Autoimmune Thyroiditis and Risk of Malignancy in Children with Thyroid Nodules

Keefe, Gregory P.; Culbreath, Katherine; Cherella, Christine E; Smith, Jessica R.; Zendejas-Mummert, Benjamin; Shamberger, Robert C.; Richman, Danielle M; Hollowell, Monica; Modi, Biren P.; Wassner, Ari J.

doi:10.1089/thy.2022.0241

Cited by 13 publications

(14 citation statements)

References 39 publications

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“…The almost 50% of coincidence of AIT and PTC in our study is concordant with two-fold increase in thyroid cancer risk in AIT paediatric patients presented in recent studies ( 67 , 68 ). Similar to other studies, although AIT is associated with an increased risk of thyroid cancer, we did not find an association between AIT and the thyroid cancer stage at diagnosis ( 67 ). We believe that this could also be the effect of age and puberty on the different biological spectra of PTC in children, as suggested by He et al.…”

Section: Discussionsupporting

confidence: 92%

Ultrasound, laboratory and histopathological insights in diagnosing papillary thyroid carcinoma in a paediatric population: a single centre follow-up study between 2000-2022

et al. 2023

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BackgroundPapillary thyroid carcinoma (PTC) often coincides with autoimmune thyroiditis (AIT); whether this association is incidental or causal remains debated.ObjectiveTo evaluate the ultrasonographic, laboratory, and histopathological features of PTC in paediatric patients with and without AIT and its relationship to puberty.DesignA retrospective cohort study.Patients and methodsA retrospective analysis of medical records of 90 patients (69; 76.7% females). The mean age at PTC diagnosis was 13.8 years [range 6-18]. All patients were evaluated ultrasonographically before thyroid surgery. Thyroid nodules were categorised using the European Thyroid Imaging Reporting and Data System (EU-TIRADS PL), and cytopathology was assessed using Bethesda criteria. Neck ultrasound results and thyroid and autoimmune status were correlated with histopathological PTC assessment.ResultsThe coexistence of PTC and AIT was found in 48.9% (44/90) of patients. The percentage of AIT was increasing with age; AIT was present only in 1/3 of prepubertal, close to 50% in pubertal, and over 60% in adolescent patients. The youngest patients (aged <10 years old) presented more often with goitre and lymphadenopathy and less often with AIT than adolescents (15-18 years of age). There were no differences in TPOAb, TgAb, and TSH levels between the age subgroups. Presurgical TgAb levels were higher than those of TPOAb in the youngest patients. Histopathological analysis revealed that the solid subtype was observed more often in prepubertal children and diffuse sclerosing in children below 14 years of age, whereas the classic subtype dominated in late pubertal. Univariate and multivariate analyses revealed that lymph nodes metastases (LNM) were associated with PTC diameter and fT4 level, whereas extrathyroidal extension with age and angioinvasion with PTC diameter and age. The correlations between age and fibrosis, and the presence of psammoma bodies in malignant tissues were close to significant. We did not observe an association between TSH levels and the presence of autoimmunity and PTC variables.ConclusionsIn paediatric patients the natural course of PTC may be less aggressive in adolescent patients than in younger children (especially < 10 years of age). We suggest that pre-operative evaluation of paediatric patients with thyroid nodules could include apart from assessment of thyroid hormones, evaluation of TPOAb, TgAb, and TRAb together with comprehensive neck ultrasonography.

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Section: Discussionsupporting

confidence: 92%

Ultrasound, laboratory and histopathological insights in diagnosing papillary thyroid carcinoma in a paediatric population: a single centre follow-up study between 2000-2022

et al. 2023

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“…In our study, however, we found that AIT was observed in 50% of operated children, but we could not confirm the association of AIT with the PTC stage in relation to LNM or ETE. The only association involving the extent of the disease was found in relation to the age, tumour diameter, and TPOAb, similarly as observed in other recent paediatric studies ( 59 – 61 ). In paediatric patients, Huang et al.…”

Section: Discussionsupporting

confidence: 89%

Ultrasound evolution of parenchymal changes in the thyroid gland with autoimmune thyroiditis in children prior to the development of papillary thyroid carcinoma – a follow-up study

