Thyroid Research Thyroid Research Archive Nodular Goiter

Thyroid nodules enlarge with time (II)

(March 2003)

The background of the study. There have been few long-term studies of patients with benign thyroid nodules, in particular studies in which changes in nodule volume were evaluated as a function of the cystic content of the nodule. In this study patients with benign thyroid nodules were reevaluated months to years after the first evaluation and biopsy.

How the study was done. The study subjects were 700 patients who had 854 biopsy-proven benign thyroid nodules 1 cm or larger in diameter when first evaluated. The patients were asked to return in 9 to 12 months for repeat ultrasonography and possible biopsy. Among them, 268 patients (38 percent), who had 330 nodules (39 percent), returned an average of 20 months later. The ultrasound images at both times were compared; nodules were considered to have enlarged if the maximal diameter had increased by >50 percent or by ≥3 mm, or if the volume had increased by ≥15 percent; the latter was the primary end point of the study.

The results of the study. As measured by a ≥15 percent increase in nodule volume, 129 nodules (39 percent) had enlarged. In contrast, based on a >50 percent increase in maximal diameter, 14 nodules (4 percent) enlarged, and based on a ≥3 mm increase in diameter, 86 nodules (26 percent) had enlarged. Nodules that were >50 percent cystic when first examined were less likely to enlarge than those with lesser cystic content. The likelihood of enlargement was not related to age, sex, initial serum thyrotropin concentration, or thyroxine therapy, but was related to duration between studies. The calculated time to a ≥15 percent increase in nodule volume in half the patients was 35 months; the proportion of patients having this increase in volume was 53 percent at three years and 89 percent at five years.

Sixty-one of the 268 patients (23 percent) had a second biopsy. The volume of these nodules had increased by an average of 69 percent, as compared with a 14 percent increase in nodules not biopsied again.

The conclusions of the study. Benign thyroid nodules, especially mostly solid nodules, grow slowly.

The original article. Alexander EK, Hurwitz S, Heering JP, Benson CB, Frates MC, Doubilet PM, Cibas ES, Larsen PR, Marqusee E. Natural history of benign solid and cystic thyroid nodules. Ann Intern Med 2003;138:315-8.