Maternal compound W serial measurements for the management of fetal hypothyroidsm.
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OBJECTIVE: The diagnosis of fetal hypothyroidism is based at present on measurements of TSH and free thyroxine (FT4) in fetal blood samples obtained by cordocentesis. The measurement of maternal serum and urinary concentrations of compound W, immunologically similar to but chromatographically distinct from diiodothyronine sulfate (T2S), has been advocated as a new possible marker for fetal hypothyroidism. DESIGN: In this paper, we measured serum compound W levels in 84 pregnant women, 20 with and 64 without thyroid disorders before and during specific treatment. Compound W was also assessed in fetal blood obtained by cordocentesis from 49 normal fetuses and 4 fetuses with suspected hypothyroidism due to transplacental passage of propylthiouracil (PTU). Compound W levels were measured by T2S RIA in maternal and fetal serum. To assess the possible usefulness of 3, 5,3'-triiodothyroacetic acid (TRIAC) for therapy of fetal hypothyroidism we evaluated the transplacental passage of TRIAC by administering the drug to four pregnant women before therapeutic abortion. RESULTS: In normal pregnancies, both maternal and fetal compound W levels increased progressively during gestation with a significant direct correlation (P<0.001, in both mothers and fetuses). Moreover, a significant positive correlation was observed between fetal compound W and fetal FT4 values (P<0.005), whereas no correlation was observed between maternal serum compound W and maternal FT4 in either euthyroid or hyperthyroid women, suggesting the fetal origin of compound W. The hypothyroid fetuses of PTU-treated mothers showed low compound W levels, and maternal compound W values were in the low normal range and did not show the typical increase during progression of gestation. A significant increase of maternal compound W was observed when the PTU dose was reduced. TRIAC was documented to cross the placental barrier and the treatment of a hyperthyroid pregnant woman on PTU caused the high fetal TSH levels and goiter to normalize. CONCLUSIONS: Serial measurements of 3,3'-T2S crossreactive materials (compound W and 3, 3'-diiodothyroacetic acid sulfate) in maternal blood and the administration of TRIAC to the mother may represent a useful and safe alternative to invasive techniques for the diagnosis and therapy of fetal hypothyroidism. (+info)
Hormonal changes during the first year of oestrogen treatment in constitutionally tall girls.
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OBJECTIVE: Oestrogens are used to inhibit growth in girls with constitutionally tall stature. We studied the changes in different hormones that accompany such therapy. SUBJECTS AND METHODS: In this longitudinal study we examined the levels of total insulin-like growth factor-I (IGF-I), free thyroxine (FT(4)), thyrotrophin (TSH), testosterone, dehydroepiandrosterone sulphate (DHEA-S), cortisol and prolactin in two groups of girls receiving ethinyloestradiol at a dose of either 0.1mg daily (group A, n=22) or 0.2mg daily (group B, n=36). Hormonal measurements were performed at start of therapy and after 3, 6 and 12 months. RESULTS: In both groups the levels of IGF-I, testosterone and DHEA-S were reduced while the concentrations of cortisol and prolactin were increased. The pituitary-thyroid axis was not significantly affected by this therapy. The girls receiving 0.2mg ethinyloestradiol daily had lower IGF-I levels after 12 months of therapy and had higher serum prolactin concentrations than the girls treated with 0.1mg daily. The reduction in predicted height and the advancement in bone age were similar in both groups. CONCLUSIONS: Therapy with pharmacological doses of ethinyloestradiol changes the levels of several hormones including IGF-I, testosterone, DHEA-S, prolactin and cortisol but the role of the respective changes in the inhibition of growth is not clear. The suppression of DHEA-S levels by 40% suggests that the ovaries contribute significantly to the production of this hormone in pubertal girls. (+info)
Cyclin D3 accumulation and activity integrate and rank the comitogenic pathways of thyrotropin and insulin in thyrocytes in primary culture.
