Standardized Testing: Universal Risk Stratification System Needed for Thyroid Nodules

With thyroid cancer patients often getting different — and sometimes conflicting — treatment recommendations from a variety of diagnostic tools, Priyanka Majety, MD, talks to Endocrine News about why it’s time for clinicians to coalesce around a single set of standards for these cases, which could potentially eliminate unnecessary procedures.

Priyanka Majety, MD, assistant professor in the Division of Endocrinology, Diabetes, and Metabolism at Virginia Commonwealth University in Richmond, vividly remembers seeing a patient with a family history of thyroid cancer, who presented with a sub-centimeter thyroid nodule, in her training.

When the team input the patient’s history and ultrasound findings into different risk-stratifying tools, the recommendations about next steps varied, based on the tool used. Some tools recommended no biopsy; others recommended considering a biopsy or monitoring the nodule with a repeat ultrasound after a certain interval.

“After a detailed discussion with the patient, given her family history of lethal thyroid cancer at her request, we biopsied the nodule which turned out to be malignant,” Majety says. “She underwent surgery and is doing well but this case highlights the discrepancy between recommendations, based on the inclusion or exclusion of clinical features and variability in ultrasound size cut-offs informing guidance regarding biopsy.”

About half the population will develop a thyroid nodule by age 60; up to 90% of these are benign. Most thyroid cancers are low-risk neoplasms that usually do not have an impact on survival. Diagnosing and treating these include not only a physical examination but also an ultrasound of the nodule(s), followed by a biopsy, which can have a detrimental effect on the patient’s emotional and financial status. Majety says that in the United States, more than 500,000 fine needle aspirations (FNAs) are done each year, and about 200,000 of them turn out to be unnecessary.

A Need for Uniformity

According to Majety, evaluation of patients with suspected thyroid nodules must include a thorough medical history and physical examination and a thyroid-stimulating hormone (TSH) level and ultrasound evaluation. Based on the size of the nodules and other characteristics on ultrasound, providers estimate the risk of these nodules being malignant.

“It is important to identify the nodules at the highest risk of malignancy. Currently, there are several risk stratification tools including clinical practice guidelines, scoring systems, web-based calculators, and an interactive algorithm, available to clinicians. This poses a unique challenge to not just the clinicians but also the patients, due to the lack of uniformity in the recommendations.” — Priyanka Majety, MD, assistant professor, Division of Endocrinology, Diabetes, and Metabolism, Virginia Commonwealth University, Richmond, Va.

To stratify the risk of malignancy, various tools are available, but there are considerable differences among these tools — they differ in their formats (pattern recognition versus point systems), risk categories, FNA size thresholds, and recommended surveillance intervals. Multiple studies have compared various risk stratification tools, and no single system has consistently demonstrated superiority over the others.

“It is important to identify the nodules at the highest risk of malignancy,” Majety says. “Currently, there are several risk stratification tools including clinical practice guidelines, scoring systems, web-based calculators, and an interactive algorithm, available to clinicians. This poses a unique challenge to not just the clinicians but also the patients, due to the lack of uniformity in the recommendations.”

In June 2023, Majety’s paper, “Thyroid Nodules: Need for a Universal Risk Stratification System” appeared in a special issue of Frontiers in Endocrinology, “Thyroid Nodule Evaluation: Current, Evolving and Emerging Tools.” The issue highlighted the challenges faced by clinicians in this field, and how those challenges are currently being addressed.

Majety writes that using multiple risk stratifying systems (RSSs) can lead to confusion at times. The varied RSSs can affect clinicians in training as well, since their attendings may have different approaches. She explains that radiologists and endocrinologists typically use different guidelines for risk stratification, which can lead to unnecessary time consumption, as physicians have to re-review those nodules and stratify risk using a different tool.

“Endocrinology fellows in training tend to work with several teaching attendings, and many of them have a different approach to thyroid nodule evaluation, the biggest difference being the risk-stratifying system in use,” Majety says. “Some of the senior physicians tend not to use any system but go with their intuition while other physicians use different systems, reflective of the differences in their training and experience. It can sometimes be an overwhelming and confusing experience.”

Reducing Unnecessary Biopsies

Currently, there are several RSSs across the globe, varying by country and professional organization, and clinicians choose which tool to use based on geography and specialization. There are other RSSs that are developed by groups of investigators who do not represent any professional organization. “It is a huge undertaking to bring all the professional societies together and develop a universal risk-stratifying system that they all agree upon” Majety says. “Even if one such universal tool is developed, it would still need to be validated in large multi-regional population studies before clinicians can use it.”

Another major challenge, Majety says, of ultrasound-based risk-stratifying systems is the inter- and intra-observer variability. There are still inconsistencies in thyroid US examiners’ reporting and rating abilities. “One potential solution to all these challenges is a unified lexicon of thyroid US features and dedicated training,” she says.

“There is a strong need for a universal RSS with a lexicon to harmonize all the current systems and standardize the evaluation of thyroid nodules with the aim of reducing unnecessary thyroid biopsies without jeopardizing the detection of clinically significant malignancies. Until this ideal tool is developed, clinicians should continue to use the tools available and individualize the management based on individual risk factors.” — Priyanka Majety, MD, assistant professor, Division of Endocrinology, Diabetes, and Metabolism, Virginia Commonwealth University, Richmond, Va.

For Majety, her ideal RSS would minimize the number of unnecessary biopsies and identify all clinically significant thyroid cancers, leading to lower healthcare costs and morbidity. “The goal is to develop a universal risk stratification system that identifies all clinically significant thyroid cancers and that would help not only clinicians but also patients in understanding ultrasound reports and making appropriate recommendations in identifying the nodules that require further evaluation including a biopsy,” she says.

Majety points to a grassroots initiative, managed by the steering committee of the International Thyroid Nodule Ultrasound Working Group (ITNUWG), is currently working to develop an international system, termed I-TIRADS, that integrates the leading risk-stratifying systems.

“There is a strong need for a universal RSS with a lexicon to harmonize all the current systems and standardize the evaluation of thyroid nodules with the aim of reducing unnecessary thyroid biopsies without jeopardizing the detection of clinically significant malignancies,” Majety continues. “Until this ideal tool is developed, clinicians should continue to use the tools available and individualize the management based on individual risk factors.”

Bagley is the senior editor of Endocrine News. In the November issue, he wrote about potential pharmacological options for preventing diabetes.

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