Research News

Patients with PTEN hamartoma tumor syndrome (PHTS) may require less frequent thyroid cancer surveillance than current guidelines recommend, according to a new study led by Charis Eng, MD, PhD, Chair of the Genomic Medicine Institute. Published in Thyroid, the study findings support a change in clinical practice that would decrease the burden of annual thyroid cancer surveillance ultrasounds, especially in young children and adolescents.

PHTS refers to a spectrum of rare genetic disorders characterized by germline (heritable) mutations of the tumor suppressor gene PTEN that increase the risk of certain cancers, cognitive and behavioral deficits, benign growths and tumors (i.e., hamartomas), and macrocephaly. Individuals with PHTS have a 35% lifetime risk of developing thyroid cancer compared to the 1% risk for those in the general population.

Clinicians use thyroid ultrasounds to diagnose and monitor the progression of thyroid cancer and thyroid nodules that may develop into cancer in PHTS patients. However, because there is minimal data on development and progression of thyroid cancer in PHTS, a consensus on the time of initiation and frequency of thyroid cancer surveillance has not yet been reached.

“Most guidelines recommend annual thyroid ultrasounds, but when to initiate these ultrasounds can range from shortly after birth to 18 years of age,” said Dr. Eng. “Surveillance recommendations also are typically applied to all PHTS patients, regardless of the presence or absence of thyroid nodules at the initial ultrasound, which can result in unnecessary stress and financial burden for certain patients.”

Here, the researchers examined the development and progression of thyroid nodules and thyroid cancer in PHTS patients in order to help refine surveillance recommendations. They specifically focused on pediatric, adolescent and young adult PHTS patients, who are more likely to have ultrasounds without nodules and stand to benefit the most from reduced surveillance.

Looking at 76 PHTS patients who had undergone at least two thyroid ultrasounds, they found that patients with an initial ultrasound without nodules had a greater than 90% likelihood of remaining free of a clinically actionable nodule after three years and an 85% likelihood after six years. No cases of thyroid cancer were diagnosed in this group over the entire follow-up period.

“Our findings strongly support that PHTS patients with a normal thyroid ultrasound do not need to undergo annual surveillance,” said Dr. Eng. “Our study suggests that the timing of surveillance should be recommended based on thyroid ultrasound results, and supports extending surveillance intervals to 3-5 years in PHTS patients without nodules and 2-3 years in those with clinically nonactionable nodules.”

Dr. Eng is Chair and Director of the Center for Personalized Genetic Healthcare, which includes the PTEN Multidisciplinary Clinic (designated as a PHTS Clinical Center of Excellence by the PTEN Hamartoma Tumor Syndrome Foundation) for children and adults with a confirmed or possible diagnosis within the PHTS spectrum. She was the first to link PTEN to Cowden syndrome, which is a PHTS disorder.

Gilman Plitt, MD, a PRISM (Physicians Researchers Innovating in Science and Medicine) scholar in the Eng lab and surgical resident in the Digestive Disease & Surgery Institute, is first author on the study, which was supported in part by the Ambrose Monell Foundation and the Cleveland Clinic Crile Research Fellowship.