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The proliferation of most normal cells depends on the synergistic interaction of several growth factors and hormones, but the cell cycle basis for this combined requirement remains largely uncharacterized. We have addressed the question of the requirement for insulin/IGF-1 also observed in many cell culture systems in the physiologically relevant system of primary cultures of dog thyroid epithelial cells stimulated by TSH, which exerts its mitogenic activity only via cAMP. The induction of cyclin A and cdc2, the phosphorylation of cdk2, the nuclear translocation of cdk4 and the assembly of cyclin D3-cdk4 complexes required the synergy of TSH and insulin. Cyclin D3 (the most abundant cyclin D) was necessary for the proliferation stimulated by TSH in the presence of insulin as shown by microinjection of a neutralizing antibody. Cyclin D3 accumulation and activity were differentially regulated by insulin and TSH, which points out this cyclin as an integrator that ranks these comitogenic pathways as supportive and activatory, respectively. Paradoxically TSH alone strongly repressed cyclin D3 accumulation. This inhibition was overridden by insulin, which markedly stimulated cyclin D3 mRNA and protein accumulation, but failed to assemble cyclin D3-cdk4 complexes in the absence of TSH. TSH unmasked the DCS-22 epitope of cyclin D3 and assembled cyclin D3-cdk4 in the presence of insulin. These data demonstrate that cyclin D synthesis and cyclin D-cdk assembly can be dissociated and complementarily regulated by different agents and signalling pathways. (+info)
Maternal thyroid function in multifetal pregnancies before and after fetal reduction.
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The aim of the study was to investigate maternal thyroid function in pregnancy by monitoring the circulating concentrations of thyroid stimulating hormone (TSH), free thyroxine (fT(4)) and human chorionic gonadotrophin (hCG) in multifetal pregnancies before and after embryo reduction. We studied two groups of women: group 1 comprised singleton (n=12) and twin (n=12) pregnancies achieved after superovulation and in vitro fertilisation and embryo transfer (IVF-ET), and group 2 were multifetal pregnancies (n=39) undergoing selective fetal reduction to twin pregnancies. Blood samples were obtained initially at 10-12 weeks gestation (before fetal reduction) and then 4 and 8 weeks afterwards. Before fetal reduction, the circulating concentrations of fT(4) in multifetal pregnancies were significantly greater than those in singleton or twin pregnancies (singleton, mean 16.49 pmol/l (interquartile range 14.09-18.13 pmol/l); twins, 15.84 (15.36-16.95 pmol/l); multifetal, 21.08 (16. 64-26.29 pmol/l); P<0.005 for singleton and twins), and in a multiple regression analysis, fT(4) was significantly related to the number of fetuses (F=23.739, P=0.0001), but not to hCG. After fetal reduction to twins, the circulating concentrations of fT(4) in multifetal pregnancies decreased progressively towards those in control twin pregnancies, but remained significantly greater at both 4 (P=0.003) and 8 weeks (P=0.050). This pattern of change in the concentrations of fT(4) is similar to, but lags behind, that of hCG, which attains twin levels 4 weeks after fetal reduction. This may represent a delayed thyroid response to the decreasing concentrations of hCG, but the alternative is that the maternal thyroid function is controlled by a fetal factor in addition to hCG. (+info)
Endemic goiter with iodine sufficiency: a possible role for the consumption of pearl millet in the etiology of endemic goiter.
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BACKGROUND: Deficiencies of iodine, iron, and vitamin A are the 3 most common micronutrient deficiencies in developing countries, although control programs, when properly implemented, can be effective. OBJECTIVE: We investigated these deficiencies and their possible interaction in preschool children in the southern Blue Nile area of Sudan. DESIGN: Goiter, signs of vitamin A deficiency, and biochemical markers of thyroid, vitamin A, and iron status were assessed in 984 children aged 1-6 y. RESULTS: The goiter rate was 22. 3%. The median urinary iodine concentration was 0.79 micromol/L and 19.3% of the children had a concentration >1.57 micromol/L. Although serum thyroxine and triiodothyronine concentrations were within reference ranges, the median thyrotropin concentration was 3.78 mIU/L and 44% of the children had thyrotropin concentrations above normal. The mean urinary thiocyanate concentration was high (259 +/- 121 micromol/L). The prevalences of Bitot spots and night blindness were 2.94% and 2.64%, respectively, and 32% of the subjects had serum retinol binding protein concentrations <15 mg/L. A significant positive correlation was observed between thyrotropin and retinol binding protein. Whereas 88% of the children had hemoglobin concentrations <1.86 mmol/L, only 13.5% had serum ferritin concentrations below the cutoff of 12 microg/L and 95% had serum transferrin concentrations above the cutoff of 2.50 g/L. CONCLUSIONS: Our results indicate that goiter is endemic in this region of Sudan despite iodine sufficiency and that both anemia and vitamin A deficiency are health problems in the area. Moreover, consumption of millet, vitamin A deficiency, and protein-energy malnutrition are possible etiologic factors in this endemic area. (+info)
Persistence of goiter despite oral iodine supplementation in goitrous children with iron deficiency anemia in Cote d'Ivoire.
