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In the Italian population sexual dimorphism affects pre-natal thyroid migration but not biochemical severity of gland ectopia and pre-natal bone maturation

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Abstract

The aim of the present study was to retrospectively re-evaluate a population of selected infants with congenital hypothyroidism (CH), in order to investigate whether sexual dimorphism affects: a) CH etiology; b) its biochemical severity at the time of screening and recall; c) patients’ biochemical response to replacement treatment during the 1st yr of life; d) their bone maturation (BM) at birth; e) their psychomotor status at 1 yr. This retrospective study covers 192 infants (116 females) with persistent CH who were selected from a larger population of CH patients identified during a 10-yr period (1990–1999) by the screening programs of 5 northern, central, and southern regions of Italy. Thirty boys (39.5%) and 66 girls (56.9%) were found to have ectopia, whereas the remaining 46 boys and 50 girls exhibited the other causes of CH. When compared with the prevalence of the remaining causes that of ectopia was significantly higher in girls than in boys (66/116 vs 30/76; χ2=5.57, p<0.025), and sex ratio in ectopia was significantly different also compared with the orthotopic gland group only (66/84 vs 30/51; χ2=6.02, p<0.025). No differences between males and females were detected in the groups with either athyreosis or orthotopic gland. In no groups were there differences between sexes for gestational age, birth auxological data, percentage of newborns with bone retardation or developmental quotient at 1 yr. Thyroid tests at birth, age at TSH normalization and average thyroid tests under L-T4 treatment during the 1st yr did not differ between sexes in any of the groups. Conclusions: a) in the Italian population sexual dimorphism affects pre-natal thyroid migration but neither biochemical severity of ectopia, nor pre-natal bone maturation and psychomotor development; b) girls with CH do not require higher doses of initial therapy in order to achieve TSH normalization; c) future developmental and molecular studies on ectopia etiology in CH need to take into account the effect of sexual dimorphism.

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References

  1. Reddy S, Yip S, Karanam M, Poole CA, Ross JM. An immunohistochemical study of macrophage influx and the co-localization of inducible nitric oxide synthase in the pancreas of non-obese diabetic (NOD) mice during disease acceleration with cyclophosphamide. Histochem J 1999, 31: 303–14.

    Article  PubMed  CAS  Google Scholar 

  2. Ventura-Oliveira D, Vilella CA, Zanin ME, Castro GM, Moreira Filho DC, Zollner RL. Kinetics of TNF-alpha and IFN-gamma mRNA expression in islets and spleen of NOD mice. Braz J Med Biol Res 2002, 35: 1347–55.

    Article  PubMed  CAS  Google Scholar 

  3. Rabinovitch A, Suarez-Pinzon WL, Sorensen O, Bleackley RC. Inducible nitric oxide synthase (iNOS) in pancreatic islets of nonobese diabetic mice: identification of iNOS-expressing cells and relationships to cytokines expressed in the islets. Endocrinology 1996, 137: 2093–9.

    PubMed  CAS  Google Scholar 

  4. Darville Ml, Eizirik DL. Regulation by cytokines of the inducible nitric oxide synthase promoter in insulin-producing cells. Diabetologia 1998, 41: 1101–8.

    Article  PubMed  CAS  Google Scholar 

  5. Eizirik DL, Sandier S, Welsh N, et al. Cytokines suppress human islet function irrespective of their effects on nitric oxide generation. J Clin Invest 1994, 93: 1968–74.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  6. Corbett JA, Lancaster JR Jr, Sweetland MA, McDaniel ML. lnterleukin-1 beta-induced formation of EPR-detectable iron-nitrosyl complexes in islets of Langerhans. Role of nitric oxide in interleukin-1 beta-induced inhibition of insulin secretion. J Biol Chem 1991, 266: 21351–4.

    PubMed  CAS  Google Scholar 

  7. Karlsen AE, Pavlovic D, Nielsen K, et al. Interferon-gamma induces interleukin-1 converting enzyme expression in pancreatic islets by an interferon regulatory factor-1-dependent mechanism. J Clin Endocrinol Metab 2000, 85: 830–6.

    PubMed  CAS  Google Scholar 

  8. Cetkovic-Cvrlje M, Eizirik DL. TNF-alpha and IFN-gamma potentiate the deleterious effects of IL-1 beta on mouse pancreatic islets mainly via generation of nitric oxide. Cytokine 1994, 6: 399–406.

    Article  PubMed  CAS  Google Scholar 

  9. Zumsteg U, Frigerio S, Holländer GA. Nitric oxide production and Fas surface expression mediate two independent pathways of cytokine-induced murine beta-cell damage. Diabetes 2000, 49: 39–47.

    Article  PubMed  CAS  Google Scholar 

  10. Yamada K, Otabe S, Inada C, Takane N, Nonaka K. Nitric oxide and nitric oxide synthase mRNA induction in mouse islet cells by interferon-gamma plus tumor necrosis factor-alpha. Biochem Biophys Res Commun 1993, 197: 22–7.

