Long-term ultrasound follow-up of intrathyroidal ectopic thymus in children.

OBJECTIVE: To present the sonographic follow-up of intrathyroidal ectopic thymus (IET) in children and adolescent patients. PATIENTS: Out of the 507 children referred to FNAB between 2006 and 2018, 30 (5.9%) pediatric patients (10 females), mean age 5.7 years (1.2-13.8, median 4.9 years) were diagnosed with IET. METHODS: A retrospective analysis of medical files of patients diagnosed with IET between 2006 and 2018. Assessed data included ultrasound characterisation, elastographic strain ratio (SR) results and hormonal evaluation. RESULTS: Analysis of thyroid US scans revealed that the mean age at the first thyroid ultrasound was 5.7 (1.2-13.8, median 4.9) years, and at the last US 10.7 (3.7-18, median 10.5) years. The mean time of the IET observation was 59.6 (2-148, median 53.5) months. On US, IET was hypoechoic with multiple linear and punctate echoes, hypovascular, fusiform on longitudinal plane and round or polygonal on an axial plane, more common in the right thyroid lobe (66.7%) and located in the posterior part of the lobes (54.5%), bilateral in two patients and multifocal in one patient. SR of IET was similar to the surrounding normal thyroid tissue. Complete regression of IET was observed in 12/30 patients after a mean time of 81.7 months (median 76.5), at the mean age of 13.7 (9.2-18, median 13.9) years. FNAB was performed in 10/30 and a hemithyroidectomy in 1/30 IET patients. In the FNAB (+) group, patients were younger (5.08 vs 6.08 years) and lesions were larger (0.12 ml vs 0.05 ml) than in the FNAB (-) group. All patients with IET were euthyroid with negative TPOAb and TgAb levels. CONCLUSION: The reproducibility of unique ultrasound features of IETs allows for safe long-term follow-up of these benign lesions in the majority of pediatric patients: not only monitoring the regression of IET but also screening towards the rare occurrence of a tumor arising from the IET.

Follow-up of parenchymal changes in the thyroid gland with diffuse autoimmune thyroiditis in children prior to the development of papillary thyroid carcinoma.

PURPOSE: To present the outcomes of ultrasound (US) follow-ups in children with autoimmune thyroid disease who did not have a thyroid nodule on admission but developed papillary thyroid carcinoma (PTC) and to characterize the parenchymal changes in the thyroid gland prior to the development of PTC. METHODS: A retrospective thyroid US scan review of 327 patients diagnosed with AIT was performed. Forty patients (40/327, 12.2%) presented nodular AIT variant with a normoechogenic background. Eleven patients (11/327, 3.4%, 11/40, 27.5%) presenting this variant were diagnosed with PTC (nine females-mean age 15.3 years; two males aged 11 and 13 years). In five of 11 patients, the suspicious nodule that was later confirmed to be PTC was detected on the initial US at presentation. For the remaining six females (6/11) who developed PTC during the follow-up, we retrospectively analysed their US thyroid scans and these patients were selected for analysis in this study. RESULTS: On admission, the US evaluation revealed an enlarged normoechogenic thyroid gland in three patients and a hypoechogenic thyroid gland with fibrosis as indicated by irregular, chaotic hyperechogenic layers in three patients. No thyroid nodules were identified. Ultrasound monitoring revealed increasing echogenicity of the thyroid parenchyma during the follow-up. PTC developed in a mean time of 4.6 years (1 9/12-7 4/12 years) since referral to the outpatient thyroid clinic and 2.9 years (6/12-6 9/12) since the last nodule-free US thyroid scan. CONCLUSIONS: Sonographic follow-up assessments warrant further exploration as a strategy to determine PTC susceptibility in the paediatric population.

Ultrasound variants of autoimmune thyroiditis in children and adolescents and their clinical implication in relation to papillary thyroid carcinoma development.