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BACKGROUND: In developing countries, many children are at high risk of goiter and iron deficiency anemia. Because iron deficiency can have adverse effects on thyroid metabolism, iron deficiency may influence the response to supplemental iodine in areas of endemic goiter. OBJECTIVE: The aim of this study was to determine whether goitrous children with iron deficiency anemia would respond to oral iodine supplementation. DESIGN: A trial of oral iodine supplementation was carried out in an area of endemic goiter in western Cote d'Ivoire in goitrous children (n = 109) aged 6-12 y. Group 1 (n = 53) consisted of goitrous children who were not anemic. Group 2 (n = 56) consisted of goitrous children who had iron deficiency anemia. At baseline, thyroid gland volume and urinary iodine, thyrotropin, and thyroxine were measured by using ultrasound. Each child received 200 mg I orally and was observed for 30 wk, during which urinary iodine, thyrotropin, thyroxine, hemoglobin, and thyroid gland volume were measured. RESULTS: The prevalence of goiter at 30 wk was 12% in group 1 and 64% in group 2. The mean percentage change from baseline in thyroid volume 30 wk after administration of oral iodine was -45.1% in group 1 and -21.8% in group 2 (P < 0.001). Among the anemic children, there was a strong correlation between the percentage decrease in thyroid volume and hemoglobin concentration (r(2) = 0.65). CONCLUSION: The therapeutic response to oral iodine was impaired in goitrous children with iron deficiency anemia, suggesting that the presence of iron deficiency anemia in children limits the effectiveness of iodine intervention programs. (+info)
The role of selenium in iodine metabolism in children with goiter.
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Possible interactions between selenium and iodine metabolism were investigated in 7- to 16-year-old children with goiter (n = 136) living in southeastern Poland in iodine-deficient areas influenced by a sulfur industry. The Se-iodine interactions in these children were compared to the interactions in children from outside of that region (n = 38). Blood selenium (BSe) concentration and plasma glutathione peroxidase activity were much lower in the study group (64.1 +/- 15.7 microg/L; 111.0 +/- 27.6 U/L) than in the control group (85.3 +/- 19.6 microg/L; 182.4 +/- 35.6 U/L). Almost all of the data [plasma thyroid-stimulating hormone (TSH) concentration, plasma free thyroxine (fT(4)) concentration] fell within the reference limits. There was no statistically significant difference between the control and the study groups with respect to fT(4) and TSH. However, statistically significant differences of fT(4) and TSH in the study group were revealed between females belonging to the lower (n = 21; fT(4), 16.1 +/- 3.3 pmol/L; TSH, 1.83 +/- 1.05 mU/L) and upper Se quartiles (n = 24; fT(4), 14.5 +/- 2.2 pmol/L; TSH, 1. 26 +/- 0.90 mU/L), p < 0.05. Neither group differed in iodine in urine concentration, age, and body mass index. The difference in fT(4) concentrations can be attributed to an Se deficiency. The relationship exists only for females, which suggests a sex-linked hormonal response to concomitant Se and iodine deficiencies. (+info)
Hyperproliferative hepatocellular alterations after intraportal transplantation of thyroid follicles.
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The thyroid hormone 3,5,3'-triiodo-L-thyronine (T3) is a strong direct hepatocyte mitogen in vivo. The effects of T3 resemble those of peroxisome proliferators, which are known to induce hepatocellular tumors in rats. With the aim of studying long-term local effects of thyroid hormones on liver parenchyma, small pieces of thyroid tissue were transplanted via the portal veins into the livers of thyroidectomized male Lewis rats. At 1 week, 3 weeks, 3 months, and 18 months after transplantation, the transplants were found to proliferate, to synthesize thyroglobulin, and to release thyroxine and T3. At 3 and 18 months after transplantation, the hepatocytes of the liver acini downstream of the transplanted follicles showed an increase in cytoplasmic basophilia, a loss of glycogen, an enlargement and hyperchromasia of their nuclei, and a strong increase in cell turnover compared with unaltered liver acini. The altered hepatocytes exhibited an increase in the activities of glucose-6-phosphate dehydrogenase, glucose-6-phosphatase, malic enzyme, mitochondrial glycerol-3-phosphate dehydrogenase, cytochrome-c-oxidase, and acid phosphatase; the activities of glycogen synthase and glycogen phosphorylase were strongly decreased. The hepatocytic alterations downstream of the transplanted follicles could be explained by effects of T3. On the other hand, they resembled alterations characteristic of amphophilic preneoplastic liver foci observed in different models of hepatocarcinogenesis. (+info)