Non-Alcoholic Fatty Liver Disease (NAFLD) is currently recognized as the most common chronic liver disorder worldwide, with a prevalence ranging from 25% to 30% in the general population (1). It encompasses a spectrum of hepatic conditions, from simple steatosis to non-alcoholic steatohepatitis (NASH), which can progress to fibrosis, cirrhosis, and even hepatocellular carcinoma (2). NAFLD is strongly associated with metabolic syndrome components such as obesity, type 2 diabetes mellitus, dyslipidemia, and insulin resistance (3).

Hypothyroidism, characterized by decreased levels of thyroid hormones, has emerged as a potential but often under-recognized risk factor for NAFLD. Thyroid hormones play a significant role in lipid metabolism, glucose regulation, and energy expenditure, all of which are closely related to hepatic fat accumulation (4). In hypothyroid states, reduced basal metabolic rate, alterations in lipid profile, and insulin resistance contribute to the development of fatty infiltration in the liver (5).

Recent studies have suggested a positive correlation between hypothyroidism and increased prevalence of NAFLD, particularly in patients with subclinical hypothyroidism and overt hypothyroidism (6). However, there is limited data from Indian populations, and particularly from tertiary care settings, regarding the exact burden of NAFLD among hypothyroid individuals and the associated metabolic risk factors.

This study aims to estimate the prevalence of NAFLD among patients diagnosed with hypothyroidism and to identify key risk factors contributing to its development in a tertiary care hospital. Early recognition of this association could aid in timely interventions and reduce the progression to more severe liver diseases.

A total of 150 adult patients who visited Travancore Medical College Hospital, Travancore Medicity, Kerala, aged between 18 and 65 years, diagnosed with primary hypothyroidism (based on elevated serum thyroid-stimulating hormone [TSH] and low free T4 levels), were included. Patients were either newly diagnosed or on levothyroxine therapy.

Inclusion Criteria:

• Adults aged 18–65 years
• Confirmed diagnosis of primary hypothyroidism
• Willingness to participate and provide informed consent

Exclusion Criteria:

• History of alcohol intake >20 g/day for men and >10 g/day for women
• Presence of viral hepatitis, autoimmune liver disease, or other known liver disorders
• Pregnant or lactating women
• Patients on medications known to cause hepatic steatosis (e.g., corticosteroids, tamoxifen)

Data Collection:

A detailed clinical history and physical examination were recorded. Anthropometric measurements including height, weight, and body mass index (BMI) were obtained. Fasting blood samples were collected for the following investigations:

• Thyroid profile (TSH, Free T3, Free T4)
• Liver function tests (ALT, AST)
• Lipid profile (total cholesterol, LDL, HDL, triglycerides)
• Fasting blood glucose

Diagnosis of NAFLD:

NAFLD was diagnosed based on ultrasonographic evidence of hepatic steatosis (diffuse increase in echogenicity of the liver compared to the renal cortex) in the absence of alcohol intake or other known causes of liver disease. Abdominal ultrasound was performed using a high-resolution B-mode scanner by an experienced radiologist blinded to the clinical details.

Statistical Analysis:

All data were entered into Microsoft Excel and analyzed using SPSS software version 25.0. Descriptive statistics were used to express continuous variables as mean ± standard deviation and categorical variables as frequency and percentage. The chi-square test was used for categorical variables, and the Student’s t-test was applied to compare means. Logistic regression analysis was performed to identify independent risk factors for NAFLD. A p-value <0.05 was considered statistically significant.

A total of 150 patients with primary hypothyroidism were included in the study, with a mean age of 41.6 ± 10.2 years. The majority were females (n = 112; 74.7%) and 38 were males (25.3%). Out of the total population, 68 patients (45.3%) were diagnosed with NAFLD based on ultrasound findings.

Table 1: Baseline Characteristics of Study Population

(p<0.05 considered statistically significant)

(Table 1 shows that higher BMI, ALT, and triglyceride levels were significantly associated with NAFLD.)

Table 2: Logistic Regression Analysis of Risk Factors for NAFLD

**(Table 2 shows multivariate logistic regression where BMI, triglycerides, and ALT were significant independent predictors of NAFLD.)

