Effects of pre- and postnatal exposure to chlorinated dioxins and furans on human neonatal thyroid hormone concentrations.

Animal studies have shown that dioxins influence plasma thyroid hormone concentrations. To investigate the effect of chlorinated dioxins and furans on thyroid hormone concentrations in humans, we studied 38 healthy breast-fed infants. The study population was divided into two groups according to the dioxin concentrations in milk fat of their mothers. Blood samples were taken at birth and at the ages of 1 and 11 weeks. At birth a tendency to higher total thyroxine (tT4) concentrations was found in the high exposure group. At the ages of 1 and 11 weeks the increase of mean tT4 concentrations and tT4/thyroxine-binding globulin ratios in the high exposure group reached significance as compared to the low exposure group. At birth and 1 week after birth, mean thyrotropin (TSH) concentrations were similar in both groups, but at the age of 11 weeks the mean TSH concentrations were significantly higher in the high exposure group. We postulate that the observed plasma tT4 elevation in infants exposed to dioxins before and after birth is the result of an effect on the thyroid hormone regulatory system

Neonatal screening for congenital hypothyroidism in the Netherlands: Cognitive and motor outcome at 10 years of age

Contains fulltext : 35300.pdf (publisher's version ) (Open Access)CONTEXT: Patients with thyroidal congenital hypothyroidism (CH-T) born in The Netherlands in 1981-1982 showed persistent intellectual and motor deficits during childhood and adulthood, despite initiation of T(4) supplementation at a median age of 28 d after birth. OBJECTIVE: The present study examined whether advancement of treatment initiation to 20 d had resulted in improved cognitive and motor outcome. DESIGN/SETTING/PATIENTS: In 82 Dutch CH-T patients, born in 1992 to 1993 and treated at a median age of 20 d (mean, 22 d; range, 2-73 d), cognitive and motor outcome was assessed (mean age, 10.5 yr; range, 9.6-11.4 yr). Severity of CH-T was classified according to pretreatment free T(4) concentration. MAIN OUTCOME MEASURE: Cognitive and motor outcome of the 1992-1993 cohort in comparison to the 1981 to 1982 cohort was the main outcome measure. RESULTS: Patients with severe CH-T had lower full-scale (93.7), verbal (94.9), and performance (93.9) IQ scores than the normative population (P < 0.05), whereas IQ scores of patients with moderate and mild CH-T were comparable to those of the normative population. In all three severity subgroups, significant motor problems were observed, most pronounced in the severe CH-T group. No correlations were found between starting day of treatment and IQ or motor outcome. CONCLUSIONS: Essentially, findings from the 1992-1993 cohort were similar to those of the 1981-1982 cohort. Apparently, advancing initiation of T(4) supplementation from 28 to 20 d after birth did not result in improved cognitive or motor outcome in CH-T patients

Structure and characterization of a 50 bp repeat in intron 10 of the human thyroid peroxidase gene

We have previously identified an EcoRI polymorphism detected by a human thyroid peroxidase (hTPO) cDNA probe, with alleles varying in size from 3.0 to 4.1 kb. For further characterization of this polymorphism, we have cloned the genomic region containing this polymorphism. Sequence analysis of a 3.2 kb EcoRI fragment containing the polymorphism revealed nine copies of a 50 bp direct repeat located 1.9 kb downstream of exon 10. In 50 unrelated Caucasian individuals, the number of repeats was determined and varied from 9 to 31, with an average of 21. Since exon 10 has been shown to be alternatively spliced in hTPO mRNA, we have also tested whether the number of 50 bp repeats affects alternative splicing of exon 10. We find no correlation between the number of repeats in intron 10 and the ratio of alternatively spliced hTPO-1 and hTPO-2 mRNA in six human thyroid gland

Inborn errors of thyroid hormone biosynthesis

Permanent congenital hypothyroidism in the Netherlands (incidence 1:3000) is caused for 70-80% by a- or dysgenesis of the thyroid gland, for about 15% by dyshormonogenesis and for 10-15% by hypothalamic-pituitary disturbances. The heredity of congenital hypothyroidism caused by dyshormonogenesis is mendelian in character and follows, with a few exceptions, an autosomal recessive pattern. The diagnosis of these inborn errors is based on a combination of imaging studies, plasma hormone and thyroglobulin concentrations, and the concentration of iodide and iodinated peptides in the urine. The contribution of molecular biology is becoming an important factor in the classification of hereditary congenital hypothyroidis

Serum thyroglobulin levels in preterm infants with and without respiratory distress syndrome. II. A longitudinal study during the first 3 weeks of life

Serum thyroglobulin (Tg) and thyroid-stimulating hormone (TSH) levels were measured in 182 preterm and term infants. Samples were taken from cord blood, and at 1, 3, 7, 14, and 21 days after birth. The infants were divided into groups according to their perinatal characteristics: infants who were appropriate for gestational age, infants who were small for gestational age, and preterm infants who developed respiratory distress syndrome. These groups were subdivided according to gestation age. Tg serum levels showed a significant increase in the 1st day in all groups, and decreased significantly after about 1 wk. The highest Tg levels were found in the 1st wk of life in respiratory distress syndrome infants, and in infants with the lowest gestation ages. TSH levels increased at day 1 but only in appropriate and small for gestational age infants of more than 30 wk of gestation. TSH levels at day 1 in the groups with gestation ages of less than 30 wk and in respiratory distress syndrome infants of more than 30 wk were low, reflecting a low TSH surge. We conclude that the neonatal increase of Tg is not merely caused by the TSH surge. We suggest that the Tg increase is due to an impaired degradation of Tg, and/or to hemoconcentration, which are more pronounced in respiratory distress syndrome infants compared with appropriate for gestational age infant