Management of Thyroid Nodules
July 2015
Volume 6, Issue 3

The American Thyroid Association’s Guideline on Management of Pediatric Thyroid Nodules and Cancer

Thyroid. 2015;Apr 21:[Epub ahead of print]

In April 2015, the American Thyroid Association (ATA) Task Force on Pediatric Thyroid Cancer released management guidelines for children with thyroid nodules and differentiated thyroid cancer. Prior to the release of these guidelines, children with thyroid neoplasia were treated and followed according to the adult guidelines. However, thyroid neoplasia in childhood is associated with different pathophysiology, clinical presentation, and long-term outcomes, and treating children using the adult guidelines places children at risk for use of overly aggressive radiation therapy.

For example, using the adult guidelines, all children with thyroid neoplasia were required to undergo total thyroidectomy and radioactive iodine ablation. However, recent studies suggest that survivors of childhood differentiated thyroid cancer (DTC) are at increased risk for mortality, primarily because of malignancies in children treated with radiation. Thus, a primary goal of the pediatric guidelines was to help limit the use of aggressive therapy in children who are unlikely to benefit.

The following is a summary of recommendations 1-9 out of the 34 recommendations in the guidelines.

1-The pediatric guidelines apply to children ≤18 years of age. (Rating C) While most pediatric patients have completed their growth and development by the age of 18 years, the pediatric guidelines may be used to manage children with thyroid nodules anywhere between 18 to 21 years of age.

2-It is unknown whether children should be stratified into risk groups based on age (<10-15 years and 10-18 years). (Rating B) Current studies have not clearly shown whether or not younger children are at greater risk for more extensive disease or higher recurrence rates, and other risk factors than age may interact to modify this risk.

3-Children should be treated by interdisciplinary teams of physicians experience in the management of pediatric DTC to help maintain low rates of disease-specific mortality in children while reducing the likelihood of using overly aggressive or inadequate treatment. (Rating C) These teams should include high-volume thyroid surgeons, as well as experts in nuclear medicine and endocrinology with experience in treating pediatric DTC.

4-A) Children at high risk for thyroid neoplasia should undergo annual physical examinations. Children with any of the following findings on examination should undergo additional imaging studies: palpable nodules, thyroid asymmetry, and/or abnormal cervical lymphadenopathy. (Rating B) Risk factors for development of thyroid nodules in children include: iodine deficiency, prior radiation exposure (especially doses up to 20-29 Gy), a history of antecedent thyroid disease, a family history of familial non-medullary thyroid cancer, and certain genetic syndromes (ie, APC-associated polyposis, Carney complex, DICER1 syndrome, PTEN hamartoma tumor syndrome, and Werner syndrome).

4-B) It is unclear whether routine ultrasound (US) imaging should be used in children at high risk for thyroid neoplasia; more data becomes is needed on the long-term effects of this practice. (Rating I) Nodules detected incidentally should undergo ultrasound by an experienced ultrasonographer with fine-needle aspiration (FNA) performed on nodules with suspicious sonographic features or growth over time.

4-C) Children at increased risk of for familial DTC should be treated at centers of excellence. (Rating C)

4-D) Children with autoimmune thyroiditis in addition to a suspected nodule or significant gland asymmetry (particularly palpable cervical lymphadenopathy) on examination should be evaluated by an experienced thyroid ultrasonographer. (Rating B) FNA should be considered based on the presence of suspicious sonographic features or nodule growth over time.

5-The following recommendations for examination and treatment of pediatric thyroid nodules differ from adult guidelines (Rating B):

  • The decision to use FNA should be based on US characteristics and clinical context rather than size alone. Thyroid volume changes with age and the size of the nodule are not predictive of malignancy in children.
  • US guidance should be used during FNA in children because of the greater risk for malignancy and difficulty performing repeat FNA in children.
  • All hyperfunctioning nodules in children should be surgically removed.
  • Children with diffuse thyroid enlargement should be evaluated with imaging to assess for a diffusely infiltrative form of papillary thyroid cancer (PTC), particularly if palpable cervical lymph nodes are also present.
  • Nodules with indeterminate cytology should undergo lobectomy plus isthmusectomy rather than repeat FNA.