In summary, the prevalence of NAFLD among hypothyroid patients was 45.3%. BMI, serum triglycerides, and elevated ALT levels were significantly higher among NAFLD patients compared to those without hepatic steatosis (Table 1). Logistic regression analysis identified BMI >25 kg/m² (OR = 2.6), triglycerides >150 mg/dL (OR = 1.9), and ALT >40 U/L (OR = 1.7) as independent risk factors (Table 2).

This study evaluated the prevalence and associated risk factors of Non-Alcoholic Fatty Liver Disease (NAFLD) in patients with hypothyroidism and found that 45.3% of the hypothyroid individuals had sonographic evidence of hepatic steatosis. This aligns with previous research indicating a high prevalence of NAFLD among patients with thyroid dysfunction, particularly those with subclinical or overt hypothyroidism (1,2).

The pathophysiological link between hypothyroidism and NAFLD involves multiple metabolic pathways. Thyroid hormones regulate lipid metabolism, hepatic gluconeogenesis, insulin sensitivity, and mitochondrial activity in hepatocytes (3). In hypothyroidism, reduced basal metabolic rate and dyslipidemia—characterized by elevated triglycerides and LDL cholesterol—promote hepatic fat accumulation (4,5). In our study, patients with NAFLD showed significantly higher serum triglyceride levels and BMI compared to those without NAFLD, suggesting a strong metabolic contribution.

Obesity, particularly central adiposity, is a well-established risk factor for NAFLD (6). In our cohort, individuals with BMI >25 kg/m² had significantly increased odds of developing NAFLD. This is consistent with earlier studies which have shown that overweight and obese individuals, especially in the presence of insulin resistance, are at greater risk for hepatic steatosis (7,8). Additionally, elevated alanine aminotransferase (ALT) levels, found significantly more in the NAFLD group, further support hepatic involvement, even in the absence of clinical symptoms (9).

The association between thyroid dysfunction and NAFLD may also be mediated by altered adipocytokine levels and systemic inflammation. Low thyroid function leads to increased leptin and decreased adiponectin levels, which are known contributors to hepatic fat deposition and fibrosis (10,11). Recent meta-analyses have confirmed the positive correlation between higher thyroid-stimulating hormone (TSH) levels and NAFLD, independent of other metabolic factors (12,13). However, in our study, TSH levels were not significantly different between NAFLD and non-NAFLD groups, suggesting that other metabolic components may be more influential.

Furthermore, insulin resistance, which often coexists with hypothyroidism, plays a central role in the pathogenesis of NAFLD. Although we did not directly assess insulin resistance using HOMA-IR, elevated fasting glucose levels and triglycerides in NAFLD patients indirectly reflect underlying insulin resistance (14). These findings support previous observations that hypothyroidism can exacerbate insulin resistance and dysregulate lipid metabolism, thereby increasing susceptibility to NAFLD (15).

Gender distribution in our study revealed a female predominance in both groups, which is reflective of the higher prevalence of hypothyroidism among women in general (6). However, no significant gender-based difference in NAFLD prevalence was noted, indicating that metabolic factors may override gender influence in this specific population (7).

Given the silent progression of NAFLD, early screening among high-risk groups such as hypothyroid patients is vital. Ultrasonography remains a cost-effective and widely available tool for the detection of hepatic steatosis, although it lacks sensitivity in early-stage disease or in patients with a BMI <25 kg/m² (8).

Limitations of this study include its cross-sectional design, which precludes causal inference, and the lack of liver biopsy confirmation, the gold standard for NAFLD diagnosis. In addition, data on lifestyle factors such as diet, physical activity, and smoking status were not evaluated, which may also influence hepatic fat accumulation (9). Future studies with larger sample sizes and longitudinal follow-up are needed to better understand the causal relationship and the impact of thyroid hormone replacement on NAFLD outcomes (10).

In conclusion, our findings highlight a high prevalence of NAFLD among hypothyroid patients and suggest that obesity, hypertriglyceridemia, and elevated liver enzymes are important risk indicators. Early detection and management of NAFLD in this population can potentially prevent progression to more severe liver diseases.

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