Low-Normal Thyroid Function Is Associated With Advanced Fibrosis Among Adults in the United States

Kim, Dong‐Hee; Yoo, Eric R.; Li, Andrew A.; Fernandes, Christopher T; Tighe, Sean; Cholankeril, George; Hameed, Bilal

doi:10.1016/j.cgh.2018.11.024

Cited by 44 publications

(41 citation statements)

References 8 publications

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“…In a systematic review by Mantovani et al, NAFLD was present in 50%–75% of T2DM patients, with variation according to ethnicity [ 14 ]. A number of researchers have explored risk factors associated with relevant hypothyroidism (serum TSH concentration within the upper normal range) and NAFLD [ 15 ]. Both T2DM and impaired thyroid function can increase the risk of existing NAFLD progressing to NASH, as well as the subsequent development of cirrhosis [ 16 ].…”

Section: Discussionmentioning

confidence: 99%

Association between Thyroid Function and Nonalcoholic Fatty Liver Disease in Euthyroid Type 2 Diabetes Patients

Huang

Yang

2020

Journal of Diabetes Research

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Thyroid function and type 2 diabetes mellitus (T2DM) are both associated with increased risks of adverse clinical outcomes in nonalcoholic fatty liver disease (NAFLD). Our study is aimed at evaluating the association between thyroid function and NAFLD in T2DM patients with normal thyroid function (euthyroid) and analyzing the potential effects of metformin on the pathological process. Overall, 369 T2DM patients were enrolled between July 2017 and September 2018 and stratified into NAFLD and non-NAFLD groups. Data on age, gender, body mass index (BMI, kg/m2), metformin use, and basal metabolic rate (BMR) were obtained from participants’ records. All patients were tested for biochemical markers, indexes of glucose metabolism, lipid metabolism, bone metabolism, and thyroid function at baseline. Multivariate analyses detected increased odds of NAFLD among individuals with T2DM per unit increase in their BMI and free triiodothyronine (FT3) and thyroid stimulating hormone (TSH); the odds ratios (OR) were 1.25, 3.02, and 1.58, respectively (all p<0.05). Positive correlations were detected between alanine aminotransferase (ALT) and FT3 (r=0.221, p=0.010), and negative correlations were noted between TSH and BMR (r=−0.618, p<0.001) and between BMR and FT3 (r=−0.452, p<0.001) in T2DM subjects with NAFLD. A significant difference in serum FT3 (t=2.468, p=0.0167) and TSH (t=2.658, p=0.010) levels was found between obese individuals with NAFLD who used and did not use metformin. The pathological mechanism of T2DM complicated by NAFLD in euthyroid patients may be associated with insulin resistance and a thyroid hormone resistance-like manifestation, i.e., relevant hypothyroidism. Metformin can potentially decrease the double-resistance situation, especially in obese individuals.

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Section: Discussionmentioning

confidence: 99%

Association between Thyroid Function and Nonalcoholic Fatty Liver Disease in Euthyroid Type 2 Diabetes Patients

Huang

Yang

2020

Journal of Diabetes Research

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“…The prevalence of advanced fibrosis was significantly higher in subjects with low-normal thyroid function and subclinical hypothyroidism than those with strict-normal thy-roid function. 86 In this study, multivariate analysis showed that "low-normal" thyroid function and subclinical hypothyroidism were significantly associated with a 1.9-fold increase (OR, 1.94; 95% CI, 1.10 to 3.44) and 2.1-fold increase (OR, 2.05; 95% CI, 1.01 to 4.16) in the risk for advanced fibrosis, respectively (p for trend=0.005). 86 A recent study hypothesized that thyroid hormone receptor may activate hepatic stellate cells, suggesting the potential role of thyroid hormone signaling in hepatic fibrogenesis.…”

Section: Hypothyroidismmentioning

confidence: 56%

“…86 In this study, multivariate analysis showed that "low-normal" thyroid function and subclinical hypothyroidism were significantly associated with a 1.9-fold increase (OR, 1.94; 95% CI, 1.10 to 3.44) and 2.1-fold increase (OR, 2.05; 95% CI, 1.01 to 4.16) in the risk for advanced fibrosis, respectively (p for trend=0.005). 86 A recent study hypothesized that thyroid hormone receptor may activate hepatic stellate cells, suggesting the potential role of thyroid hormone signaling in hepatic fibrogenesis. 87 Currently, an orally administered, small-molecule liver-directed thyroid hormone receptor b agonist (MGL-3196) is under development for the treatment of NASH and hyperlipidemia.…”

