroid US adults: a nationwide cohort study

“…Education level was classified into high school education or lower, or education beyond high school ( 31 ). Smoking was classified as current smokers (those who have smoked ≥100 cigarettes and smoke currently), ex-smokers (who have smoked ≥100 cigarettes but do not smoke currently), and nonsmokers ( 24 ). Alcohol consumption was reported as standard drinks and converted to grams by multiplying by 14.…”

“…Central resistance phenomena affect the feedback loop set point within the central nervous system, while peripheral resistance phenomena diminish the metabolic effects of hormones ( 20 ). Impaired thyroid sensitivity was associated with metabolic disorders, including osteoporosis ( 22 ), carotid plaque ( 23 ), and metabolic dysfunction-associated fatty liver disease ( 24 ). A study has indicated that elevated levels of resistance to thyroid hormone indices are associated with diabetes-related mortality in the general population of the United States ( 20 ).…”