ESTES PARK, COLO. – Before ordering any tests at all, an astute clinician can have a pretty good idea as to whether a palpable thyroid nodule is at higher or lower risk for being malignant based upon the patient’s history and physical examination, Michael T. McDermott, MD, said at a conference on internal medicine sponsored by the University of Colorado.

“The possibility of cancer is what scares people, and that’s what people want to know,” observed Dr. McDermott, professor of medicine and director of endocrinology and diabetes practice at University of Colorado Hospital.

This is a common clinical problem.

“If you felt the neck of every patient that you saw, 4%-7% would have a palpable thyroid nodule,” the endocrinologist said.

Moreover, upon imaging the thyroid by ultrasound, CT, or MRI, the prevalence of a thyroid nodule is close to 40%. And because the prevalence increases with age, thyroid nodules are found at autopsy in 50%-60% of individuals.

Ninety percent of thyroid nodules are benign. And even when they are malignant, for the most part the prognosis is very good. Ten-year survival is in excess of 90% in patients with papillary, follicular, or Hurthle-cell thyroid cancer and greater than 60% in the 2%-5% of thyroid cancers classified as medullary. The one bad actor is anaplastic thyroid cancer, with a 1-year survival rate of less than 5%; however, only 2%-5% of thyroid cancers are of the anaplastic type.

The cancer risk of a palpable thyroid nodule is increased if it is 3 cm or larger in size, of a firm and fixed consistency, or cervical lymph nodes are palpable. Clues of increased risk from the patient history include a family history of papillary or medullary thyroid cancer, compressive symptoms such as a mass sensation or difficulty swallowing, or radiation therapy to the head and neck before age 20 years for treatment of acne, ringworm, or for tonsil/adenoid shrinkage, a fairly common practice in the 1950s and 1960s.

The first test to order in evaluating a thyroid nodule is always a serum TSH. If the level is low or undetectable, that’s a relief: It is not cancer. A mildly elevated free T4 and total T3 in conjunction with the low TSH indicate an autonomously functioning nodule.

In this situation, the next test to order is a radioactive iodine uptake and scan.

“Every nuclear medicine department in the country does these,” Dr. McDermott observed.

A normal radioactive iodine uptake value is 20%-40%; however, in the setting of suppressed serum TSH, there is no physiologic stimulation for uptake, so any uptake would be considered inappropriately high and constitutes confirmation that this is a patient with hyperthyroidism.

If the serum TSH is normal or high, there is no need to order a free T4 and total T3. Instead, the next test to order is a neck ultrasound; the size and features of the nodule upon imaging will determine the need for fine needle aspiration as a next step in the evaluation. Ultrasound findings suggestive of malignancy are a dark, hypoechoic nodule with irregular margins, microcalcifications, and/or increased blood flow upon Doppler imaging.

“Patterns and combinations of findings are more informative than any single finding,” he said.

Fine needle aspiration pathology results are reported as benign, malignant, or indeterminate. If the report is benign, there is still about a 2.5% chance of malignancy due to sampling error.

Molecular markers have a role in the 30% or more of fine needle aspiration results labeled indeterminate based upon a finding of atypia of unknown significance, a follicular lesion of unknown significance, or a follicular neoplasm. The Afirma gene expression classifier (Veracyte) has a high negative predictive value because it identifies patterns of mRNA expression consistent with benign tumors. The ThyroSeq oncogene panel (Interspace Diagnostics) has a moderate negative predictive value but a high positive predictive value. The tests each run about $1,200, but they spare patients with indeterminate aspiration biopsy findings from additional invasive diagnostic procedures – and the tests are covered by insurers.

“The gene expression classifier is a good test when you’re trying to avoid surgery, and the oncogene panel tells you when you really need surgery,” Dr. McDermott explained.

He recommends as a thyroid screen palpating the thyroid as part of a routine annual physical exam and ordering a serum TSH every 5 years starting at age 50. He is opposed to proactive ultrasound imaging of the thyroid as a means of screening for thyroid cancer because that practice picks up a huge number of nonharmful nodules.

Dr. McDermott cited the current American Thyroid Association guidelines on the evaluation and management of thyroid nodules as “one of the most important recent developments in the field.” The guidelines include detailed evidence-based recommendations regarding initial evaluation, criteria for fine-needle aspiration biopsy, interpretation of the biopsy results, use of molecular markers, and management of benign thyroid nodules. The guidelines also address the initial management of thyroid cancer and surveillance for recurrent disease.

Dr. McDermott reported having no financial conflicts regarding his presentation.

bjancin@frontlinemedcom.com

Is that thyroid nodule malignant?