1. The majority of benign thyroid nodules did not significantly increase in size during a 5-year follow-up period.
2. While a minority of patients experienced new nodule growth, the diagnosis of thyroid cancer was rare.
Evidence Rating Level: 1 (Excellent)
Study Rundown: The increase in detection of asymptomatic thyroid nodules has paralleled the improvement in imaging techniques. Existing guidelines for cytologically benign or sonographically unsuspicious thyroid nodules recommends serial ultrasound exams to assess for significant growth, defined as ≥20% increase in ≥2 nodule diameters, with a minimum increase of 2 mm. If growth is observed, cytological assessment is warranted. However, the natural history of benign thyroid nodules, the likelihood of their growth and their malignant potential is not well elucidated.
This study aimed to gauge the natural history of benign thyroid nodules by follow-up. It was found that the majority of nodules were stable in size, with a minority experiencing significant growth and a subset experiencing shrinkage. Nodule growth was associated with multinodular disease, larger nodules at baseline and younger age. A very small minority of patients was diagnosed with thyroid cancer in the nodules being followed. The strengths of this study include its size and prospective design but it is limited by its predictive modeling. Iodine intake influences thyroid nodules. The study population was from Italy; therefore, the findings are difficult to generalize to other populations. Nevertheless, the findings support a revision to current guidelines to recommend an ultrasound exam performed 1 year and 5 years after detection of a benign thyroid nodule (given that no changes are noted). Closer follow-up can be considered in patients more likely to experience nodule growth.
In-Depth [prospective cohort]: This study prospectively enrolled 992 patients with 1 to 4 asymptomatic thyroid nodules, studying a total of 1,567 nodules at baseline. Patients were followed up with ultrasound exam yearly for 5 years. Sixty-nine percent of patients experienced stable size of their nodules, 18.5% (95%CI 16.4%-20.9%) experienced shrinkage of ≥1 nodules, and 15.4% (95%CI 14.3%-16.5%) experienced significant growth. Of the 1,567 nodules at baseline, 11.1% (95%CI 10.3%-11.9%) increased in size. Ninety-three patients (9.3%; 95%CI 8.4%-10.2%) developed new nodules. Thyroid cancer was diagnosed in 5 of the original nodules (0.3%; 95%CI 0.2%-0.4%). Statistical analysis revealed several factors associated with nodule growth, with older patients with multinodular disease and largest nodule size exceeding 7.5 mm having the highest chances of nodule growth during follow-up.
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