2022 European Thyroid Association Guidelines for the management of pediatric thyroid nodules and differentiated thyroid carcinoma

Abstract

At present, no European recommendations for the management of pediatric thyroid nodules and differentiated thyroid carcinoma (DTC) exist. Differences in clinical, molecular, and pathological characteristics between pediatric and adult DTC emphasize the need for specific recommendations for the pediatric population. An expert panel was instituted by the executive committee of the European Thyroid Association including an international community of experts from a variety of disciplines including pediatric and adult endocrinology, pathology, endocrine surgery, nuclear medicine, clinical genetics, and oncology. The 2015 American Thyroid Association Pediatric Guideline was used as framework for the present guideline. Areas of discordance were identified, and clinical questions were formulated. The expert panel members discussed the evidence and formulated recommendations based on the latest evidence and expert opinion. Children with a thyroid nodule or DTC require expert care in an experienced center. The present guideline provides guidance for healthcare professionals to make well-considered decisions together with patients and parents regarding diagnosis, treatment, and follow-up of pediatric thyroid nodules and DTC.

Keywords: European; pediatric; recommendation; thyroid cancer; thyroid nodule.

Figure 1

Flowchart of initial evaluation, treatment, and follow-up of the pediatric thyroid nodule. ^#The expert panel suggests considering the measurement of serum calcitonin in children suspect of MTC based on individual conditions and the preference of the physician (Recommendation 5A). The expert panel suggests that, in selected cases (conditions which suggest MEN2, a positive family history of MEN2, or in case of bulky thyroid disease), measurement of calcitonin may be of additional value for early diagnosis of MTC (Recommendation 5B). ^*Malignancy risk (suspicious vs no suspicion) is based on neck ultrasound characteristics (37), section ‘B2. Risk of malignancy in a thyroid nodule during childhood’), history of radiation, and (signs of a) pre-disposition syndrome. If there is a significant increase in nodule size or the ultrasound characteristics change over time, (repeated) FNB should be performed. ^**Analysis of the presence of other oncogenic drivers and gene fusions (e.g. RET/PTC and NTRK-fusions) may be considered in Bethesda 3, 4, or 5 due to the fact of increasing awareness that these are also associated with the presence of PTC (39). In case a BRAF V600E mutation is found, the risk of the thyroid nodule being malignant is high but needs to be confirmed, for example, by frozen section during thyroid surgery. ^{^}Total thyroidectomy after proven presence of MTC. ^{^^}Alternatively, FNB can be performed; in case of DTC, a total thyroidectomy should be performed.

Figure 2

Flowchart of surgical approach for DTC in children. BCLND, bilateral central lymph node dissection; CLND, central lymph node dissection; DTC, differentiated thyroid carcinoma; FNB, fine needle biopsy; ICLND, ipsilateral central lymph node dissection. ‘Active surveillance’ in low-risk DTC implies ultrasound of the leftover thyroid tissue, including the evaluation of the cervical lymph nodes every 6–12 months by neck palpation and ultrasound.

Figure 3

Flowchart of follow-up of children with DTC having received complete remission after initial treatment with total thyroidectomy and I-131. This flowchart is developed for children with DTC having received complete remission defined as: undetectable levels of serum Tg on LT4, undetectable levels of Tg antibodies, negative neck ultrasound, and if performed, negative whole-body scan 1 year after last treatment. ^{^}In the first year until clinical remission, TSH levels should be suppressed, while a normal low value of TSH (between 0.5 and 1.0 mU/L) will be advisable thereafter. ^{^^}The definition of consistent rising Tg on LT4 is debatable; the levels of Tg as well as the doubling time should be taken into account and weighted in the individual patient. ^*The expert panel suggests that, in children with detectable (but not rising) Tg and no focus on neck ultrasound, in individual cases, I-123 scanning may be considered. When both ultrasound and radioiodine imaging did not yield a focus, FDG PET/CT may be considered.