Influence of Hashimoto Thyroiditis on the Development of Thyroid Nodules and Cancer in Children and Adolescents

Giorgio Radetti; Sandro Loche; Valeria D'Antonio; Mariacarolina Salerno; Chiara Guzzetti; Tommaso Aversa; Alessandra Cassio; Marco Cappa; Roberto Gastaldi; Filippo Deluca; Maria Cristina Vigone; Giulia Maria Tronconi; Andrea Corrias


J Endo Soc. 2019;3(3):607-616. 

In This Article

Abstract and Introduction


It is unclear whether patients with Hashimoto thyroiditis (HT) are predisposed to develop thyroid nodules and/or thyroid cancer. The objective of our study was therefore to assess the prevalence of thyroid nodules and/or cancer in patients with HT and to look for possible prognostic factors. A retrospective survey of 904 children/adolescents with HT (709 females, 195 males) regularly followed in nine Italian centers of pediatric endocrinology was performed. Median period of follow-up was 4.5 years (1.2 to 12.8 years). We evaluated free T4, TSH, thyroid peroxidase antibody (TPOAb), thyroglobulin antibodies, and thyroid ultrasound yearly. One hundred seventy-four nodules were detected, with an annual incidence rate of 3.5%. Ten nodules were malignant (8 papillary and 2 papillary follicular variant), giving a 5.7% prevalence of cancer among patients with nodules. The severity of hypoechogenity at ultrasound, TPOAb, and free T4 serum concentrations were predictive for the appearance of new nodules. Furthermore, a positive correlation was observed between TPOAb titer and the development of thyroid cancer. In conclusion, HT seems to influence the development of thyroid nodules, but not cancer in children and adolescents.


It is unclear whether patients with Hashimoto thyroiditis (HT) are predisposed to the development of thyroid nodules and/or thyroid cancer. Different approaches have led to discordant findings in adult subjects. A clear association between HT and differentiated thyroid cancer (DTC), mainly papillary, has been reported in surgical series.[1–6] However, this association was not found in patients with nodular pathology without suspicion of malignancy who underwent fine needle biopsy (FNA) and cytological studies[7–13] Because the surgically treated patients are those considered at higher risk of malignancy, the association between HT and DTC based on surgical pathology may be secondary to selection bias.

Nodular pathology and cancer are rarely observed in children and adolescents compared with the adult population. In a survey of 5179 healthy children performed in 1975, Rallison et al.[14] reported a frequency of nodules of 1.8%. However, in this study the presence of thyroid nodules was assessed by the poorly sensitive method of palpation. Furthermore, the prevalence of autoimmunity has increased in recent decades and so it may no longer be appropriate to make comparisons to a study performed more than 40 years ago. More recent studies that use ultrasound imaging, reported a prevalence of 0.2% to 5.1%.[15–17]

Thyroid nodules in children carry a greater risk of malignancy compared with adults.[18] However, there are few published data on the frequency of the development of thyroid cancer in children and adolescents with thyroid nodules. Niedziela[19] reviewed 18 studies published between 1960 and 2004 and reported a frequency of 9.2% to 50% based on surgical specimens. More recently, studies based on cytological/histological evaluation reported a frequency of more than 16%,[20–22] which is greater than that seen in adult patients (2.3%).[23,24]

Nethertheless, thyroid cancer is a rare condition in children and adolecents with an average age-adjusted rate of 0.59 per 100,000 cases.[25] A higher prevalence of up to 36 to 48 per 100,000 can be found in children exposed to radiation, such as in Fukushima after the Fukushima Daiichi nuclear power plant accident.[26] Whether the presence of HT influences the development of nodules and/or cancer in children is even more debated. The data are of poor quality, usually based on retrospective cross-sectional studies and the diagnosis is commonly made on clinical grounds. An Italian multicenter study on 365 children with HT reported the occurrence of thyroid nodularity and cancer in 31% and 3% of the patients, respectively.[24] Kambalapalli et al.[27] found an equal incidence of thyroid nodules and DTC in thyroid peroxidase antibody (TPOAb)-positive and -negative patients.

HT is a frequent condition in children and adolescents, and therefore, a better understanding of the risk for developing cancer is of great importance. This retrospective study was designed to investigate the role of HT on the development of thyroid nodules and cancer in a large group of children and adolescents followed-up for up to 12 years.