Thyrotropin serum levels and coexistence with Hashimoto’s thyroiditis as predictors of malignancy in children with thyroid nodules

Abstract

Thyroid cancer (TC) in childhood is a rare disease characterized by an excellent prognosis. Thyroid nodules in children, although less common than in adults, have a greater risk of malignancies, particularly in those cases associated with anamnestic, clinical and ultrasonographic risk factors. Among the factors, which have been found to be linked with an increased relative risk of TC in children, an important role seems to be possibly played by an underlying nodular Hashimoto’s thyroiditis (HT) and by the serum levels of TSH. Aim of this Commentary was to specifically address this last point. According to the available pediatric literature on the relationships between these risk factors and phenotypical expression of TC in children, it is possible to conclude that: 1) It is not completely clarified if HT per se predisposes to malignancy or if it represents an incidental histologic finding in cases with TC or if it may be the result of an immune response against tumoral cells. 2) It is unclear whether phenotypic expression of TC is more severe in the cases with associated HT but normal TSH serum levels. 3) Persistently elevated TSH levels play an independent role as predictors of the likelihood of TC, especially in children but also in adults. 4) Patients with nodular HT and subclinical hypothyroidism need to be treated with Levothyroxine in order to prevent the development of both TC and severe thyroid dysfunctions.

Interleukin-17 and vascular endothelial growth factor: new biomarkers for the diagnosis of papillary thyroid carcinoma in patients with Hashimoto’s thyroiditis

“… 3 , 4 There is thus a close relationship between the pathogeneses of these two diseases. Although the exact mechanism linking these diseases is not clear, there are currently three main hypotheses: 1) HT is a precancerous lesion of PTC; 2 , 23 2) the hypothesis of chronic inflammation; and 3) HT and PTC have common causes, potentially including immune factors (both thyroid globulin antibody and microsomal antibody have been found in the blood of HT and PTC patients), 24 – 26 endocrine factors (HT can cause hypothyroidism and increase reactive thyrotropin, which can in turn cause carcinogenesis), 27 – 31 and radioactive factors (exposure to X-rays can lead to thyroid inflammation and carcinogenesis, via the same mechanism). 32 – 37 …”

Evaluation of Children and Adolescents with Thyroid Nodules: A Single Center Experience

“…TSH has a major role on the proliferation and functioning of thyroid cell and persistently elevated TSH levels increase the risk of DTC formation ( 28 ). Even patients with a nodule and TSH levels in upper tertiles of reference range may have increased risk for malignancy ( 29 ).…”

“…Co-existence of DTC and HT has been reported in many publications ( 33 , 34 ). However, it is not clear whether lymphocytic infiltration due to HT facilitates DTC formation or the immune response against the tumour initiates lymphocytic infiltration ( 28 ). Adult studies that have investigated the prevalence of HT among patients with DTC have reported a variable prevalence of 5-85% ( 35 ).…”

Stress, Thyroid Dysregulation, and Thyroid Cancer in Children and Adolescents: Proposed Impending Mechanisms

“…Genetics differ in pediatric and adult TC [55]. Mutations in RAS, BRAF , PAX8 , or PPARG genes while frequently found in adults are rare in pediatric TC where RET/PTC , AKAP9–BRAF , and NTRK1 rearrangements prevail [28, 56].…”