Juvenile Graves-Basedow’s disease (GB) has so far no unified and rationalised diagnostic and therapeutic guidelines, as was evident from the results of the European Questionnaire in 1992 - 1993. For this reason, a European Multicentric Study of juvenile GB was recommended in 1995 according to a protocol prepared by specialists from ESPE and ETA. This protocol was followed in the present study which summarises the results in the Czech Republic. Twenty new patients (17 girls 13 ± 3 years old and 3 boys aged 15 ± 1 years) were examined, treated and followed up for 1.5 to 2.5 years in five clinics in the Czech Republic since 1996. None of these patients had iodine tablet prophylaxis. A sthenic form of GB was present in four patients out of 20, 13 exhibited mild ophthalmological symptoms, and in 15 patients goitre was found by palpation and sonography. High levels of T4 (mean values of fT4 were 81.80 ± 7.70 pmol/l) and T3 (means 8.40 ± 0.84 nmol/l) with reduced levels of sTSH (mean 0.008 ± 0.003 mU/l) were encountered in all patients. The titres of rTSH-ab were significantly higher in 17 patients (means 109.50 ± 15.81 U/ml, while TPO-ab were significantly increased in 14 patients (means 457.20 ± 130.72 U/ml) and hTg-ab were higher in 13 patients (457.10 ± 151.50 U/ml). Treatment was started in all patients with Carimazol in a dose of 0.5 mg/kg/day (in three daily doses), with the exception of one patient who received Propycil for a short period of time. L-Thyroxin (50 mg/day) was supplemented after one month’s treatment in 9 patients. During the examination, 17 patients received Trimepranol (30 mg/day) and this was then discontinued. One girl did not respond sufficiently to the therapy, hence total thyroidectomy was performed around 9 months after starting therapy. Another two girls underwent this surgical operation because of a relapse of the disease and lack of co-operation after 11 and 12 months of conservative treatment, respectively. Relapses of GB symptoms were altogether noted in 6/19 patients (cca 35 %) after 11 to 30 months of conservative therapy. No differences were found between treatment with Carbimazol combined with L-Thyroxin as compared with Carbimazol only. The levels of fT4 returned to normal after 2 - 4 weeks of treatment, sTSH-ab after 4 - 7 weeks, T3 after 3 - 6 months and rTSH-ab after 12 - 18 months. The titres of TPO-ab did not change and those of hTg-ab decreased to 50 % in the course of 12 months, but their values remained slightly higher. Thyroid diseases were reported in the family-history of 11/20 patients, namely in six mothers with hyperthy- roidism. In the molecular genetic study, the HLA class II (HLA-DRB3, HLA-DQA1, HLA-DQB1) was followed and these alleles were more frequently found in juvenile GB, as compared with control healthy children. Besides the HLA loci, we tested the non-HLA locus CTLA-4 gene on chromosome 2q33 as one of the possible factors (besides CD28) affecting autoimmunological susceptibility for GB. However, this was not confirmed in our study, possibly because of the small number of patients. Mutations of the TSH receptor gene were not found in our 20 probands. It may be concluded that the diagnostic procedure and also the follow-up of patients should, besides a detailed family-history, include also a routine examination of sTSH, fT4 and/or T3, rTSH-ab, ultrasonic examination of the thyroid gland, where relapses are more likely to occur in large, diffuse goitres. Molecular genetic examinations are rather expensive and are at present in the experimental stages. Therapy of juvenile GB should start with thyreostatics, preferably with Carbimazol (since it has fewer side-effects than Propycil) in an initial dose of 0.5 mg/day. Patients should be warned about the possibility of complicating side-effects (especially symptoms of skin and oral epithelium irritation, where therapy should be interrupted immediately), but which do not require periodical examinations of the white blood count. Conservative therapy should not last longer than 2 years. If relapses occur repeatedly, definitive treatment should, according to our opinion, comprise total thyroidectomy (23, 26) after attaining the euthyroid state, and performed by a surgeon experienced in thyroid surgery. The use of therapeutic radioiodine is strongly recommended in the USA (5) and is being introduced in Western Europe (10). However, it is not possible to prescribe it for cases of juvenile GB in the CR because of local radio-hygienic regulations. The follow-up of our 20 patients will continue for another three years.

        Key words: juvenile Graves’ disease, multicentric study, diagnosis, treatment, genetics