Section: Hypothyroidismmentioning

confidence: 56%

Extrahepatic Manifestations of Nonalcoholic Fatty Liver Disease

Kim

2020

Gut and Liver

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Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease and encompasses a spectrum of pathology from simple steatosis to inflammation and significant fibrosis that leads to cirrhosis. NAFLD and its comorbid conditions extend well beyond the liver. It is a multisystemic clinical disease entity with extrahepatic manifestations such as cardiovascular disease, type 2 diabetes, chronic kidney disease, hypothyroidism, polycystic ovarian syndrome, and psoriasis. Indeed, the most common causes of mortality in subjects with NAFLD are cardiovascular disease, followed by malignancies and then liver-related complications as a distant third. This review focuses on several of the key extrahepatic manifestations of NAFLD and areas for future investigation. Clinicians should learn to screen and initiate treatment for these extrahepatic manifestations in a prompt and timely fashion before they progress to end-organ damage.

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“…These studies together suggest an alternative option for diagnosis strategy of NAFLD in clinic, as liver biopsy is actually a traumatic examination that limits its clinical application although it is considered to be the "gold standard" of the diagnosing of NAFLD.It is clear that thyroid hormone is involved in human lipid metabolism, induces lipolysis in the liver and participates in the storage and degradation of lipid droplets in liver lysosome [17].When the thyroid function is low, the liver's lipase activity and triglyceride elimination is reduced, resulting in intrahepatic triglyceride accumulation and thereby promoting the development of NAFLD. In addition, low thyroid hormone level also affects the adipocytokines in the circulating system, such as tumor necrosis factor-alpha, leptin, adiponectin, etc [18].Adipocytokines promote the formation of hepatitis and liver brosis by direct hepatotoxicity or by promoting the formation of free radical [19].The correlation between thyroid hormones and liver brosis has been veri ed in clinic by previous studies [11,15,[20][21][22]. Liu etal[21] discussed the results of 1773 health examinations.…”

Section: Discussionmentioning

confidence: 99%

Correlation Between the Thyroid Hormone Levels and Nonalcoholic Fatty Liver Disease in Type 2 Diabetic Patients with Normal Thyroid Function

Zhang¹,

Liu²,

Li³

et al. 2020

Preprint

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Background: The objective of this study is to retrospectively analyze the correlation between the thyroid hormones and nonalcoholic fatty liver disease (NAFLD) in type 2 diabetes mellitus (T2DM) patients with normal thyroid function. Methods: Totally 586 T2DM patients with normal thyroid function participated in this research and were divided into T2DM without NAFLD (240 cases) group and T2DM with NAFLD (346 cases) group. The NAFLD fibrosis score (NFS) >0.676 was defined as progressive liver fibrosis and used to categorize the patients into T2DM without progressive liver fibrosis group (493 cases) and T2DM with progressive liver fibrosis group (93 cases). Results: The results indicated that the levels of free triiodothyronine (FT3) and total triiodomethylamine (TT3) were significantly higher while the free thyroxine (FT4) level was lower in T2DM with NAFLD group than that in T2DM2 without NAFLD group (p<0.05). The levels of FT3, FT4 and TT3 in patients with progressive liver fibrosis were significantly lower in patients with progressive liver fibrosis than that in patients without progressive liver fibrosis (p<0.05). Logistic regression analysis showed a negative relationship between FT4 level and NAFLD (p=0.026), between the levels of FT4,TT3 and total thyroxine (TT4) and the risk of progressive hepatic fibrosis (p=0.022, p=0.007,p=0.046).Conclusion: There is a certain correlation between thyroid hormone levels and NAFLD in T2DM patients, suggesting that the assessment of thyroid hormone levels in T2DM patients with normal thyroid function is of great significance in the prevention and treatment of NAFLD.

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Low-Normal Thyroid Function Is Associated With Advanced Fibrosis Among Adults in the United States

Cited by 44 publications

References 8 publications

Association between Thyroid Function and Nonalcoholic Fatty Liver Disease in Euthyroid Type 2 Diabetes Patients

Association between Thyroid Function and Nonalcoholic Fatty Liver Disease in Euthyroid Type 2 Diabetes Patients

Extrahepatic Manifestations of Nonalcoholic Fatty Liver Disease

Correlation Between the Thyroid Hormone Levels and Nonalcoholic Fatty Liver Disease in Type 2 Diabetic Patients with Normal Thyroid Function

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