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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.

BACKGROUND: Due to the lack of specific pediatric studies, no data are available about natural history of endogenous subclinical hyperthyroidism (SH) in childhood. AIMS: (a) To investigate for the first time the natural history of SH [suppressed thyrotropin (TSH) and normal free thyroxine free thyroxine (FT4) levels] when presenting as initial manifestation of Hashimoto's thyroiditis (HT) in childhood (group A); (b) to compare spontaneous evolution of HT-related SH with that observed in age-matched patients with HT-related frank hyperthyroidism (suppressed TSH and elevated FT4 levels), i.e., Hashitoxicosis Htx (group B). RESULTS: In the 11 patients of group A, TSH normalization spontaneously occurred 1-24 months after diagnosis, while in the 10 patients of group B it occurred 3-9 months after diagnosis, with no differences between the 2 groups in terms of time interval from entry to TSH normalization. In group A, this time interval was related to baseline thyroid peroxidase antibodies (r = 0.78, p = 0.04). During follow-up, eight patients of each group remained euthyroid, whereas two became hypothyroid (in both groups) and one developed Graves' disease (in group A). CONCLUSION: (a) HT should be included among the causes of endogenous SH in pediatric age; (b) in children with HT-related SH, spontaneous normalization of TSH levels occurs within the first 24 months after diagnosis, as well as in age-matched patients with Htx; (c) in both these conditions, a further deterioration of thyroid function might re-present in some patients during follow-up; (d) Ht-related SH and Htx might be possibly seen as different biochemical stages along the same continuum.

We investigated the association between MBL2 gene exon 1 functional polymorphisms and autoimmune thyroid disease (AITD) in 163 Brazilian patients (87 with Hashimoto thyroiditis, HT; 76 with Graves' disease) and 214 healthy controls. Individuals carrying MBL2 O allele are at higher risk of developing AITD (OR = 1.58, 95\% CI: 1.11-2.26; P-value = 0.009) and HT (OR = 1.67, 95\% CI: 1.09-2.55; P-value = 0.013) as suggesting a possible role for mannose-binding lectin in influencing disease susceptibility.

Objective: Intrathyroidal lymphoid infiltrate (TLI) may show qualitative and quantitative differences in Hashimoto thyroiditis (HT); thyroidal functional status (TFS) may differ among HT patients. The aim of this study has been to evaluate TLI in different TFS of HT. Methods: Flow-cytometry (FC) was applied to thyroidal fine-needle cytology samples (FNC) in 23 patients. TLI was analyzed using the following fluoresceinated antibodies: CD3, CD4, CD5, CD8, CD10, CD19, CD25, CD69, CD95 (FAS). TFS was determined by serum TSH, FT3, FT4 immunoassays, in specific clinical settings, to classify the patients as euthyroid (16) and hypothyroid (7). Pearson’s correlation coefficient was used to evaluate possible correlations between CD4/CD8 ratio, CD4+ CD25+ CD69-: regulatory T (Treg) cells proportion, CD95 expression and TFS. Results: B-lymphocytes (CD19+, CD10±, CD5-, CD3-) were present in 18 cases, T-lymphocytes (CD19-, CD10-, CD5+, CD3+) in all the cases. CD4/CD8≥2:1 ratio was observed in 16 euthyroid and 3 hypothyroid; CD4/CD8≤1:1 ratio in none of euthyroid and in 4 hypothyroid. CD4+ CD25+ CD69- Treg cells proportion was lower in hypothyroid than in the euthyroid patients; CD4+, CD25+, CD95(FAS)+ were mainly expressed in hypothyroidism. Statistical analysis did not demonstrate associations among CD4/CD8 ratios, Treg cells proportions and CD95 expression in the two TFS. Conclusions: FNC may be used to assess TLI in HT. Intrathyroidal CD4/CD8 ≤ 1:1 ratio, CD4+, CD25+, CD69- cells reduction and CD95(FAS)+ are expression of Treg cells apoptosis and might be related to intense thyroidal damage and risk of hypothyroidism. Further studies are needed to assess their possible prognostic significance.