Graves’s disease is the most common type of autoimmune hyperthyroidism. Numerous studies indicate different factors contributing to the onset of the disease. Despite years of research, the exact pathomechanism of Graves’ disease still remains unresolved, especially in the context of immune response. B cells can play a dual role in autoimmune reactions, on the one hand, as a source of autoantibody mainly targeted in the thyroid hormone receptor (TSHR) and, on the other, by suppressing the activity of proinflammatory cells (as regulatory B cells). To date, data on the contribution of Bregs in Graves’ pathomechanism, especially in children, are scarce. Here, we investigated the frequencies of Bregs before and during a methimazole therapy approach. We reported higher Foxp3+ and IL-10+ Breg levels with CD38- phenotype and reduced numbers of CD38 + Foxp3 + IL-10+ in pediatric Graves’ patients. In addition, selected Breg subsets were found to correlate with TSH and TRAb levels significantly. Noteworthy, certain subpopulations of Bregs were demonstrated as prognostic factors for methimazole therapy outcome. Our data demonstrate the crucial role of Bregs and their potential use as a biomarker in Graves’ disease management.

The risk of malignancy in thyroid nodules correlates with the presence of ultrasonographic features. In adults, ultrasound risk-classification systems have been proposed to indicate the need for further invasive diagnosis. Furthermore, elastography has been shown to support differential diagnosis of thyroid nodules. The purpose of our study was to assess the application of the American Thyroid Association (ATA), British Thyroid Association (BTA) ultrasound risk-classification systems and strain elastography in the management of thyroid nodules in children and adolescents from one center. Seventeen nodules with Bethesda III, IV, V and VI were selected from 165 focal lesions in children. All patients underwent ultrasonography and elastography followed by fine needle aspiration biopsy. Ultrasonographic features according to the ATA and BTA stratification systems were assessed retrospectively. The strain ratio in the group of thyroid nodules diagnosed as malignant was significantly higher than in benign nodules (6.07 vs. 3.09, p = 0.036). According to the ATA guidelines, 100% of malignant nodules were classified as high suspicion and 73% of benign nodules were assessed as low suspicion. Using the BTA U-score classification, 80% of malignant nodules were classified as cancerous (U5) and 20% as suspicious for malignancy (U4). Among benign nodules, 82% were classified as indeterminate or equivocal (U3) and 9% as benign (U2). Our results suggest that application of the ATA or BTA stratification system and elastography may be a suitable method for assessing the level of suspected malignancy in thyroid nodules in children and help make a clinical decision about the need for further invasive diagnosis of thyroid nodules in children.

Pathway involving insulin-like growth factor 1 (IGF-1) plays significant role in growth and development. Crucial role of IGF-1 was discovered inter alia through studies involving deficient patients with short stature, including Laron syndrome individuals. Noteworthy, despite disturbances in proper growth, elevated values for selected stem cell populations were found in IGF-1 deficient patients. Therefore, here we focused on investigating role of these cells—very small embryonic-like (VSEL) and hematopoietic stem cells (HSC), in the pathology. For the first time we performed long-term observation of these populations in response to rhIGF-1 (mecasermin) therapy. Enrolled pediatric subjects with IGF-1 deficiency syndrome were monitored for 4–5 years of rhIGF-1 treatment. Selected stem cells were analyzed in peripheral blood flow cytometrically, together with chemoattractant SDF-1 using immunoenzymatic method. Patients’ data were collected for correlation of experimental results with clinical outcome. IGF-1 deficient patients were found to demonstrate initially higher levels of VSEL and HSC compared to healthy controls, with their gradual decrease in response to therapy. These changes were significantly associated with SDF-1 plasma levels. Correlations of VSEL and HSC were also reported in reference to growth-related parameters, and IGF-1 and IGFBP3 values. Noteworthy, rhIGF-1 was shown to efficiently induce development of Laron patients achieving at least proper rate of growth (compared to healthy group) in 80% of subjects. In conclusion, here we provided novel insight into stem cells participation in IGF-1 deficiency in patients. Thus, we demonstrated basis for future studies in context of stem cells and IGF-1 role in growth disturbances. Graphical abstract

There are data indicating the coexistence of papillary thyroid carcinoma and autoimmune thyroiditis (AIT) in children. The aim of the study was elastographic evaluation of thyroid nodules in children and adolescents with AIT and nodular goiter in relation to cytological and/or histopathological diagnosis. We examined 215 children (57 boys and 158 girls) with 261 thyroid nodules (143 non-AIT and 118 AIT). All study participants underwent a conventional ultrasound examination with elastography followed by fine needle aspiration biopsy (FNAB). Abnormal Strain Ratio (SR ≥ 5) was observed in 36 non-AIT nodules and 15 AIT nodules. Papillary thyroid carcinoma was diagnosed in 5 patients (2% of all investigated nodules). SR of malignant thyroid nodules was statistically higher in comparison to SR of benign nodules both in the group of non-AIT (6 ± 4 vs. 3.67 ± 2.62, p = 0.024) and AIT nodules (6.3 ± 0.01 vs. 2.92 ± 1.89, p = 0.047). Comparison of non-AIT and AIT benign nodules revealed that SR was higher in non-AIT nodules (3.67 ± 2.62 vs. 2.92 ± 1.89, p = 0.01). We observed a strong positive correlation (R = 1) between TSH concentration and SR ratio in the group of all malignant thyroid nodules. Autoimmune inflammatory process of the thyroid gland does not limit the use of elastography in the diagnosis of thyroid nodules in children.

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