In an article published by Nou et al1 in the Journal of Clinical Endocrinology & Metabolism, researchers addressed the important clinical issue of the optimal or appropriate time interval to monitor thyroid nodules after an initial fine needle aspiration (FNA) was found to be benign.

For the study, the authors identified 1,369 patients with 2,010 benign thyroid nodules by FNA from their institution who had a thyroid nodule larger than 1 cm ultrasonically and also had normal or elevated serum thyroid-stimulating hormone (TSH).

Charts were reviewed from the selected patients using available data (e.g., clinical, laboratory, surgical pathology and thyroid ultrasounds) to determine the fate of the nodules and the patients. The study cohort was composed of 89.9% women; mean age was 50 years, and the average nodule size was 2.4 cm.

The patients were followed for a mean of 8.5 years (range, 0.25 to 18.1 years), and 44% were monitored for 10 years or more. Of these patients, 24% (325 of 1,369) had a thyroidectomy while the remaining 76% (n=1,014) were analyzed by their last clinical appointment.

Interestingly, 1.3% (n=18) of patients had a false negative FNA defined by pathologic examination, and the majority were papillary thyroid cancer (89%; n=16).

There were no thyroid-related deaths.1

An important part of the study relates to the frequency of thyroid ultrasounds relative to a subsequent thyroidectomy that demonstrated thyroid cancer.1 If the next ultrasound follow-up was less than 2 years, 7.5% of patients had a false negative FNA; at less than 3 years, the false negative rate was 6.6%, and at less than 4 years, 8.2%. Using FNA as the determination of malignancy, 7.4%, 6.6% and 4.5% of patients at 2, 3 and 4 years, respectively, had false negative results. These differences are not statistically significantly different.

Based on these findings (i.e., low disease-related mortality and lack of mortality despite false negative rates), the authors conclude that “these data support a recommendation for repeat thyroid nodule evaluation 2–4 years after the initial benign FNA.”1

Questions Remain

This article by Nou et al represents an important contribution to the clinical practice of medicine and endocrinology. It gives reasonable guidance for the frequency of follow-up visits, such as thyroid ultrasounds, in patients with a benign thyroid nodule.

However, there are several issues that should be noted. This is a retrospective study with its inherent problems. There was no systematic evaluation of thyroid nodules at a predefined interval, and we are not certain that thyroid nodule area, as compared with two dimensions alone, was compared in each patient. The cytopathologists are obviously experienced, and the ability to extrapolate these results to other institutions may be problematic.