Ultrasound of Benign Thyroid Nodules: A 120 Months Follow-Up Study

Carlo Cappelli; Ilenia Pirola; Elena Gandossi; Mario Rotondi; Claudio Casella; Davide Lombardi; Barbara Agosti; Alberto Ferlin; Maurizio Castellano


Clin Endocrinol. 2021;94(5):866-871. 

In This Article


From January 2007 to March 2009, 1248 patients underwent thyroid fine-needle aspiration cytology in our Department. Among them, 966 (77.4%) patients were given a cytological diagnosis of benign nodule. During follow-up, 289 patients were lost, meaning that the total number of patients analysed was 677 (474 women and 203 men), with a mean age of 45.6 (16–71) years. Among them, 474 patients had a single nodule; 410 subjects showed a solid nodule whereas 267 a mixed one. Among all the patients, 657 (97%) subjects were born and live in northern Italy.

In 559 of the 677 patients (82.7%), the size of the nodule remained stable during follow-up; 42 (6.2%) patients experienced spontaneous nodule shrinkage, and 75 (11.1%) patients showed nodule growth. All of these nodules that increased in size were re-submitted to FNA: in 3/75 (4%) patients, cytology revealed a differentiated thyroid cancer.

The baseline features of the study population are reported in Table 1.

Patients with or without nodule growth during follow-up were superimposable at baseline for age, gender, TSH values, number of patients on levothyroxine treatment and nodule characteristics.

Among the nodules with volume increase, the mean change in largest diameter was 2 mm, from 28.9 ± 8.5 to 31.1 ± 7.7 mm (P < .001), whereas the mean change in those that shrank was 1 mm, from 28.8 ± 7.7 to 27.9 ± 8.0 mm (P < .001) after 10 years of follow-up. Changes in nodule size occurred in a linear fashion, starting from the first year of observation (Figure 1). Of the 117 patients who showed a change in nodule volume (both shrinkage and growth) at the end of the study, for 171 patients (83%) it occurred within the first five years follow-up. In details, 59/75 (79%) and 41/42 (98%) patients showed nodular volume growth or shrinkage within the first five 5 years, respectively. The maximum diameter increased in 37/75 (49%) and decreased in 28/45 (62%) patients in the same period.

Figure 1.

Estimated mean with 95% CLs of the largest diameter and volume of nodule during follow-up in patients that show nodular grew and shrank, annually evaluated by ultrasound

In addition, nodules were stratified in accordance with their maximum diameter at the time of recruiting (D-type1 up to 19 mm, D-type 2 from 20 to 29 mm, D-type 3 from 30 to 39 mm and D-type 4 40 mm or more), and volume (V-type 1 up to 1.99 ml, V-type 2 from 20 to 20.99 ml, V-type 3 from 30 to 30.99 ml and V-type 4 40 ml or more).

Seventeen percent of nodules were D-type 1, 44% and 31% D-type 2 and D-type 3, respectively, and 8% were D-type 4; V-type 1 were found in 46% of patients, 15% were V-type 2, 31% were V-Type 3 and 8% were V-type 4.

The percentage of nodules that underwent growth was superimposable among both quartiles of maximum diameter (12.9% in D-type 1, 13.4% D-type 2, 14.2% D-type 3 and 15.9% D-type 4) and quartiles of volume (13.6% in V-type 1, 15.8% V-type 2, 15.4% V-type 3 and 16.8% V-type 4) (P = .864 and P = .903, respectively).

All baseline variables in predicting nodular growth were entered to an adjusted multivariate logistic regression model (Table 2). None of the parameters taken into account was associated with nodular growth.