ASSOCIATION OF SUBCLINICAL HYPOTHYROIDISM WITH THYROID NODULES AND RISK OF MALIGNANCY: A RETROSPECTIVE OBSERVATIONAL STUDY

Abstract

Background: Thyroid nodules are among the most common endocrine disorders encountered in clinical practice, with a prevalence increasing with age and the widespread use of high-resolution ultrasonography. Although the majority of thyroid nodules are benign, approximately 5–15% harbor malignancy. Serum thyroid-stimulating hormone (TSH) has emerged as a potential biomarker associated with thyroid carcinogenesis. Subclinical hypothyroidism (SCH), characterized by elevated serum TSH with normal free thyroxine (FT4) levels, has been proposed as a possible risk factor for thyroid cancer due to the trophic effects of TSH on thyroid follicular cells. However, the relationship between SCH and thyroid malignancy remains controversial. Aim: To evaluate the association between subclinical hypothyroidism and thyroid nodules and to determine whether SCH is associated with an increased risk of thyroid malignancy. Methods: A retrospective observational study was conducted using  100 adult patients with thyroid nodules managed between March 2022 and April 2026. Patients were categorized into euthyroid and subclinical hypothyroid groups based on thyroid function tests. Clinical characteristics, ultrasonographic findings, Bethesda cytology, operative details, and final histopathology were analyzed. Categorical variables were compared using the Chi-square test, continuous variables using Student's t-test or Mann–Whitney U test, and multivariable logistic regression was performed to identify independent predictors of malignancy. Statistical significance was defined as p < 0.05. Results: Among the 100 patients, 72 were euthyroid and 28 had subclinical hypothyroidism. Thyroid malignancy was identified in 26 patients, with a higher proportion observed in the SCH group compared with the euthyroid group. Patients with SCH demonstrated higher mean serum TSH levels, increased frequency of TI-RADS 4–5 lesions, and higher Bethesda V/VI cytology categories. Multivariable logistic regression identified subclinical hypothyroidism, higher TSH levels, TI-RADS 5 classification, and Bethesda V/VI cytology as independent predictors of thyroid malignancy. ROC analysis demonstrated good discriminatory ability of serum TSH for predicting malignancy. Conclusion: In this cohort, subclinical hypothyroidism was associated with an increased likelihood of thyroid malignancy among patients with thyroid nodules. Elevated serum TSH may serve as an adjunctive marker for risk stratification when interpreted alongside ultrasonographic and cytological findings. Prospective multicenter studies are warranted to validate these observations.