6-Molecular testing may aid in the management of nodules with indeterminate cytopathology, but these tools have not been sufficiently validated in children and cannot be routinely recommended until further studies are conducted. (Rating E)

7-No recommendation can be made at this time on the routine use of Levothyroxine (LT4) therapy. (Rating I) While data suggest that LT4 therapy may be effective in reducing the size and risk of subsequent nodule formation, the clinical benefit of this size reduction is unclear and there is little evidence of the long-term risks of this therapy in children.

8-Serial US should be used to evaluate benign lesions, with repeat FNA performed if the lesion continues to grow or develops suspicious features. Lobectomy may be performed for patients whose nodules increase in size or who have compressive symptoms, cosmetic concerns, or who prefer surgery. Lobectomy should be considered for benign solid nodules >4 cm, with significant growth, or in children with other risk factors for malignancy. (Rating B) Lobectomy is preferred to minimize the complication risk.

9-Thyroid scintigraphy should be used in children who present with a suppressed thyroid stimulating hormone (TSH) associated with a thyroid nodule to diagnose an autonomously functioning nodule. If diagnosis is confirmed, surgical resection (most commonly lobectomy) is recommended. (Rating A). Increased uptake on a nuclear medicine radioisotope scan is used to diagnose an autonomously functioning nodule (ie, toxic adenoma).

The ratings used by the ATA in the pediatric guidelines are as follows:

  • A = strongly recommends.
  • B = recommends.
  • C = recommends.
  • D = recommends against.
  • E = recommends against.
  • F = strongly recommends against.
  • I = recommends neither for nor against.

Commentary

Dr. Priyathama Vellanki is an Assistant Professor, Division of Endocrinology, Metabolism and Lipids at Emory University School of Medicine in Atlanta, GA.

Thyroid nodules are less prevalent in children compared to adults. However, the prevalence of thyroid cancer is higher (~25%) in children compared to adults (~5%).1 The reason for these differences is likely that children with thyroid nodules usually have factors that put them at high risk for cancer, such as radiation exposure for treatment of childhood malignancy or genetic mutations. Furthermore, the correlation of indeterminate cytology diagnosis by the Bethesda criteria to malignancy is different in children compared to adults.2 In spite of this difference, there were no separate guidelines for the management of pediatric thyroid nodules and cancers until the 2015 guidelines were published by the American Thyroid Association (ATA). While the literature on the management of pediatric thyroid nodules is not as extensive as in adults, the ATA's guidelines highlight the differences in management between adult and pediatric populations.

Overall, because of the higher prevalence of cancer in pediatric thyroid nodules, the ATA recommends more aggressive treatment. Unlike the adult guidelines, which suggest a repeat fine-needle aspiration (FNA) for indeterminate nodules, the pediatric guidelines recommend diagnostic lobectomy. The ATA guidelines also suggest that children with nodules >4 cm need to undergo diagnostic lobectomy because of the risk of a false-negative FNA result. Furthermore, molecular testing, which has only been validated in a small cohort of 5 children, is not recommended in children.3 The recommendation for benign nodules in children is similar as that stated in the adult guidelines: monitor using serial ultrasound. Long-term prospective trials, as performed in adults, are needed to validate these recommendations and to improve the case of pediatric patients with benign nodules.

References
1. Buryk MA, Simons JP, Picarsic J, Monaco SE, et al. Can malignant thyroid nodules be distinguished from benign thyroid nodules in children and adolescents by clinical characteristics? A review of 89 pediatric patients with thyroid nodules. Thyroid. 2015;25:392-400.

2. Norlen O, Charlton A, Sarkis LM, Henwood T, et al. Risk of malignancy for each Bethesda class in pediatric thyroid nodules. J Pediatr Surg. 2015;50:1147-1149.

3. Buryk MA, Monaco SE, Witchel SF, Mehta DK, et al. Preoperative cytology with molecular analysis to help guide surgery for pediatric thyroid nodules. Int J Pediatr Otorhinolaryngol. 2013;77:1697-1700.

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American Thyroid Association Statement on Using Molecular Profiling for Perioperative Decision-Making on Thyroid Nodules
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