During 5 years of follow-up, cancer arose in only 0.3% of thyroid nodules that were cytologically and sonographically benign at baseline, according to a large prospective study published online March 3 in JAMA.

Furthermore, only two of the five nodules that became cancerous had grown beforehand, reported Dr. Cosimo Durante of the Sapienza University of Rome and his associates. “These data suggest that the American Thyroid Association’s recommendation for indication for repeat cytology should be revised. Clinical and sonographic findings should probably play larger roles in the decision-making process,” the researchers said (JAMA 2015;313:926-35). Advances in diagnostic imaging have increased the detection of thyroid nodules, the great majority of which are found to be benign. For such nodules, the ATA recommends repeating thyroid ultrasonography at 6-18 months and then every 3-5 years thereafter, as long as nodules do not significantly grow (defined as at least a 20% increase in two nodule diameters, with a minimum increase of at least 2 mm [Thyroid 2009;19:1167-214]). But little is known about rate, extent, or predictors of nodule growth, the researchers noted. Therefore, they performed annual thyroid ultrasound examinations on 992 patients who had one to four asymptomatic subcentimeter thyroid modules that were cytologically or sonographically benign at baseline.

After 5 years of follow-up, just 15.4% of patients had experienced significant nodule growth according to the ATA definition, the researchers reported. Average growth was 4.9 mm, and 9.3% of patients developed new nodules, of which one was found to be cancerous. Growth was least likely when a patient’s largest nodule measured 7.5 mm or less and was significantly more likely when patients had multiple nodules instead of one; had baseline nodule volume greater than 0.2 mL; were up to 45 years old, compared with at least 60 years of age; and were male, the investigators said.

Among older patients, having a body mass index of 28.6 kg/m2 more than doubled the odds of nodule growth, in keeping with recent reports linking obesity and insulin resistance with nodular thyroid disease, they added.

The findings suggest that repeat thyroid ultrasonography could be safely extended to 12 months for initial follow-up and to every 5 years thereafter for most patients, as long as nodule size remained stable, Dr. Durante and his associates said. “This approach should be suitable for about 85% of patients, whose risk of disease progression is low. Closer surveillance may be appropriate for nodules occurring in younger patients or older overweight individuals with multiple nodules, large nodules (greater than 7.5 mm), or both,” they added.

The Umberto Di Mario Foundation, Banca d’Italia, and the Italian Thyroid Cancer Observatory Foundation funded the study. The authors reported having no conflicts of interest.