Advertisement

European Journal of Epidemiology

, Volume 26, Issue 5, pp 405–411 | Cite as

Space–time clustering of elevated thyroid stimulating hormone levels

  • Mark S. Pearce
  • Richard J. Q. McNally
  • Julie Day
  • S. Murthy Korada
  • Steve Turner
  • Tim D. Cheetham
ENDOCRINE EPIDEMIOLOGY

Abstract

Previous studies of congenital hypothyroidism (CHT) have reported an increasing incidence which may suggest that environmental factors play an aetiological role. If so, then cases may exhibit space–time clustering, where cases occur at similar times and close proximities to other cases. In this study we investigated whether space–time clustering of elevated thyroid stimulating hormone (TSH) in newborns exists. All infants born in the Northern Region of England are screened by measuring levels of circulating TSH using a blood spot assay. Data on 207 cases of elevated TSH values, as a proxy for CHT, in newborns born from 1994 to 2006 inclusive were available and analysed using rigorous space–time clustering statistical methods. Analysis showed statistically significant evidence of space–time clustering. The strength of clustering was most marked for cases born within 0.1–0.7 year (1–8 months) of one another. This is the first study to find significant space–time clustering of cases of elevated TSH levels in newborns, a surrogate for space–time clustering of CHT. Whilst the reasons for the clustering are unclear, it would appear from this analysis that transient environmental exposures are likely to be involved, although environmental determinants of genetic mutations and epigenetic factors cannot be ruled out. Further research is required to a) validate these results in other populations and b) to assess in more detail the potential environmental determinants of increased CHT risk.

Keywords

Congenital hypothyroidism TSH Clustering Thyroid Pediatric endocrinology 

Notes

Acknowledgments

We would like to thank David Allison for his help in collecting and compiling these data.

Conflict of interest

There is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported. This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.

Supplementary material

10654_2011_9571_MOESM1_ESM.doc (94 kb)
Supplementary material 1 (DOC 93 kb)

