• Biomedical Science Letters
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• v.5 no.1
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• pp.11-15
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• 1999

Thyroxine (3,5,3',5'-L-tetraiodothyronine; T$_4$) is the most commonly measured thyroid hermono for the diagnosis of various thyroid disorders. Although radioimmunoassay (RIA) is still considered as the reference technique for the measurement of T$_4$, it is generally regarded that RIA has its primary disadventages in handling the wastes and controling the human and material resources. Therefore, establishment of enzyme-linked immunosorbent assay (ELISA) has of great significance. To verify the usefulness of our enzyme immunoassay, we have obtained the standard dose response curve of T$_4$ in patient's sera which is inversely proportional to the amount of herseradish peroxidase (HRP) conjugated monoclonal antibody of T$_4$ bound to the wells. The correlation coefficient (r) between the ELISA and chemiluminescent assay was 0.444 (n=38). Thus we have investigated the establishment of rapid and sensitive competitive ELISA assay method for detection of T$_4$ in patient's sera.

• Genomics & Informatics
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• v.19 no.3
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• pp.29.1-29.10
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• 2021

In our previous studies, we have demonstrated the association of certain variants of the thyroid-stimulating hormone receptor (TSHR), thyroid peroxidase (TPO), and thyroglobulin (TG) genes with congenital hypothyroidism. Herein, we explored the mechanistic basis for this association using different in silico tools. The mRNA 3'-untranslated region (3'-UTR) plays key roles in gene expression at the post-transcriptional level. In TSHR variants (rs2268477, rs7144481, and rs17630128), the binding affinity of microRNAs (miRs) (hsa-miR-154-5p, hsa-miR-376a-2-5p, hsa-miR-3935, hsa-miR-4280, and hsa-miR-6858-3p) to the 3'-UTR is disrupted, affecting post-transcriptional gene regulation. TPO and TG are the two key proteins necessary for the biosynthesis of thyroid hormones in the presence of iodide and H₂O₂. Reduced stability of these proteins leads to aberrant biosynthesis of thyroid hormones. Compared to the wild-type TPO protein, the p.S398T variant was found to exhibit less stability and significant rearrangements of intra-atomic bonds affecting the stoichiometry and substrate binding (binding energies, ΔG of wild-type vs. mutant: -15 vs. -13.8 kcal/mol; and dissociation constant, K_d of wild-type vs. mutant: 7.2E^-12 vs. 7.0E^-11 M). The missense mutations p.G653D and p.R1999W on the TG protein showed altered ΔG(0.24 kcal/mol and 0.79 kcal/mol, respectively). In conclusion, an in silico analysis of TSHR genetic variants in the 3'-UTR showed that they alter the binding affinities of different miRs. The TPO protein structure and mutant protein complex (p.S398T) are less stable, with potentially deleterious effects. A structural and energy analysis showed that TG mutations (p.G653D and p.R1999W) reduce the stability of the TG protein and affect its structure-functional relationship.

• Endocrinology and Metabolism
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• v.33 no.4
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• pp.466-472
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• 2018

Background: Thyroid dysfunction is associated with negative neonatal and obstetric outcomes. Large differences in thyroid function reference intervals exist across different populations. These differences can be explained by population-specific factors, such as iodine status. Many countries in Latin America report iodine sufficiency, but relatively few countries have published up-to-date data on iodine levels and thyroid function in the overall population, and especially in pregnant women. We evaluated the iodine status of pregnant women in Chile and determined thyroid hormone reference ranges in this population. Methods: This was a prospective observational study of healthy Chilean women at their first prenatal visit before week 14. Thyroid-stimulating hormone (TSH), total thyroxine ($T_4$), free $T_4$, antithyroid peroxidase antibody (TPOAb), and iodine levels from spot urine samples were measured. Iodine status and the reference ranges for TSH were calculated. Results: A total of 1,022 pregnant women in the first trimester were selected. Urinary iodine levels were measured in 302 randomly-selected women. The median urinary iodine concentration was $173.45{\mu}g/L$ (interquartile range, 108.11 to 249.35).The reference ranges of TSH were calculated in 670 patients selected according to the National Academy of Clinical Biochemistry guidelines. The median TSH level was $1.88{\mu}IU/mL$ (2.5th percentile: 0.13 to 97.5th percentile: 5.37). Using the reference range in the 1,022 women, the prevalence of clinical hypothyroidism was 1.76%, and that of subclinical hypothyroidism was 3.92%. TPOAb positivity was more common in women with TSH levels above $3.5{\mu}IU/mL$. Conclusion: We found adequate iodine intake and a right-shifted distribution of serum TSH levels in pregnant women in Chile. The prevalence of hypothyroidism in our sample of pregnant women was higher than has been described in the literature.

