3/5/2015
by Parker Brown Staff Writer, MedPage Today
Action Points
Note that this longitudinal cohort study of individuals with benign thyroid nodules found a very low rate of malignant transformation.
These results call into question the utility of routine follow-up screening of benign nodules.
A majority of asymptomatic, benign thyroid nodules either did not change in size or shrank after 5 years, and there were very few thyroid cancer diagnoses, according to a prospective study.
In almost 1,000 patients, significant growth of a thyroid nodule occurred in 15.4% of patients (95% CI 14.3-16.5), and 18.5% of the nodules shrank spontaneously (95% CI 16.4-20.9), reported Sebastiano Filetti, MD, of the Dipartimento di Medicina Interna e Specialita Medicha, in Rome, and colleagues.
In addition, 0nly seven patients (0.7%) of the patients received a thyroid cancer diagnosis, and in two of the cases the malignancy was from a thyroid nodule that wasn’t present at baseline. More than 9% of the patients developed new nodules, they wrote in the Journal of the American Medical Association.
“Current guidelines suggest, based on expert opinion, repeating thyroid ultrasonography after 6 to 18 months and, if nodule size is stable, every 3 to 5 years,” Filetti’s group stated. “These findings support consideration of revision of current guideline recommendations for follow-up of asymptomatic thyroid nodules.”
They analyzed sonographic findings to see how the incidence and size of thyroid nodules changed over 5 years, through Jan. 31, 2013. All 992 patients (mean age 52.4, 82% female) had one to four asymptomatic solid-cystic thyroid nodules with a fluid component of no more than 75% of the entire volume of the cyst.
None of the nodules contained evidence of malignancy, and none of the patients showed nodule-related signs or symptoms. Thirty percent of the group received levothyroxine therapy in the past.
“The biggest implication [of the findings] is how you can follow somebody over time once they’ve had that first ultrasound,” Anne Cappola, MD, of the Perelman School of Medicine at the University of Pennsylvania, told MedPage Today. “We’re getting better at figuring at who the people are we need to worry about.”
Cappola and Susan Mandel, MD, PhD, also from UPenn, authored an accompanying editorial, where they noted that another important finding was that an increase in nodule size was not predictive of malignancy.
They also pointed out that “these data suggest that sonographic surveillance for detection of a missed malignancy is not indicated for cytologically benign nodules that lack any of the accepted suspicious sonographic features as described by the authors: hypoechogenicity, irregular margins, taller-than-wide shape, intranodular vascularity, and microcalcifications.”
In the study, more than 150 patients experienced nodule growth, and 174 of the 1,567 baseline nodules (11.1%) increased in size. Growth was associated with the presence of multiple nodules (odds ratio 2.2, 95% CI 1.4-3.4) for two nodules, for three nodules (OR 3.2, 95% CI 1.8-5.6) and for four (OR 8.9, 95% CI 4.4-18.0). It was also associated with the male sex. An age of more than 60 was associated with a lower risk of growth.
Significant growth was defined by the American Thyroid Association guidelines as at least a 50% change in volume. Twenty one patients (22.3%) with two nodules saw significant growth. Growth was generally slow, with a mean 5-year largest diameter increase of 4.9 mm. Growth was least likely in patients whose largest nodule diameter was 7.5 mm or less, the authors stated.
The most relevant baseline characteristics — and ones that any revised guidelines might focus on — were multiple nodules, nodule diameter of 7.5 mm or more, and an age of 43 or less.
Forty percent of the nodules were classified as benign based on cytological findings at baseline; the others were classified as such on the absence of suspicious ultrasound features. Shorter follow-up times occurred in 117 cases because of loss to follow-up, death, and receiving a thyroidectomy.
The authors wrote that the data shows that a minority of thyroid carcinomas can be expected to grow slowly over time, and progress to clinical disease. “Only 2 of the 5 diagnoses of cancer in an established nodule were preceded by significant growth of the cancerous nodule,” they wrote. “These data suggest that the American Thyroid Association’s recommendation for indication for repeat cytology should be revised.”
Cappola and Mandel also said that routine sonographic surveillance is not the way to go. “The one-size-fits-all approach simply does not work,” they wrote. “Instead, surveillance strategies should be individualized based on a nodule’s sonographic appearance.”
Filetti and colleagues wrote that clinical and sonographic results should “probably play larger roles” when determining how to manage nodules.
Cappola told MedPage Today that from a patient perspective, the study results are reassuring.
“Every time [patients] get that follow-up ultrasound, they get nervous,” she explained. “And if we can appropriately reassure them, and show them these are the ones we worry about, these are the ones we don’t, I think that could help patients out a lot, as well as save costs.”
The researchers noted that all patients came from areas in Italy where iodine deficiency is a problem, so nodule growth might be different among other populations. In addition, the predictive modeling the researchers used hasn’t been externally validated, and the results might be prone to “overfitting.”
The study was funded by grants from the Umberto Di Mario Foundation, Banca d’ltalia, and the Italian Thyroid Cancer Observatory Foundation.
Filetti and co-authors disclosed no relevant relationships with industry.
Cappola and Mandel disclosed no relevant relationships with industry.
Reviewed by F. Perry Wilson, MD, MSCE Assistant Professor, Section of Nephrology, Yale School of Medicine and Dorothy Caputo, MA, BSN, RN, Nurse Planner
last updated 03.06.2015
Primary Source
Journal of the American Medical Association
Source Reference: Durante C, et al “The Natural History of Benign Thyroid Nodules” JAMA 2015;313:926-935.
Secondary Source
Journal of the American Medical Association
Source Reference: Cappola A and Mandel S “Improving the Long-term management of Benign Thyroid Nodules” JAMA 2015; 313:903-904.