    Article  PubMed  CAS  Google Scholar 

  11. Liu D, Pavlovic D, Chen MC, Flodström M, Sandler S, Eizirik DL. Cytokines induce apoptosis in beta-cells isolated from mice lacking the inducible isoform of nitric oxide synthase (iNOS-/-). Diabetes 2000, 49: 1116–22.

    Article  PubMed  CAS  Google Scholar 

  12. Andersson AK, Flodström M, Sandler S. Cytokine-induced inhibition of insulin release from mouse pancreatic betacells deficient in inducible nitric oxide synthase. Biochem Biophys Res Commun 2001, 281: 396–403.

    Article  PubMed  CAS  Google Scholar 

  13. Flodström M, Tyrberg B, Eizirik DL, Sandler S. Reduced sensitivity of inducible nitric oxide synthase-deficient mice to multiple low-dose streptozotocin-induced diabetes. Diabetes 1999, 48: 706–13.

    Article  PubMed  Google Scholar 

  14. Takamura T, Kato I, Kimura N, et al. Transgenic mice over-expressing type 2 nitric-oxide synthase in pancreatic beta cells develop insulin-dependent diabetes without insulitis. J Biol Chem 1998, 273: 2493–6.

    Article  PubMed  CAS  Google Scholar 

  15. Drucker DJ. The biology of incretin hormones. Cell Metab 2006, 3: 153–65.

    Article  PubMed  CAS  Google Scholar 

  16. Li L, El-Kholy W, Rhodes CJ, Brubaker PL. Glucagon-like peptide-1 protects beta cells from cytokine-induced apoptosis and necrosis: role of protein kinase B. Diabetologia 2005, 48: 1339–49.

    Article  PubMed  CAS  Google Scholar 

  17. Hui H, Nourparvar A, Zhao X, Perfetti R. Glucagon-like peptide-1 inhibits apoptosis of insulin-secreting cells via a cyclic 5′-adenosine monophosphate-dependent protein kinase A- and a phosphatidylinositol 3-kinase-dependent pathway. Endocrinology 2003, 144: 1444–55.

    Article  PubMed  CAS  Google Scholar 

  18. Iwai T, Ito S, Tanimitsu K, Udagawa S, Oka J. Glucagon-like peptide-1 inhibits LPS-induced IL-1 beta production in cultured rat astrocytes. Neurosci Res 2006, 55: 352–60.

    Article  PubMed  CAS  Google Scholar 

  19. Li Y, Hansotia T, Yusta B, Ris F, Halban PA, Drucker DJ. Glucagon-like peptide-1 receptor signaling modulates beta cell apoptosis. J Biol Chem 2003, 278: 471–8.

    Article  PubMed  CAS  Google Scholar 

  20. Green LC, Wagner DA, Glogowski J, Skipper PL, Wishnok JS, Tannenbaum SR. Analysis of nitrate, nitrite, and [15N]nitrate in biological fluids. Anal Biochem 1982, 126: 131–8.

    Article  PubMed  CAS  Google Scholar 

  21. Jun HS, Yoon CS, Zbytnuik L, van Rooijen N, Yoon JW. The role of macrophages in T cell-mediated autoimmune diabetes in nonobese diabetic mice. J Exp Med 1999, 189: 347–58.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  22. Yada T, Itoh K, Nakata M. Glucagon-like peptide-1-(7-36)amide and a rise in cyclic adenosine 3′,5′-monophosphate increase cytosolic free Ca2+ in rat pancreatic betacells by enhancing Ca2+ channel activity. Endocrinology 1993, 133: 1685–92.

    PubMed  CAS  Google Scholar 

  23. Drucker DJ. Glucagon-like peptides: regulators of cell proliferation, differentiation, and apoptosis. Mol Endocrinol 2003, 17: 161–71.

    Article  PubMed  CAS  Google Scholar 

  24. Kim WH, Lee JW, Gao B, Jung MH. Synergistic activation of JNK/SAPK induced by TNF-alpha and IFN-gamma: apoptosis of pancreatic beta-cells via the p53 and ROS pathway. Cell Signal 2005, 17: 1516–32.

    Article  PubMed  CAS  Google Scholar 

  25. Suk K, Kim S, Kim YH, et al. IFN-gamma/TNF-alpha synergism as the final effector in autoimmune diabetes: a key role for STAT1/IFN regulatory factor-1 pathway in pancreatic beta cell death. J Immunol 2001, 166: 4481–9.

    Article  PubMed  CAS  Google Scholar 

  26. Chang I, Cho N, Kim S, et al. Role of calcium in pancreatic islet cell death by IFN-gamma/TNF-alpha. J Immunol 2004, 172: 7008–14.

    Article  PubMed  CAS  Google Scholar 

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Correspondence to F. De Luca MD.

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Wasniewska, M., Arrigo, T., Crisafulli, G. et al. In the Italian population sexual dimorphism affects pre-natal thyroid migration but not biochemical severity of gland ectopia and pre-natal bone maturation. J Endocrinol Invest 31, 341–345 (2008). https://doi.org/10.1007/BF03346368

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