Thyroid nodules develop in nearly 50 percent of adults and become more prevalent with age. For thyroid nodules that are at least 1 cm in diameter, appropriate evaluation includes a thyroid-stimulating hormone (TSH) assay and a fine-needle aspiration (FNA). The majority of FNA results are benign, and recommended follow-up consists of periodic clinical examinations or ultrasonography, with optional use of suppressive L-thyroxine therapy. If a nodule increases in size, recommendations generally include repeat FNA or surgery because of the possibility of malignancy. Alexander and associates examined the natural history of benign thyroid nodules in a retrospective study of patients who underwent initial ultrasonography and FNA and returned for follow-up ultrasonography within a five-year period.

The authors reviewed the records of patients referred to the thyroid nodule clinic at Brigham and Women's Hospital, Boston, between 1995 and 2000. The study sample included 268 patients who had FNA-benign thyroid nodules on initial examination (330 benign nodules with maximal diameter of 1 cm or greater) and underwent follow-up ultrasonography within one month to five years.

The change in nodule size from initial examination to follow-up examination was assessed using three criteria: (1) change in maximal diameter greater than 50 percent; (2) change in maximal diameter of 3 mm or more; and (3) change in calculated volume of 15 percent or more. Maximal diameter increased by more than 50 percent in 14 nodules (4 percent) and by 3 mm or greater in 86 nodules (26 percent); calculated volume increased by 15 percent or more in 129 nodules (39 percent).

Cystic nodules were less likely to grow than were those with a greater solid component. Nodule growth correlated significantly with the interval between initial ultrasonography and follow-up examination, but not with the patient's age, sex, baseline serum TSH concentration, orl-thyroxine use. At the time of the second ultrasonography, repeat ultrasonography was performed on 74 nodules (61 patients) because of nodule growth. The FNA findings were benign for all except one nodule, which was determined to be a poorly differentiated papillary carcinoma.

The authors conclude that although many benign thyroid nodules grow slowly over time, this growth does not represent a false-negative initial FNA or an increased likelihood of malignant transformation.