Majority of Benign Thyroid Nodules Show No Change Over 5 Years

Nancy A Melville

March 03, 2015

The vast majority of asymptomatic, benign thyroid nodules show no significant growth over a 5-year follow-up, suggesting that existing guidelines on follow-up of such tumors can safely be relaxed, according to a new study.

Even among the five of 1567 original nodules that did become cancerous, only two had grown over the 5-year follow-up, the research, published in the March 3 issue of the Journal of the American Medical Association by Cosimo Durante, MD, PhD, of Universita di Roma Sapienza, Italy, and colleagues, indicates.

"Until now, nodule growth was regarded as a possible predictor of malignancy," senior author Sebastiano Filetti, MD, of the Universita di Roma Sapienza, told Medscape Medical News.

"This was not confirmed in our study: if a nodule is cytologically or sonographically benign, it is very likely that it will remain benign during follow-up, even if it grows," he said. "These nodules can thus be safely managed with more relaxed follow-up schedules than those currently recommended."

Advances in diagnostic imaging have led to a substantial increase in the detection of small thyroid nodules, but more than 90% of the nodules are clinically insignificant.

Initial fine-needle aspiration of the nodule is recommended only when there are suspicious features on ultrasound, but a lack of understanding on the natural history of thyroid nodules means that the appropriate course of subsequent clinical follow-up for those nodules can be challenging.

Asked to comment on this new paper, Megan Rist Haymart, MD, a specialist in endocrinology at the University of Michigan Health System in Ann Arbor, said the findings by Dr Durante et al are important to provide clinicians with evidence of long-term progress in a large number of thyroid nodules.

"Prior to this study, there were no great data on appropriate surveillance of thyroid nodules," she told Medscape Medical News.

"This study suggests that few nodules are missed cancers and that size change alone may not be the best criteria for repeat fine-needle aspiration, as only two of the five cancers diagnosed during follow-up grew."

Nevertheless, continued research is still needed to better understand the small but important cases that do become thyroid cancer, she noted. "This study is important to clinicians and patients, but since the number of patients with events is small (n = 5), additional studies are needed."

Number of Nodules and Volume Associated with Growth

To better evaluate the natural long-term course of nodules, Dr Durante and colleagues enrolled 992 patients with one to four asymptomatic, sonographically or cytologically benign thyroid nodules in the prospective, multicenter trial.

An analysis of annual thyroid ultrasound exams for the first 5 years of follow-up showed nodule growth among 153 of the patients (15.4%). Growth was defined according to American Thyroid Association standards as an increase of 20% or more in at least two nodule diameters, with a minimum increase of 2 mm.

Among 174 (11.1%) of 1567 original nodules, there was an increase in size, with a mean largest diameter increase over 5 years being 4.9 mm (95% CI, 4.2 – 5.5 mm).

Factors found to be most associated with nodule growth included the presence of multiple nodules (odds ratio [OR], 2.2 for two nodules; OR, 3.2 for three nodules; and OR, 8.9 for four nodules).

Main nodule volumes larger than 0.2 mL also were associated with growth (OR, 2.9 for volumes > 0.2 to < 1 mL; OR, 3.0 for volumes > 1 mL), as was male sex (OR, 1.7).

Older age (60 years or older) was meanwhile associated with a lower risk of growth than age younger than 45 years (OR, 0.5).

Among 184 patients (18.5%), nodules shrank spontaneously.

Thyroid cancer was diagnosed in five original nodules (0.3%); only two had grown from baseline. One incidental cancer was discovered upon thyroidectomy in a nonvisualized nodule.

Ninety-three patients (9.3%) developed new nodules over the course of the study, and among those, one cancer was detected.

Current guidelines recommend the repeating of thyroid ultrasonography after 6 to 18 months and, if the nodule size is stable, every 3 to 5 years thereafter. But the new findings support less frequent follow-up, suggesting safe management with a second ultrasound after the first, and, if no changes are detected, then reassessment after 5 years.

"The increased use of diagnostic imaging is bringing to light nodules that would never have been diagnosed in the past — some measuring even less than 1 cm," Dr Filetti said.

"Our findings show that very few of these nodules become cancers. This means they can be managed in a more relaxed fashion, which is not only less costly, but less of a burden for the patients."

Time to Change the Guidelines?

Last year, the American College of Radiology (ACR) issued a new white paper aimed at reducing the number of incidentally discovered thyroid nodules referred for further workup.

In an editorial accompanying this new study, Anne R Cappola, MD, and Susan J Mandel, MD, MPH, of the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, agree that current guidance can be relaxed. These new findings shed important light on the long-term progress of the benign thyroid nodule and send the strong message that routine fine-needle aspiration of such nodules is likely not productive.

"The practice of routine sonographic surveillance with repeat fine-needle aspiration for growth, as recommended by published guidelines, is not the most efficient strategy to detect the very small number of missed cancers among previously sampled cytologically benign nodules," they observe.

"The one-size-fits-all approach simply does not work. Instead, surveillance strategies should be individualized based on a nodule's sonographic appearance."

They add that the study provides further evidence that benign nodules, in most cases, can be expected to remain benign.

"Thyroid nodules are pervasive, whereas thyroid cancer is not," they state.

"The findings from [Dr] Durante et al represent an important step in improving the efficiency and mitigating the expense of follow-up for the vast majority of thyroid nodules that are either cytologically or sonographically benign."

The study received funding from the Umberto Di Mario Foundation, Banca d'Italia, and the Italian Thyroid Cancer Observatory Foundation. The authors, editorialists, and Dr Haymart have reported no relevant financial relationships.

JAMA. 2015;313:926-935, 903-904. Abstract, Editorial


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