References

  1. 1.
    Van Vliet G. Development of the thyroid gland: lessons from congenitally hypothyroid mice and men. Clin Genet. 2003;63:445–455.Google Scholar
  2. 2.
    Pearce MS, Korada M, Day J, Turner S, Allison D, Kibirige M, et al. Increasing incidence, but lack of seasonality, of elevated TSH levels, on newborn screening, in the North of England. J Thyroid Res [in press].Google Scholar
  3. 3.
    Harris KB, Pass KA. Increase in congenital hypothyroidism in New York State and in the United States. Mol Genet Metabolism 2007;91:268–277.Google Scholar
  4. 4.
    Rendón-Macías ME, Morales-García I, Huerta-Hernández E, Silva-Batalla A, Villasís-Keever MA. Birth prevalence of congenital hypothyroidism in Mexico. Paediatr Perinatal Epidemiol. 2008;22:478–485.Google Scholar
  5. 5.
    Hall SK, Hutchesson ACJ, Kirk JM. Congenital hypothyroidism, seasonality and consanguinity in the West Midlands, England. Acta Paediatrica. 1999;88:212–215.Google Scholar
  6. 6.
    Deladoëy J, Bélanger N, Van Vliet G. Random variability in congenital hypothyroidism from thyroid dysgenesis over 16 years in Quebec. J Clin Endocrinol Metabol. 2007;92:3158–3161.Google Scholar
  7. 7.
    Hinton CF, Harris KB, Borgfeld L, Drummond-Borg M, Eaton R, Lorey F, Therrell BL, Wallace J, Pass KA. Trends in incidence rates of congenital hypothyroidism related to select demographic factors: data from the United States, California, Massachusetts, New York, and Texas. Pediatrics. 2010;125(2):S37–S47.Google Scholar
  8. 8.
    Korada M, Pearce M, Avis E, Turner S, Cheetham T. TSH levels in relation to gestation, birth weight and sex. Horm Res. 2009;72:120–123.Google Scholar
  9. 9.
    Jones JH, Mackenzie J, Croft GA, Beaton S, Young D, Donaldson MD. Improvement in screening performance and diagnosis of congenital hypothyroidism in Scotland 1979–2003. Archives Dis Child. 2006;91:680–685.Google Scholar
  10. 10.
    Ahmed SF, Barnes ND, Hughes IA. Initial evaluation of congenital hypothyroidism: a survey of general paediatricians in East Anglia. Archives Dis Child. 1997;77:339–341.Google Scholar
  11. 11.
    Perry RJ, Maroo S, Maclennan AC, Jones JH, Donaldson MD. Combined ultrasound and isotope scanning is more informative in the diagnosis of congenital hypothyroidism than single scanning. Archives Dis Child. 2006;91:972–976.Google Scholar
  12. 12.
    Oppenheimer JH, Braverman LE, Toft A, Jackson IM, Ladenson PW. 1995 A therapeutic controversy. Thyroid hormone treatment: when and what? J Clin Endocrinol Metabol. 1995;80:2873–2883.Google Scholar
  13. 13.
    Diggle PJ, Chetwynd AG, Haggkvist R, Morris SE. Second-order analysis of space-time clustering. Stat Methods Med Res. 1995;4:124–136.Google Scholar
  14. 14.
    Knox EG. The detection of space-time interactions. Appl Stat. 1964;13:25–29.Google Scholar
  15. 15.
    McNally RJ, Alexander FE, Bithell JF. Space-time clustering of childhood cancer in Great Britain: a national study, 1969–1993. Int J Cancer. 2006;118:2840–2846.Google Scholar
  16. 16.
    McNally RJ, Feltbower RG, Parker L, Bodansky HJ, Campbell F, McKinney PA. Space-time clustering analysis of type 1 diabetes among 0- to 29- year-olds in Yorkshire, UK. Diabetologia. 2006;49:900–904.Google Scholar
  17. 17.
    McNally RJ, Rankin J, Shirley MD, Rushton SP, Pless-Mulloli T. Space- time analysis of Down syndrome: results consistent with transient pre-disposing contagious agent. Int J Epidemiol. 2008;37:1169–1179.Google Scholar
  18. 18.
    Jacquez GM. A k nearest neighbour test for space-time interaction. Stat Med. 1996;15:1935–1949.Google Scholar
  19. 19.
    Vassart G, Dumont JE. Thyroid dysgenesis: multigenic or epigenetic… or both? Endocrinol. 2005;146:5035–5037.Google Scholar
  20. 20.
    Calaciura F, Motta RM, Miscio G, Fichera G, Leonardi D, Carta A, Trischitta V, Tassi V, Sava L, Vigneri R. Subclinical hypothyroidism in early childhood: a frequent outcome of transient neonatal hyperthyrotropinemia. J Clin Endocrinol Metabol. 2002;87:3209–3214.Google Scholar
  21. 21.
