Studies of Dyshormonogenesis of Thyroid Gland in Taiwanese

• Main Authors: Dau-Ming Niu, 牛道明
• Other Authors: Ching-Yuang Lin
• Format: Others
• Language: zh-TW
• Published: 2004
• Online Access: http://ndltd.ncl.edu.tw/handle/02009671348613802287

博士 === 國立陽明大學 === 臨床醫學研究所 === 92 === The mutation of the thyroid peroxidase (TPO) gene that causes total iodide organification defect (TIOD) is a common and severe condition leading to dyshormonogenesis of the thyroid gland in Caucasians. However, the role of TIOD in Chinese patients with thyroid dyshormonogenesis is unknown. In this study, we followed 16 patients from 16 unrelated families in Taiwan and performed perchlorate discharge examination. Seven patients were found to have TIOD. These 7 patients underwent screening in search of TPO gene mutations. Three mutations (2268 insT, 2243 delT and G157C) were detected in 7 patients. The 2268 insT mutation was noted to be the most common among these TIOD patients (12 out of 14 studied alleles, 86%). With three intragenic polymorphic markers, we found that the alleles carrying the 2268insT mutation in Taiwan Chinese TIOD patients were tightly linked to a specific haplotype. This indicates that this common mutation among Taiwanese patients with TIOD is due to a founder effect. Besides the permanent form of CH, neonatal transient hypothyroidism (NTH) is frequently being detected by most confirmatory specilalised centres since the introduction of systematic screening of new-borns. The causes of NTH remain incompletely understood. Whether NTH is influenced by the genetic background is rarely discussed and remains unproven. Because the high incidence of 2268 insT mutation in our TIOD patients, we sought to determine whether the presence of this common mutation is associated with NTH in Taiwan. In the second study, a pair of mismatched primers was designed and used for this specific 2268insT mutation to screen 1000 normal babies and 260 babies with NTH. The carrier rate of 2268 insT in normal babies (1/200) was significantly lower than in babies with NTH (1/13; p<0.0001). Our observations strongly suggest that the presence of this TPO mutation contributes to the development of NTH. In third study, we use bone maturation to evaluate its contribution in the diagnosis of NTH versus dyshormonogenetic congenital hypothyroidism (DCH) in full-term newborns, and we also use bone maturation to test the hypothesis that NTH is perinatal in onset. This study included 20 patients with DCH and 43 with NTH. Thyroid function and measurements of the distal femoral epiphysis area (DFEA), obtained at the time of first confirmatory diagnosis, were compared between the two groups. The epiphysis area in two control groups with normal thyroid function was also measured and compared with that in patients with NTH, at age 1-3 days (control A), or at the age when normal thyroid function was confirmed (control B). And then, we found that mean DFEA was 0.04 cm2 in patients with DCH versus 0.22 cm2 in patients with NTH (P < 0.0001). An area < 0.05 cm2 was limited to patients with DCH. Conversely, a normal area (> 0.2 cm2) was only observed in patients with NTH. Mean epiphysis areas in control A (0.20 cm2) and in patients with NTH were similar (P = 0.37), consistent with perinatal onset of NTH. DEFA in control B (0.31 cm2) was significantly greater than in patients with NTH (P <0.01). It suggests that a short duration of hypothyroidism can significantly delay bone maturation. Finally, we conclude that examination of bone maturation at initial confirmatory evaluation yields important information pertaining to congenital hypothyroidism, not only to predict intellectual development, but also evaluate the risk of DCH.