Juvenilní Gravesova-Basedowova choroba(Prospektivní multicentrická studie v České republice)

Juvenile Graves-Basedow’s Disease(Multicentric Prospective Study in the Czech Republic)

Juvenile Graves-Basedow’s disease (GB) has so far no unified and rationalised diagnostic and therapeuticguidelines, 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 byspecialists from ESPE and ETA. This protocol was followed in the present study which summarises the results inthe Czech Republic.Twenty new patients (17 girls 13 ± 3 years old and 3 boys aged 15 ± 1 years) were examined, treated and followedup for 1.5 to 2.5 years in five clinics in the Czech Republic since 1996. None of these patients had iodine tabletprophylaxis. A sthenic form of GB was present in four patients out of 20, 13 exhibited mild ophthalmologicalsymptoms, and in 15 patients goitre was found by palpation and sonography. High levels of T4 (mean values of fT4were 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-abwere higher in 13 patients (457.10 ± 151.50 U/ml). Treatment was started in all patients with Carimazol in a doseof 0.5 mg/kg/day (in three daily doses), with the exception of one patient who received Propycil for a short periodof time. L-Thyroxin (50 mg/day) was supplemented after one month’s treatment in 9 patients. During theexamination, 17 patients received Trimepranol (30 mg/day) and this was then discontinued. One girl did notrespond sufficiently to the therapy, hence total thyroidectomy was performed around 9 months after startingtherapy. Another two girls underwent this surgical operation because of a relapse of the disease and lack ofco-operation after 11 and 12 months of conservative treatment, respectively. Relapses of GB symptoms werealtogether noted in 6/19 patients (cca 35 %) after 11 to 30 months of conservative therapy. No differences werefound between treatment with Carbimazol combined with L-Thyroxin as compared with Carbimazol only. Thelevels of fT4 returned to normal after 2 - 4 weeks of treatment, sTSH-ab after 4 - 7 weeks, T3 after 3 - 6 monthsand rTSH-ab after 12 - 18 months. The titres of TPO-ab did not change and those of hTg-ab decreased to 50 % inthe 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 followedand these alleles were more frequently found in juvenile GB, as compared with control healthy children. Besidesthe HLA loci, we tested the non-HLA locus CTLA-4 gene on chromosome 2q33 as one of the possible factors (besidesCD28) affecting autoimmunological susceptibility for GB. However, this was not confirmed in our study, possiblybecause 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 detailedfamily-history, include also a routine examination of sTSH, fT4 and/or T3, rTSH-ab, ultrasonic examination of thethyroid gland, where relapses are more likely to occur in large, diffuse goitres. Molecular genetic examinations arerather expensive and are at present in the experimental stages. Therapy of juvenile GB should start withthyreostatics, preferably with Carbimazol (since it has fewer side-effects than Propycil) in an initial dose of 0.5mg/day. Patients should be warned about the possibility of complicating side-effects (especially symptoms of skinand oral epithelium irritation, where therapy should be interrupted immediately), but which do not requireperiodical examinations of the white blood count. Conservative therapy should not last longer than 2 years. Ifrelapses 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 oftherapeutic 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-hygienicregulations.The follow-up of our 20 patients will continue for another three years.

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