Abstract
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The incidence of thyroid nodules is lower in children as compared to adults. In a study of schoolchildren aged 11–18 years of age in the Southwestern United States, nodules were detected in 1.8% by palpation (5). In a study of healthy Greek schoolchildren aged 5–18 years, nodules were present in 5.1%, as determined by an ultrasound (US) examination (6). By comparison, studies in adults report that thyroid nodules are present in approximately 10% of young adults and >50% of adults aged 60 years and older, as determined by US examination (7).
Conversely, the percentage of thyroid nodules harboring cancer is reported to be higher in children compared with adults. A review of 18 published studies totaling 1134 children reported cancer ranging from 9.2% to 50%, averaging 26.4% overall (8). This compares to the commonly quoted “5% of thyroid nodules are cancer in adults” (9). Although this would appear to represent a fivefold increased risk of cancer in nodules in children, a study employing a “standardized assessment of thyroid nodules” from Boston reported cancer in 22% of children versus 14% in adults (10), closer to a twofold increased risk.
Emphasizing another difference, the task force recognized that the size criterion (>1–1.5 cm) for obtaining tissue for pathologic evaluation via fine-needle aspiration (FNA) may not be appropriate in a growing child whose thyroid gland may be half the size of an adult. The task force therefore recommends that “US characteristics and clinical context should be used rather than size alone to identify nodules that warrant FNA” (4). Further, the task force recommends that all FNA in children be performed under US guidance. In the context of FNA, the task force acknowledges that while molecular testing aids management decisions in adults with indeterminate cytology, insufficient data exist in children and so its use in “routine clinical practice” cannot be recommended “until further studies are conducted” (4).
Management of autonomously functioning (“hot”) nodules likely represents another difference in children compared with adults. In both age groups, initial treatment may be aimed at controlling the hyperthyroidism. In adults, as the risk of cancer in “hot nodules” is quoted to be in the 3% range (11), resection or radioactive iodine ablation may not be considered initially. By contrast, up to 30% of children may be found to have incidentally discovered DTC in autonomous nodules (12). Thus, the guidelines for children recommend surgical resection at presentation for most cases. If surgery is deferred, for example, in cases of subclinical hyperthyroidism, the task force recommends that FNA be considered if the nodule has features suspicious for PTC (4).
Epidemiologic studies show that the incidence of thyroid cancer rises with age; for example, in those aged 10–14 years, there are 0.35 cases/100,000, while in those aged 25–29 years, there are 6.08 cases/100,000 (13). Studies also appear to show that there is an increasing incidence of DTC in both children and adults in the United States, with an annual percentage change of 3–4% between 1984 and 2010 for both groups (13). There are some differences in the frequency of pathologic types of thyroid cancer in children and adults. PTC is more common in children (∼95% vs. 80%), follicular thyroid carcinomas occur in approximately 5% in both, while Hürthle cell and anaplastic thyroid carcinoma are rare in children (14,15).
PTC is more likely to be multifocal, and more likely to have regional lymph node and distant metastases at presentation in children. At diagnosis, lymph node metastases are present in up to 78% of cases (16), and pulmonary metastases are present in approximately 9–30% of cases (17). Despite more widespread cancer at presentation, children with DTC have an excellent prognosis. Survival up to 10 years is typically 98% (13), while another study reported a cause-specific mortality of only 2% at 40 years' follow-up (16). However, while death from PTC is low, long-term studies report a higher than predicted number of deaths between 30 and 50 years' follow-up (16). In this analysis of all-cause mortality, two-thirds of the deaths resulted from non-thyroid second primary malignancies, and three-quarters of these patients had received some form of postoperative therapeutic irradiation (16). Recognizing these issues, a major goal of the task force was to try and define cases where aggressive therapy is indicated, and, conversely, to limit over-treatment in those children who are unlikely to benefit. To this end, the task force developed three risk levels of thyroid cancer (see table 6 in reference (4)). In those children deemed at low risk, defined by cancer confined to the thyroid gland, with no or only microscopic metastases to a small number of central neck lymph nodes, and with a stimulated postoperative serum thyroglobulin <2 ng/mL, the task force concluded that postoperative 131I treatment was not indicated (4).
While these guidelines are made on the best available current evidence, the task force recognized that the changes recommended may generate some uncertainty in treating physicians. Many questions require more research to generate answers; examples include whether molecular studies prove useful in cases with “indeterminate” cytopathology by FNA; which group at risk for thyroid nodules and DTC (e.g., children treated with radiation for head and neck tumors; children with genetic thyroid tumor syndromes) should be monitored by neck palpation versus US; which patients can safely be managed without postoperative 131I treatment; and what levels of serum thyroglobulin (basal or stimulated) or changes in thyroglobulin antibody titer indicate a need for further evaluation or additional treatment. As the incidence of thyroid nodules and cancer is lower in children as compared to adults, many physicians often have experience with a limited population of such patients. Thus, where possible, the task force recommends that children with DTC be evaluated and treated at centers with multidisciplinary interest and expertise in thyroid cancer.
In summary, the task force should be congratulated for developing the first set of guidelines specific to children. They address a significant need and will serve as a great resource to pediatric endocrinologists and other members of the multidisciplinary team, and likely they will improve the overall health and survival of children with thyroid nodules and DTC.