• Annals of Pediatric Endocrinology and Metabolism
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• v.23 no.4
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• pp.235-239
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• 2018

Most cases of congenital hyperthyroidism are autoimmune forms caused by maternal thyroid stimulating antibodies. Nonautoimmune forms of congenital hyperthyroidism caused by activating mutations of the thyrotropin receptor (TSHR) gene are rare. A woman gave birth to a boy during an emergency cesarean section at 33 weeks of gestation due to fetal tachycardia. On the 24th day of life, thyroid function tests were performed due to persistent tachycardia, and hyperthyroidism was confirmed. Auto-antibodies to TSHR, thyroid peroxidase, and thyroglobulin were not found. The patient was treated with propylthiouracil and propranolol, but hyperthyroidism was not well controlled. At 3 months of age, the patient had craniosynostosis and hydrocephalus, and underwent a ventriculoperitoneal shunt operation. Direct sequencing of the TSHR gene showed a heterozygous mutation of c.1899C>A (p.Asp633Glu) in exon 10. No mutations were discovered in any of the parents in a familial genetic study. We have reported a case of sporadic nonautoimmune congenital hyperthyroidism, by a missense mutation of the TSHR gene, for the first time in South Korea.

• Clinical and Experimental Pediatrics
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• v.48 no.6
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• pp.624-633
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• 2005

Purpose : This study analyzed the expression of HLA-DR and DQ genotypes and anti-thyroid autoantibodies[anti-thyroid peroxidase(TPO) and anti-thyroglobulin(TG) antibodies] in Korean patients with type 1 diabetes(T1DM) to investigate the susceptible HLA alleles to T1DM in Korea and the prevalence of thyroid autoantibodies and their significance for the development of thyroid disorders. Methods : A total of 59 Korean patients with type 1 diabetes[26 males, median age 13.7 years(range 5.7-29.9 years), diabetes duration 7.6 years(-1.7-22.5 years)] were enrolled in this study, and 200 healthy Koreans without a family history of diabetes were selected as a normal control for the comparison of HLA genotypes. Seventeen patients with anti-TPO or anti-TG were followed [median duration 3.96 years(1 day-10.7 years)] with measurement of anti-TPO, anti-TG, $T_3$, $T_4$ or free $T_4$, TSH levels and physical examinations. HLA-DR and DQ genotyping were done by PCR-SSO, PCR-SSCP, PCR-RFLP and PCR-SSP methods. Results : HLA analysis showed higher frequencies of HLA-DRB1*0301, *090102 and DQB1*0201, *030302 alleles, DRB1*0301/*090102, *090102/*090102 and DQB1 *0201/*030302, *030302/*030302, *0201/ *0302 genotypes in T1DM patients compared to controls(Pc<0.05). Fifteen(25.4 percent) had anti-TPO antibody, 12(20.3 percent) had anti-TG, 17(28.8 percent) had either autoantibody and 10(16.9 percent) had both autoantibodies. No clinical or subclinical hypothyroidism developed during follow-up after the first detection of anti-thyroid autoantibody. There was no significant correlation between thyroid autoimmunity and gender, onset age of T1DM, and diabetes duration, respectively(P>0.05). Conclusion : We thought this unique HLA-DR, DQ allele distribution might be an important factor for the low incidence of T1DM in Korea. And a high prevalence of thyroid autoantibodies in these populations suggests examinations of thyroid antibodies should be performed regularly. Optimal age for the initial screening and the frequency of re-screening for associated thyroid autoimmune diseases in T1DM remains to be determined through prospective follow-up.

• Clinical and Experimental Reproductive Medicine
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• v.24 no.1
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• pp.143-151
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• 1997

The present study was designed to investigate if antithyroid antibodies (ATA) could affect the pregnancy outcome in euthyroid women undergoing in vitro fertilization and embryo transfer (IVF-ET). From October 1995 to September 1996, 28 euthyroid women with ATA who underwent IVF-ET were studied. Fifty-one euthyroid women without ATA who underwent IVF-ET served as control. Thyroid peroxidase antibody (TPOA) and thyroglobulin antibody (TGA) were assayed using radio ligand assay kits as ATA. All patients included in study and control groups had only tubal factor in infertility. Long protocol of gonadotropin-releasing hormone agonist (GnRH-a) was used for controlled ovarian hyperstimulation (COH) in all patients. There were no significant differences between study and control groups in patient characteristics such as age, infertility duration and hormonal profile. There were also no significant differences between two groups with respect to the clinical response to COH and IVF results such as number of retrieved oocytes, fertilization rate, number of embryos frozen and number of embryos transfered. There were no correlations between ATA (TPOA and TGA) titers and fertilization rate. The clinical pregnancy rate per cycle seemed to be lower in the study group than in the control group (26.3% vs 39.3%), but the difference was not statistically significant. The biochemical pregnancy rate per cycle and miscarriage rate were significantly higher in the study group at 18.4% (7/38) and 40.0% (4/10) compared with 5.6% (5/89) and 11.4% (4/35) in the control group. In the study group, both TPOA and TGA titers were significantly higher in the biochemical pregnancy group than in the clinical pregnancy group or non-pregnancy group. In 10 women with ATA who achieved pregnancy following IVF-ET, both TPOA and TGA titers were significantly higher in the miscarriage group than in the ongoing or delivery group. In conclusion, euthyroid women with ATA appear to represent a less favorable subset within other tubal factor patients when treated with IVF-ET.