BACKGROUND: The prevalence of autoimmune thyroiditis (AIT) and papillary thyroid carcinoma (PTC) is rising in children and adolescents, and the coincidence of AIT and PTC is as high as 6.3-43%. OBJECTIVE: To investigate the ultrasound manifestation of AIT in relation to PTC development in paediatric patients. PATIENTS: 179 paediatric patients (133 females), mean (SD) age: 13.9 (3.03) years diagnosed with AIT and referred for ultrasound evaluation. Eight patients were diagnosed with PTC (6 females). METHODS: Retrospective analysis of thyroid ultrasound scans of patients diagnosed with AIT. Thyroid and autoimmune status was assessed based on TSH, fT4, fT3 and increased aTPO and/or aTG and/or TRAB levels. In patients with PTC, total thyroidectomy was performed. RESULTS: Analysis of thyroid US scans revealed that the following five ultrasound variants of AIT were observed in 179 patients: the most common in 35.2%-diffuse thyroiditis with hypoechogenic background and normoechogenic parenchyma, in 30.2%-diffuse thyroiditis with irregular background, in 18.9% nodular variant with normoechogenic background, in 11.7%-micronodulations and in 3.9%-diffuse hypoechogenic background. Eight cases of PTC were diagnosed in nodular variant of AIT with normoechogenic irregular background. CONCLUSION: Patients with AIT and nodular variant with normoechogenic irregular background of the thyroid gland on US scans are in the risk group of developing PTC and should be followed up with regular neck US assessment.

A novel insA2933 causes premature termination of translation and is accompanied by overexpression of truncated androgen receptor gene in a patient with complete androgen insensitivity syndrome.

A patient with a female phenotype, 46,XY karyotype, and a diagnosis of complete androgen insensitivity syndrome (CAIS) was examined. Her mother and three 46,XX sisters were also included in the study. Sequence analysis of the androgen receptor gene (AR) revealed a novel A2933 insertion that alters the Tyr codon to a termination codon (Y857X), resulting in a truncated form of the receptor. Computer simulation revealed major conformational changes in the hydrophobic pocket that accommodates the hormone. An insA2933 results in a truncated receptor incapable of binding the ligand and is responsible for the clinical symptoms of CAIS in the patient. The levels of the AR transcript in peripheral blood leukocytes were higher in the patient than in her heterozygous mother and her heterozygous sister, as well as in the two healthy sisters. It is hypothesized that elevated levels of the AR transcript in the patient might be caused by the inability of the truncated receptor to react with IFI-16, which functions in complex with AR to inhibit the expression of the AR gene.

Expression of the central obesity and Type 2 Diabetes mellitus genes is associated with insulin resistance in young obese children.

OBJECTIVES: The assessment of the health consequences associated with obesity in young children is challenging. The aims of this study were: (1) to compare insulin resistance indices derived from OGTT in obese patients and healthy control (2) to analyze central obesity and Type 2 Diabetes genes expression in obese children, with special attention to the youngest group (< 10 years old). PATIENTS AND METHODS: The study included 49 children with obesity (median age 13.5 years old), and 25 healthy peers. Biochemical blood tests and expression of 11 central obesity and 33 Type 2 Diabetes genes was assessed. RESULTS: A significant difference in insulin resistance between obese and non-obese adolescents was observed in all studied indices (mean values of the insulin levels: 24.9 vs. 9.71 mIU/L in T0, 128 vs. 54.7 mIU/L in T60 and 98.7 vs. 41.1 mIU/L in T120 respectively; AUC: 217 vs. 77.2 ng/ml*h, mean values of B% (state beta cell function), S% (insulin sensitivity), and IR were 255 (±97) vs. 135 (±37.8), 46.6 (±37.3) vs. 84.2 (±29.6) and 3 (±1.55) vs. 1.36 (±0,56); HIS, WBIS and ISIBel median 3.89, 44.7, 0.73 vs. 8.57, 110, 2.25. All comparisons differed significantly p<0.001). Moreover, insulin sensitivity was significantly better in the older obese group (>10 years old): median AUC 239 vs. 104 ng/ml*h, and HIS, WBIS and ISIBel 3.57, 38, 0.67 vs. 6.23, 75.6, 1.87 respectively in the obese older compared to the obese younger subgroup, p<0.05. The expression of 64% of the central obesity genes and 70% of Type 2 Diabetes genes was higher in the obese compared to control groups. The differences were more pronounced in the younger obese group. CONCLUSION: Insulin resistance may develop in early stage of childhood obesity and in very young children may be associated with higher expression of the central obesity and Type 2 Diabetes genes.

Insulin resistance in adolescents with Turner syndrome is comparable to obese peers, but the overall metabolic risk is lower due to unknown mechanism.

