Benign small nodules in the thyroid gland are common. Since the (mostly incidental) detection of such asymptomatic nodules has also increased in recent years, the question arises as to how to proceed in this case: Is it sufficient if the benignity has been confirmed by ultrasound and cytological examination, or should such nodules also be removed to be on the safe side? A study published in JAMA clearly favors the first option.
Currently, there is no clear consensus regarding the optimal follow-up of thyroid nodules that are sonographically unsuspicious or cytologically defined as benign. Guidelines recommend in this case regular ultrasound examinations and in case of strong growth a renewed cytological analysis. Is such an approach justifiable, or would it not be better to aim for complete surgical removal of the nodes in the sense of prevention?
Almost 1000 patients followed up
The prospective, multicenter, observational study from Rome included a total of 992 patients with one to four asymptomatic thyroid nodules. These had previously been classified as benign by sonography or cytology. Follow-up lasted five years and included “significant growth” of nodes (detected with annual ultrasounds) as the primary endpoint. Specifically, this meant an increase of ≥20% in at least two nodular diameters and a minimal growth of at least 2 mm. Secondary endpoints included the diagnosis of thyroid cancer during the follow-up period or the occurrence of new nodules.
In 184 persons, i.e. 18.5%, the nodes shrank spontaneously. In contrast, 153 patients showed significant nodal growth, which meant that 174 of the original 1567 nodules grew (11.1%) – with a maximum increase in diameter of 4.9 mm (from 13.2 to 18.1 mm). Growth was associated with the presence of multiple nodes: Risk increased by a factor of 2.2 with two nodes, 3.2 with three nodes, and 8.9 with four nodes. Other associated factors were male sex (OR 1.7; 95% CI 1.1-2.6) and nodal volume of more than 0.2 mL (OR 2.9; 95% CI 1.7-4.9). In people older than 60 years, the risk of growth was reduced by half (compared with those younger than 45 years).
The vast majority of nodes remain benign
Five nodules, only 0.3% of all cases, were eventually diagnosed with thyroid cancer during follow-up, indicating that with ultrasound and cytologic examination 99.7% of all nodules can be correctly classified as benign and therefore no preventive surgery is indicated. Four of the nodules had been considered suspicious on the initial ultrasound, but the subsequent tissue sample had been negative. Of the 93 new nodules that developed during follow-up, one was cancerous. Two of the five tumor nodules had grown significantly during the follow-up period. A previously invisible tumor was discovered by chance during a thyroidectomy.
The authors concluded that approximately 89% of asymptomatic nodules classified as benign by sonography or cytology showed no significant growth during five years, and only a fraction of these, less than 1%, developed into cancer. The results are relevant for the follow-up of such incidentally detected nodules. When ultrasound and cytologic examination can so accurately predict which nodes are benign, the consequences of precautionary surgical removal of the nodes outweigh the benefits. Of course, sonographic detection of suspected cases (e.g., low-echo nodules that are then examined cytologically) requires competent and expert use of ultrasound as a diagnostic tool. And sonography examinations should be performed not after five years, but again after one year, just to be on the safe side. After that, however, an interval of five years is sufficient.
Source: Durante C, et al: The Natural History of Benign Thyroid Nodules. JAMA 2015; 313(9): 926-935.
InFo ONCOLOGY & HEMATOLOGY 2015; 3(11-12): 5.
