Updated Guidelines for the Treatment of Thyroid Nodules

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Richard T. Kloos, MD, discusses new technologies and methods for diagnosis of thyroid nodules.
Richard T. Kloos, MD, discusses new technologies and methods for diagnosis of thyroid nodules.

At the ICE/ENDO 2014 spring meeting, the American Thyroid Association (ATA) previewed updated, preliminary guidelines for the clinical management of patients with thyroid nodules and differentiated thyroid cancer.

The ATA was prompted to update their guidelines based on the significant amount of new information and clinical evidence — as well as validated new technology — available since the 2009 published guidelines.

Diagnostic ambiguity historically has been a significant problem in thyroid nodule diagnosis, resulting in unnecessary surgeries and health care costs among the more than half a million U.S. patients who undergo fine needle aspiration (FNA) biopsies each year to rule out thyroid cancer.

Published data suggest that 15% to 30% of people in the United States whose FNAs are evaluated by cytopathology alone receive diagnostically ambiguous, or “indeterminate,” results.1 

Guidelines have traditionally recommended that these patients undergo a partial or complete thyroidectomy for final diagnosis. Unfortunately, such surgery is invasive, costly and often results in lifelong thyroid hormone therapy. Most troubling, 70% to 80% of these patients — literally tens of thousands of people — ultimately have benign nodules and therefore could have avoided surgery and its lifelong implications.2,3

Fortunately, medical practice and medical technology have evolved dramatically in recent years to begin addressing this long-standing challenge.

Papillary thyroid cancer is by far the most common thyroid malignancy, and physicians increasingly recognize that in the absence of macroscopic lymph node metastases, these malignancies are typically indolent. This recognition is part of a larger trend towards less aggressive treatment of thyroid cancer and greater interest in intervening only when the patient will benefit.

There has also been dramatic progress in diagnostic capabilities and technology. Thyroid nodule FNA samples are often challenging to interpret using cytopathology alone. But recent studies have shown that thyroid-specialist cytopathologists — i.e., those who specialize in thyroid FNA cytology and interpret a lot of them — may make definitive diagnoses on a higher percentage of benign and malignant cases.4,5,6

RELATED: Evaluating Benign Thyroid Nodules: The Appropriate Time Interval After Initial Fine Needle Aspiration

For biopsies that are cytologically indeterminate, molecular testing has demonstrated both real-world validity and utility in reducing the number of patients who require surgery to resolve their nodule status.

Two main categories of molecular tests are currently commercially available: Those that “rule in” cancer (i.e., those designed to confirm malignancy) and those that “rule out” (i.e., those designed to confirm an FNA sample is benign). The former may help to inform the extent of surgery needed, while the latter helps prevent unnecessary surgery. No single test currently provides both of these capabilities.

The ATA's preliminary guidelines (final guidelines are expected early this year) recommend that molecular testing may be used to guide decision-making around the two major categories of cytologically indeterminate thyroid nodules: atypia of undetermined significance/ follicular lesion of undetermined significance (AUS/FLUS; Bethesda III) and follicular neoplasm/suspicious for follicular neoplasm (FN/SFN; Bethesda IV).

Specifically, the preliminary guidelines recommend that when the primary goal is to avoid unnecessary surgery, a molecular test with high sensitivity and high negative predictive value (NPV) should be considered (i.e., a “rule out” test). While testing for malignancy (a “rule in” test) can help identify when a cancer is present, these malignancy markers currently miss more than 50% of cancers with indeterminate cytology.7

Accordingly, they are unable to move a patient from surgery to routine monitoring. They may, however, help physicians preoperatively plan the extent of surgery needed for each patient.

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