FROM THYROID

The evaluation and treatment of thyroid nodules in children should differ from evaluation and treatment in adults in that ultrasound characteristics and clinical context should be used rather than size alone to identify nodules that warrant fine-needle aspiration, according to new pediatric-specific guidelines from the American Thyroid Association.

The Management Guidelines for Children with Thyroid Nodules and Differentiated Thyroid Cancer – the first-ever guidelines for the evaluation and management of thyroid nodules and cancer in children – also note that fine-needle aspiration (FNA) in children should be performed under ultrasound guidance, that preoperative FNA of a hyperfunctioning nodule in a child is not warranted as long as the lesion is removed, that a diffusely infiltrative form of papillary thyroid cancer may occur in children and should be considered in a clinically suspicious gland, and that surgery (lobectomy plus isthmusectomy) is favored over repeat FNA for most nodules with indeterminate cytology, Dr. Gary L. Francis of Virginia Commonwealth University and Children’s Hospital of Richmond, Va., and his colleagues from the American Thyroid Association Guidelines Task Force on Pediatric Thyroid Cancer determined based on an extensive literature search.

Together this guidance with respect to thyroid nodules represents just one of 34 recommendations contained in the guidelines, which, according to the authors, represent “the current optimal care for children and adolescents with these conditions.”

The guidelines were published in the July issue of Thyroid (2015;25:716-59).

Previous guidelines were geared toward adults, but thyroid neoplasms in children differ from those in adults with respect to pathophysiology, clinical presentation, and long-term outcomes. Further, therapy that may be appropriate in adults may not be appropriate for children at low risk for death but higher risk of long-term harm from certain treatments, they said.

For example, recent studies with long-term follow-up revealed an increase in all-cause mortality for survivors of childhood differentiated thyroid cancer (DTC), primarily caused by second malignancies in children treated with radiation.

“These observations, coupled with a better understanding of the excellent prognosis associated with pediatric DTC, have now prompted the American Thyroid Association to specifically address treatment of children with benign and malignant thyroid tumors,” they wrote.

While the task force acknowledged a paucity of randomized, double-blind, controlled clinical trials involving children with DTC, they note that “retrospective analysis of therapeutic options has led to a reconsideration of the former concept that all children with DTC should be similarly treated and has provided the opportunity … to broaden the scope of acceptable therapy in an attempt to provide aggressive therapy when warranted and to limit overtreatment to those children who are unlikely to benefit.”

In addition to addressing the evaluation and management of thyroid nodules, the guidelines also address DTC, including preoperative staging, surgical management, postoperative staging, the role of radioactive iodine therapy, and goals for thyrotropin suppression. Management algorithms are proposed, and separate recommendations for papillary and follicular thyroid cancers are provided.

The authors note that since DTC recurrence has been reported as long as 40 years after initial therapy, children with DTC should be “followed for life, albeit with decreasing intensity for those with no evidence for disease.”

The guidelines are timely, as Surveillance, Epidemiology and End Results (SEER) program data indicate that new cases of thyroid cancer in persons under the age of 20 years represent 1.8% of all thyroid malignancies diagnosed in the United States, and that the incidence appears to be increasing.

Among 15- to 19-year old adolescents, thyroid cancer is the eighth most frequently diagnosed cancer, and it is the second most common cancer among girls, the authors said, noting that adolescents have a 10-fold greater incidence than do younger children, and that there is a female to male preponderance.

The development of pediatric-specific guidelines was critical, according to guidelines coauthor, Dr. Peter Angelos, professor of surgery and surgical ethics and chief of endocrine surgery at the University of Chicago Medicine and Biological Sciences.

“As they say, ‘children are not just small adults,’ ” he said in an interview.

In addition to the guidance provided on which types of nodules should be evaluated in children (since size alone should not be used to dictate who undergoes biopsy), a highlight of the guidelines is a recommendation that children with thyroid cancer be treated by multidisciplinary teams of physician in high-volume centers, he said.

“Thyroid cancer in children is different than in adults in that children have much higher rates of involved lymph nodes, but their overall prognosis is excellent despite the frequency of involved nodes. This confluence of findings pushes surgeons to do more aggressive operations to clear lymph nodes. This is a good thing, but unfortunately, can lead to higher complication rates (things such as permanently low calcium levels in the blood),” he said, adding that “the implications of finding a high-volume thyroid cancer surgeon with experience in thyroid cancer surgery on children are very significant and the guidelines make some recommendations about how many operations are necessary to constitute high volume.”

The push to limit the use of radioactive iodine in children further underscores the need for an experienced surgeon, he said.

“In an effort to avoid exposing children to radiation, surgeons are further pushed to be more aggressive in the operating room. Thus, it becomes even more important to see an experienced surgeon so that complications can be minimized. Even a seemingly ‘mild’ complication can be devastating for a child who will likely have to live with that complication for decades to come since the prognosis for thyroid cancer is so good,” he said.

An important potential benefit of treatment at centers with multidisciplinary interest and expertise is facilitation of additional research, particularly in areas of uncertainty, including the proper use of 131I, the interpretation of thyroglobulin (Tg) and TgAb (antibody) levels, the role of prospective ultrasound monitoring in presymptomatic children at risk for thyroid neoplasia, the use of novel targeted therapies for advanced disease that fails to respond to 131I, and the long-term psychosocial impacts of the disease on children and their families, the guideline authors said.

“These areas require well-designed long-term, multicenter studies that will be difficult to perform because of the rarity of pediatric DTC and the prolonged follow-up required to reach meaningful endpoints. Further research should be facilitated by ensuring that children with DTC are treated when possible at centers with multidisciplinary interest and expertise in this disease,” they concluded.

The guidelines were funded by the American Thyroid Association and ThyCa: Thyroid Cancer Survivors’ Association. Dr. Francis reported serving as an adviser to ThyCa and receiving research support from Grifols, Novo Nordisk, and the Juvenile Diabetes Research Foundation. Other authors reported relationships (consulting, receiving research support, and/or serving as a speaker) with Akrimax, IBSA Institut Biochimique, Pfizer, Novo Nordisk, Eli Lilly, AstraZeneca, Bayer Healthcare, Genzyme, Sobi, Henning, and Merck, and ThyCa.

sworcester@frontlinemedcom.com

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