et al. 2023

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BackgroundFollicular cell-derived thyroid carcinoma represents the vast majority of paediatric thyroid cancers (TCs). Papillary thyroid carcinoma (PTC) accounts for over 90% of all childhood TC cases, and its incidence in paediatric patients is increasing. The objective of this follow-up study was to present the outcome of ultrasound (US) and laboratory monitoring of paediatric patients with autoimmune thyroiditis (AIT) prior to the development of PTC.Patients and methodsThis prospective study included 180 children and adolescents (132 females; 73.3%) with a suspicion of thyroid disorder referred to the Outpatient Endocrine Department. The patients were divided into four groups: 1) 28 patients with a mean age of 10.7 [standard deviation (SD), 3.1] y, in whom PTC was detected during the active surveillance of AIT [AIT(+), PTC(+) follow up (F)]; 2) 18 patients with a mean age of 12.8 (SD, 3.4) y, in whom PTC and AIT were detected upon admission (A) [AIT(+), PTC(+) A]; 3) 45 patients with a mean age of 13.0 (SD, 3.4) y, in whom PTC was detected upon admission and AIT was excluded [AIT(-), PTC(+) A]; and 4) an age- and sex-matched control group of 89 patients with AIT and with a mean age of 9.4 (SD, 3.0) y. The analysis included clinical, US, and laboratory assessment results of children on admission (groups 1–4) and during follow-up (groups 1 and 4) in the Paediatric Endocrine Outpatient Department.ResultsUpon admission of those in group 1, the US evaluation revealed a hypoechogenic thyroid gland in 12 and an irregular normoechogenic gland in 16 patients. US monitoring revealed an increase in thyroid echogenicity and an increased irregularity of the thyroid structure during the follow-up period of all of the patients from group 1. Such changes were not noticed in group 4. PTC was diagnosed at the mean time of 3.6 y (3 mo–9 y) since AIT confirmation in group 1. The mean maximum PTC diameter as per the US was significantly smaller in group 1 than in groups 2 and 3 [13.2 (10.8) mm vs. 22.2 (12.8) and 22.05 (15.4) mm]. Fewer patients in group 1 were referred to 131I than in groups 2 and 3 (71.4% vs. 94.4 and 93.3%). Interestingly, significant differences were observed in the thyroglobulin antibody (TgAb)/thyroid peroxidase antibody (TPOAb) ratio between groups 2 and 3, as opposed to group 4, at the beginning of observation [15.3 (27.6) and 3.5 (8.8] vs. 0.77 (1.9)]. In group 1, after the follow-up, an increase in the TgAb/TPOAb ratio was observed [1.2 (9.8) to 5.2 (13.5)]. There were no significant differences between groups 1–3 in labeling index Ki67, lymph nodes metastasis, extrathyroidal extension, and angioinvasion. There were no associations between thyroid-stimulating hormone, TgAb, and the extent of the disease.ConclusionThe use of thyroid US focused on the search for developing tumours in the routine follow-up of patients with AIT may not only help in the early detection of thyroid malignancies that are not clinically apparent but may also influence the invasiveness of oncological therapy and reduce the future side effects of 131I therapy. We propose that the repeat evaluation of TPOAb and TgAb warrants further exploration as a strategy to determine TC susceptibility in paediatric patients with AIT in larger multicentre studies.

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“…The most frequently reported risk factors are underlying thyroid disease, previous head and neck irradiation, chemotherapy, predisposing genetic mutations and family history (3)(4)(5)(6)(7)(8)(9)(10). Based on these data, the most frequent risk factor observed in our cohort was autoimmune thyroiditis, followed by previous treatment for childhood cancer.…”

Section: Discussionmentioning

confidence: 64%

“…Fine-needle agobiopsy (FNAB) for cytological category determination is required when nodule size is greater than 1 cm or suspicious features of malignancy are present. Lymph node involvement, intra-nodal calci cations or vascularization, hypoechogenic pattern, "larger than taller" shape, margins unde ned, right lobe localization, and upper normal range/high Thyroid Stimulation Hormone (TSH) levels have been considered predictive of malignancy (3)(4)(5)(6)(7)(8)(9)(10). Previous radiation exposure or cancer treatment, underlying thyroid disease, family history for thyroid cancer and predisposing genetic mutations represents known risk factors for thyroid cancer (1).…”

Section: Introductionmentioning

confidence: 99%

Clinical features of thyroid cancer in paediatric age. Experience of a tertiary centre in the 2000–2020 period

et al. 2023

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Purpose. To describe the clinical features of a paediatric cohort affected by differentiated thyroid cancer (DTC) followed in a tertiary Department of Paediatric Endocrinology.Methods. Clinical data of 41 patients affected by DTC in the 2000-2020 period were reviewed.Results. The main risk factor was autoimmune thyroiditis (39%). Cytological categories were TIR3b in 39%, TIR4 in 9.8%, TIR5 in 51.2%. After total thyroidectomy, radioiodine treatment was performed in 38 subjects (92.7%). ATA low-risk category was assigned in 11 (30.5%), intermediate-risk category in 15 (41.7%), and high-risk category in 10 patients (27.8%). Age at diagnosis was 15.1 ± 0.92 years in low-risk category, 14.7 ± 0.59 in intermediate-risk category, 11.7 ± 0.89 years in high-risk category (p=0.01). TIR3b was manly observed in low-risk class (63.6%), while TIR5 was mainly reported in intermediate and highrisk class (60% and 80% respectively) (p= 0.04). Post-surgery stimulated thyroglobulin was increased in high-risk class (407.8±307.1 ng/ml) [p=0.04]. Tumour size was larger in high-risk category (42.6 ± 2.6 mm), than in low and intermediate-risk categories (19.4 ± 3.5 mm and 28.5 ± 3.9 mm, respectively) (p=0.008). Patients in intermediate and high-risk categories displayed more tumour multifocality (60% and 90% respectively) (p < 0.005). Disease relapse was mainly observed in high risk category (40%, p=0.04). Conclusion. DTC in childhood is more aggressive than in adults, but the overall survival rate is excellent. The therapeutic approach is still heterogeneous, especially in low-risk category. Further studies are needed to standardize management and reduce disease persistence in childhood.

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Autoimmune Thyroiditis and Risk of Malignancy in Children with Thyroid Nodules

Cited by 13 publications

References 39 publications

Ultrasound, laboratory and histopathological insights in diagnosing papillary thyroid carcinoma in a paediatric population: a single centre follow-up study between 2000-2022

Ultrasound, laboratory and histopathological insights in diagnosing papillary thyroid carcinoma in a paediatric population: a single centre follow-up study between 2000-2022

Ultrasound evolution of parenchymal changes in the thyroid gland with autoimmune thyroiditis in children prior to the development of papillary thyroid carcinoma – a follow-up study

Clinical features of thyroid cancer in paediatric age. Experience of a tertiary centre in the 2000–2020 period

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