    Daliva AL, Linder B, Di Martino-Nardi J, Saenger P. Three-year follow-up of borderline congenital hypothyroidism. J Pediatrics. 2000;136:53–56.Google Scholar
  22. 22.
    Corbetta C, Weber G, Cortinovis F, Calebiro D, Passoni A, Vigone MC, Beck-Peccoz P, Chiumello G, Persani L. A 7-year experience with low blood TSH cutoff levels for neonatal screening reveals an unsuspected frequency of congenital hypothyroidism (CH). Clin Endocrinol. 2009;71:739–745.Google Scholar
  23. 23.
    Korada SM, Pearce MS, Ward Platt MP, Avis E, Turner S, Wastelll H, Cheetham T. Difficulties in selecting an appropriate neonatal TSH screening threshold. Archives Dis Child. 2010;95;169–173.Google Scholar
  24. 24.
    Virtanen M, Mäenpää J, Pikkarainen L, Pitkänen L, Perheentupa J. Aetiology of congenital hypothyroidism in Finland. Acta Paediatrica Scandinavica. 1989;78:67–73.Google Scholar
  25. 25.
    Miyai K, Connelly JF, Foley TP, Irie M, Illig R, Lie SO, Morissette J, Nakajima H, Rochiccioli P, Walfish PG. An analysis of the variation of incidence of congenital dysgenic hypothyroidism in various countries. Endocrinol Japan. 1984;31: 77–81.Google Scholar
  26. 26.
    Nakamizo M, Toyabe S, Asami T, Akazawa K. Seasonality in the incidence of congenital hypothyroidism in Japan. J Paediatrics Child Health. 2005;41:390–394.Google Scholar
  27. 27.
    Miyai K, Inaoka K, Miyagi T. Further studies on episodic occurrence of congenital dysgenetic hypothyroidism in Osaka, Japan. Endocrine J. 2005;52:599–603.Google Scholar
  28. 28.
    Ouhoummane N, Levallois P, Gingras S. Thyroid function of newborns and exposure to chlorine dioxide by-products. Archives Environ Health. 2004;59:582–587.Google Scholar
  29. 29.
    Scinicariello F, Murray HE, Smith L, Wilbur S, Fowler BA. Genetic factors that might lead to different responses in individuals exposed to perchlorate. Environ Health Perspectives. 2005;113:1479–1484.Google Scholar
  30. 30.
    Miller SM, Green ML, Depinto JV, Hornbuckle KC. Results from the Lake Michigan mass balance study: concentrations and fluxes of atmospheric polychlorinated biphenyls and trans-nonachlor. Environ Sci Technol. 2001;35:278–85.PubMedCrossRefGoogle Scholar
  31. 31.
    Nagayama J, Kohno H, Kunisue K, Shimomura H, Tanabe S, Konishi S. Concentrations of organochlorine pollutants in mothers who gave birth to neonates with congenital hypothyroidism. Chemosphere. 2007;68:972–6.PubMedCrossRefGoogle Scholar
  32. 32.
    Nishiyama S, Mikeda T, Okada T, Nakamura K, Kotani T, Hishinuma A. Transient hypothyroidism or persistent hyperthyrotropinemia in neonates born to mothers with excessive iodine intake. Thyroid. 2004;14:1077–83.PubMedCrossRefGoogle Scholar
  33. 33.
    Kibirige MS, Hutchison S, Owen CJ, Delves HT. Prevalence of maternal dietary iodine insufficiency in the north east of England: implications for the fetus. Archives Dis Child. 2004;89:F436–9.CrossRefGoogle Scholar
  34. 34.
    Medda E, Olivieri A, Stazi MA, Grandolfo ME, Fazzini C, Baserga M, et al. Risk factors for congenital hypothyroidism: results of a population case-control study (1997–2003). Eur J Endocrinol. 2005;153:765–73.PubMedCrossRefGoogle Scholar
  35. 35.
    Oliveiri A, Medda E, De Angelis S, Valensise H, De Felice M, Fazzini C, Cascino I, Cordeddu V, Sorcini M, Stazi MA. High risk of congenital hypothyroidism in multiple pregnancies. J Clin Endocrinol Metabol. 2007;92:3141–7.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2011

Authors and Affiliations

  • Mark S. Pearce
    • 1
  • Richard J. Q. McNally
    • 1
  • Julie Day
    • 2
  • S. Murthy Korada
    • 3
  • Steve Turner
    • 4
  • Tim D. Cheetham
    • 3
    • 5
  1. 1.Institute of Health and Society, Sir James Spence Institute, Royal Victoria InfirmaryNewcastle UniversityNewcastle upon TyneUK
  2. 2.Department of Clinical BiochemistryUniversity Hospital of North DurhamDurhamUK
  3. 3.Department of Paediatric EndocrinologyRoyal Victoria InfirmaryNewcastle-upon-TyneUK
  4. 4.Department of Clinical BiochemistryRoyal Victoria InfirmaryNewcastle Upon TyneUK
  5. 5.Institute of Human Genetics, Centre for LifeNewcastle UniversityNewcastle-upon-TyneUK

Personalised recommendations