PURPOSE: An increased risk of insulin resistance, hypertension and liver dysfunction is related to obesity (Ob), but may be also present in normal-weight Turner syndrome (TS) patients. The aim of the study was to compare metabolic risk in adolescents with TS and Ob. METHODS: The study included 21 non-obese with TS (all receiving human recombinant growth hormone, 17/21 estrogen/estrogen-progesterone), and 21 age-matched Ob girls (mean age 13.9 years). Glucose and serum insulin levels were assessed fasting and in 120' of standard oral glucose tolerance test. Levels of triglycerides (TG), total cholesterol (TC), low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol, alanine aminotransferase (ALT), FGF19, FGF21 and FGF23 levels were measured fasting. RESULTS: Mean BMI SDS was significantly lower in TS patients (0.1 vs 4.8 SD, p < 0.001). The mean systolic and diastolic blood pressure was significantly lower in TS patients (102.6 vs 124.2 mmHg, p < 0.001 and 67.1 vs 76.5 mmHg, p = 0.02). There were no differences concerning mean fasting, and post-load glucose (4.5 vs 4.3, 5.1 vs 5.8 mmol/L), and insulin (14.97 vs 17.19 and 69.3 vs 98.78 µIU/mL) levels, HOMA-IR (3.02 vs 3.4), TC (4.05 vs 4.4 mmol/L), TG (1.25 vs 1.37 mmol/L), ALT (26.9 vs 28.3 IU/L), FGF19 (232.8 vs 182.7 pg/mL), and FGF23 (12.3 vs 17.5 pg/mL) levels. Mean LDL (2.05 vs 2.7 mmol/L, p = 0.003) and FGF21 (293.9 vs 514.7 pg/mL, p = 0.007) levels were significantly lower, and HDL (1.7 vs 1.2 mmol/L, p < 0.001) level higher in TS group. CONCLUSIONS: Insulin resistance in adolescents with TS on growth hormone treatment is comparable to Ob patients, but overall metabolic risk factors seem to be lower.

Associations between bone, fat tissue and metabolic control in children and adolescents with type 1 diabetes mellitus.

AIMS: To investigate the relationship between bone-derived osteocalcin (OC), osteoprotegerin (OPG), Receptor Activator of Nuclear Factor NF-ĸB ligand (RANKL), and fat tissue-derived leptin and adiponectin with a clinical outcome of type 1 diabetes mellitus (T1DM) in children and adolescents. METHODS: 78 patients (43 girls and 35 boys), aged 11.5±4.3 years with T1DM and 11 age- and BMI-matched controls were included into the study. Patients were divided into 3 groups according to HbA1c level, I - below 7% [53 mmol/mol], II - 7-9% [53-75 mmol/mol] and III - above 9% [75 mmol/mol]. Blood samples for biochemical measurements were drawn at 8.00 AM, when the patients were in a fasting state. HbA1c was measured by the standardized IFCC method. OC, OPG, RANKL, leptin and adiponectin were measured by ELISA. ANOVA, and multiple regression analysis were used for statistical analysis. RESULTS: Significant differences in leptin and osteocalcin levels between groups with different HbA1c values were observed (p=0.03, p=0.04). Multiple regression analysis adjusted for age showed that serum OC and leptin negatively correlated with HbA1c levels (r=-0.22, p=0.004 and r=-0.27, p=0.0001, respectively). In contrast, serum OPG correlated positively with HbA1c (r=0.26, p=0.02) as well as with adiponectin (r=0.26, p=0.02) and RANKL (r=0.27, p=0.02) levels. The correlation of OC with HbA1c was the strongest in group I - patients with good metabolic control of DM (r=-0.43, p=0.03). In that group, in multiple regression analysis adjusted for age and BMI leptin correlated positively with daily dose of insulin (r=0.52, r=0.009). In group II and III in multiple regression analysis adjusted for age and BMI OC correlated negatively with leptin (r=-0.37, p=0.01). CONCLUSIONS: Our data suggest significant relationships between bone, fat tissue and glucose metabolism in pediatric patients with T1DM. The results can confirm that poor metabolic control is associated with reduced bone formation. On the other hand fat and bone tissue can influence glucose metabolism, potentiality in insulin-dependent manner. From these data leptin or OC may be potentially used as additional therapeutic agents for T1DM.