Editor's Note: A recent study led by Dr. Vidhu V. Thaker from Columbia University Medical Center has revealed a significant association between subclinical hypothyroidism and metabolic-associated steatotic liver disease (MASLD) in adolescents. This research provides new insights into the complex relationship between these two conditions and was published online in Hepatology, a leading journal in the field of hepatology.Subclinical hypothyroidism, previously referred to as mild thyroid dysfunction or impaired thyroid reserve, is increasingly detected due to advancements in thyroid function testing. Research has shown that subclinical hypothyroidism is linked to various health conditions, including coronary heart disease, diabetes, hypertension, ischemic stroke, metabolic syndrome, and more.
In recent years, numerous studies have demonstrated a significant association between subclinical hypothyroidism and MASLD in adults. Systematic reviews and meta-analyses have found that adults with subclinical hypothyroidism have a significantly higher risk of developing MASLD compared to the general population. For example, a meta-analysis published in Gut evaluated observational studies and revealed an increased risk of MASLD in patients with primary hypothyroidism, including those with subclinical hypothyroidism. Another study comparing the risk of metabolic syndrome and its components between individuals with subclinical hypothyroidism and those with normal thyroid function found that the risk of metabolic syndrome increased by 28% in individuals with subclinical hypothyroidism, particularly due to central obesity, hypertension, elevated triglyceride levels, and reduced HDL cholesterol levels.
While the link between subclinical hypothyroidism and MASLD in adults has been extensively studied, research on adolescents remains scarce. To address this gap, Professor Vidhu V. Thaker and her team conducted a study to evaluate the relationship between thyroid-stimulating hormone (TSH) levels and MASLD histopathological characteristics in adolescents.
Study Overview:
This observational study utilized liver biopsy and clinical data prospectively collected from the Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN). The researchers compared thyroid function test results in adolescents with MASLD to age-matched healthy controls (≤18 years) from the National Health and Nutrition Examination Survey (NHANES). To ensure accuracy, individuals with overt hypothyroidism, abnormal thyroid antibodies, or those on thyroid medications were excluded. Subclinical hypothyroidism was defined as TSH levels between 4.5 and 10.0 mIU/L.
Key Findings:
The study found that adolescents with MASLD in the NASH CRN cohort (n=218, with 421 observations) had significantly higher average TSH, total thyroxine (T4), total triiodothyronine (T3), and free T4 levels compared to healthy controls from the NHANES cohort (n=2,198) (P<0.001). Further analysis indicated a positive correlation between TSH levels and the severity of hepatic steatosis over time (P=0.03). Additionally, subclinical hypothyroidism at baseline was associated with borderline or definitive metabolic-associated steatohepatitis (MASH) (P=0.03) and linked to changes in liver fibrosis (P=0.01).
Researcher’s Insights:
Professor Vidhu V. Thaker: “This study shows that even within the normal range of thyroid hormone levels, elevated TSH is independently associated with greater severity of hepatic steatosis in MASLD. It suggests that subclinical hypothyroidism could be an independent risk factor for MASLD, warranting increased attention from clinicians. This finding provides new clues about the potential role of TSH in the development and progression of MASLD, which could inform future prevention and treatment strategies for adolescents with MASLD. Clinicians should closely monitor thyroid function in patients at risk of MASLD, especially those with hypothyroidism, and take early intervention measures when necessary.”
Despite the established link between subclinical hypothyroidism and MASLD, the underlying mechanisms remain unclear and require further investigation. Future studies should focus on the specific pathways through which TSH contributes to MASLD and explore potential therapeutic strategies for modulating TSH levels. Additionally, larger and longer-term follow-up studies are needed to establish a causal relationship between subclinical hypothyroidism and MASLD, providing more robust evidence for clinical management.
