A Prospective Study on Challenges in the Management of Indeterminate Thyroid Nodules Without Molecular Testing

Treating indeterminate thyroid nodules (ITNs) without validated molecular testing (MT) has been challenging. However, adding specific clinical and radiological parameters helps us to decide on treatment for a few individuals. The risk of malignancy in ITN after eliminating the obvious risk parameters needs to be studied.

This prospective single-centre analysis included patients who underwent fine needle aspiration cytology (FNAC) of thyroid between March 2022 and October 2023. The study included patients with thyroid nodules classified as Bethesda III/IV who subsequently underwent surgery. Different clinicopathological and FNAC-related parameters were statistically analysed to predict malignancy, after excluding those factors that would strongly suggest malignancy.

Among 1501 patients who underwent FNAC, 207 met the inclusion criteria. The mean age of the study population was 39 ± 12.1 years, and the majority were women (80.2%). Among the ITNs, 86% were Bethesda III, and 14% were Bethesda IV nodules. The risk of malignancy in Bethesda III and IV nodules was 67.4% and 69%, respectively. On multivariate analysis, it was noted that hypothyroidism was the single independent factor that predicted malignancy associated with a significant odds of 0.309 (95%CI:0.127-0.784, p = 0.013). The most common malignancy among ITNs was the follicular variant of papillary thyroid carcinoma.

Women less than 40 years of age, in this cohort, had a higher risk of malignancy compared to the Western population. More than half of the patients diagnosed with ITN underwent surgery. Hypothyroidism is an independent factor that may predict the risk of malignancy in ITNs, and this needs external validation. Rule-in MT might be important in categorizing patients with ITN in the Indian population.