The retrospective study included children who were newly diagnosed with GD between 2014 to 2018 at our Pediatric Department. The including criteria were as follows: the diagnosis of GD was based on clinical and biochemical findings, such as palpitations, fatigue, irritability, increased appetite, weight loss, diarrhoea, increased perspiration, elevated serum free thyroxine (FT4) and free triiodothyronine (FT3) levels, suppressed serum thyrotropin (TSH) level, and positive TRAb; the presence of bilateral exophthalmos according to the reference . Children with peptic ulcers, severe hypertension, cardiovascular diseases, liver dysfunction, tumor, diabetic mellitus, infectious diseases, and other autoimmune diseases were excluded. We also excluded children who had received previous ATD treatment at baseline, and those who were lost to follow-up during the study. A total of 40 children fulfilled the criteria. Of these, 20 children were treated by intravenous MPT followed by oral prednisolone administration and ATD treatment, aged 7.7±3.2 (range 2.0-14.0) years, 6 boys and 14 girls, 20 children were treated with ATD alone (n=20), aged 8.9±4.0 (range 2.0-14.0) years, 4 boys and 16 girls. The control group and the pulse group had similar age and sex distribution.
We obtained clinical and treatment data from children’s medical records. Age, sex, clinical signs, goiter size, serum concentrations of FT3, FT4, TSH, thyroid peroxidase antibodies (TPOAb), thyroglobulin antibodies (TGAb), and TRAb, electrocardiogram (ECG), and thyroid and cardiac ultrasound were recorded at diagnosis and during follow-up. Follow-up visits occurred 10 days, 30days, and 60 days after treatment.
All children received ATD treatment (methimazole 1.0mg/kg/day) after diagnosis. The doses of methimazole were adjusted according to individual’s weight and thyroid hormone levels. Metoprolol (0.5-1.0mg/kg/day) was administered orally if heart rate exceeds 100 bpm . In the pulse group, high-dose methylprednisolone was infused intravenously at a dose of 5mg/kg/day for 3 successive days, and the dosage was reduced by half every 3 days. Blood pressure, blood glucose, and electrocardiogram were monitored daily. After 3 cycles of this course, oral prednisolone was administered. The dosage of prednisolone was gradually tapered off over a period of 3 weeks. Oral calcium and vitamin-D were also supplemented for children during glucocorticoid treatment.
The study was approved by the Ethics Committee of Linyi People’s Hospital (approval number: YX10070). Written informed consents for anonymized data to be collated and analyzed were obtained from all patients’ parents.
Fasting serum samples were collected in the morning from all subjects. Serum FT3, FT4, TSH, TPOAb, TGAb, and TRAb concentrations were measured by an automated chemiluminescence immunoassay system (Advia Center, Siemens, Munich, Germany). Normal ranges were 2.27-4.22 pg/mL for FT3, 0.88-1.75 ng/dL for FT4, 0.35-5.5 μIU/mL for TSH, 0-60 IU/mL for TPOAb, 0-60 IU/mL for TGAb, and 0-1.22 IU/L for TRAb. TPOAb, TGAb, and TRAb values above the normal ranges were defined as positive. The intra- and inter-assay coefficients of variation were all <5.0% and <4.0%, respectively. The sensitivity of FT3, FT4, TSH, TPOAb, TGAb, and TRAb were 0.19 pg/mL, 0.1 ng/dL, 0.001 μIU/mL, 0.1 IU/mL, 10 IU/mL, and 0.01 IU/L respectively.
Grading of goiter was performed by inspection and palpation, and was classified according to the World Health Organization (WHO) criteria: grade 0, no goiter; grade 1,goiter palpable but not visible; grade 2, goiter visible with neck in normal position . Degree of proptosis was measured with a Hertel exophthalmometer. Physical examination of all subjects was done by one experienced investigator.
Thyroid ultrasound was performed with a 5-12 MHz linear-array transducer on a LOGIQ 9 scanner (GE Medical Systems, Milwaukee, WI, USA). Echocardiography was performed with a 2-5 MHz transducer using an IU-22 ultrasound scanner (Philips Medical System, Bothell, WA, USA). All ultrasound examinations were carried out by the same trained sonographer. ECG was recorded with an electrocardiograph (1550p; Nihon Kohden, Tokyo, Japan) at paper speed of 25 mm/s and 10 mv/mm.
Normal distribution of variables was checked with the Shapiro-Wilk test before further analyses. Values of FT3, FT4, and TRAb showed Normal distributions. Values of TSH, TPOAb, and TGAb showed skewed distributions. Therefore, normally distributed variables were expressed as mean ± standard deviation, and skewed distributed data were expressed as the median and interquartile range. Chi-square test was used to compare clinical characteristics of the two groups. Repeated measures general linear models were used to determine whether there were changes in values of FT3, FT4, and TRAb at baseline, 10 days, 30days, and 60 days. Friedman’s nonparametric test was used to analyze changes in TSH, TPOAb, and TGAb levels at different time points. The Mann-Whitney U test was used to compare nonparametric data at each moment between groups. A two-tailed P-value of less than 0.05 was considered statistically significant. The analyses were performed using statistical software SPSS version 19.0 (SPSS Inc. Chicago, USA).