Investigation of the concomitant peripheral resistance and thyroid hormone receptor gene analysis in cases with central thyroid hormone resistance

This trial was designed to assess the concomitant peripheral resistance in pediatric cases, who were considered to have pituitary thyroid hormone (TH) resistance and exhibited indistinguishable clinical results and determine the incidence of TRβ mutation in the "investigational group". 20 patients, including 13 cases with thyroid gland dysgenesis, monitored with the diagnosis of pituitary TH resistance, in whom TSH level could not be suppressed during monitoring despite an adequate dose of L-T4 administered, were included in the trial (13 girls, mean age: 7.03±2.72 years). TH peripheral effects were assessed before and after L-T3 administration using sT4, TSH, SHBG, total cholesterol, ALP, osteocalcin, ACE levels and CPK, M-mod and Doppler ECHO investigations and TH β receptor (TRβ) gene analyses were performed. The comparison of the pre-L-T3 and post-L-T3 biochemical measurements revealed a significant increase in SHBG, osteocalcin and ACE levels and a significant reduction in total cholesterol and CPK levels (p<0.001). No difference was detected in ALP and cardiac parameters. TRβ gene analysis revealed homozygote and heterozygote rs3752874 changes in 2 and 4 patients respectively, and homozygote and heterozygote IVS8 -110 G>A changes in 2 and 7 patients, respectively. Achievement of various degrees of peripheral tissue response to supraphysiological L-T3 concentrations indicates that the response to high T3 levels is maintained and the SHBG and CPK changes exhibiting the highest responses may be guiding. The two changes detected in the TRβ gene analysis were considered not to be involved in the pathogenesis of resistance. While the number of cases is not adequate, we may suggest that TRβ gene mutation is not frequent among patients similar to those in our investigational group. However, this doesn't mean that all the TH modes of action are functional. In patients with congenital hypothyroidism, who sustain high levels of TSH despite meeting adequate therapeutic criteria, the condition may be attributed to a functional defect in the intrauterine growth process of the hypothalamicpituitary- thyroid axis rather than a concomitant genetic abnormality.