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Horm Metab Res 2011; 43(5): 349-354
DOI: 10.1055/s-0031-1273699
Humans, Clinical

© Georg Thieme Verlag KG Stuttgart · New York

Evidence for a more Pronounced Effect of Genetic Predisposition than Environmental Factors on Goitrogenesis by a Case Control Study in an Area with Low Normal Iodine Supply

J. Singer1 , M. Eszlinger1 , J. Wicht1 , R. Paschke1
  • 1Department of Endocrinology and Nephrology, University of Leipzig, Leipzig, Germany
Further Information

Publication History

received 21.12.2010

accepted 10.02.2011

Publication Date:
16 March 2011 (online)

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Abstract

Family and twin studies suggest a genetic predisposition for euthyroid goiters. However, iodine deficiency and smoking are important exogenous factors for goiter development. We investigated goiter predisposition by a matched case control study in a region with recently documented low normal iodine supply. A sum of 376 patients were included in the study. We matched 188 patients with euthyroid/subclinically hyperthyroid goiter (TSH 4.20–0.05 mU/l) with 188 euthyroid controls without thyroid enlargement for age and gender. Thyroid ultrasound was performed in all patients, whereby 50.5% of patients with goiters showed a positive family history for goiter. In contrast, only 25% of control patients had a positive family history (p<0.001; OR=3.1). Patients with goiters had a significantly higher proportion of parents (p<0.001; OR=3.6) or siblings (p=0.004; OR=2.5) with goiters. Children of parents with goiters showed a 2.7-fold increased risk for goiter development (goiter prevalence 73.3%). Patients with a positive goiter family history had a 4.1-fold increased goiter risk (p<0.001). The contribution of smoking, obesity, and pregnancies to goiter development was less important than the genetic predisposition (OR=1.7; p=0.06; OR=1.67; p=0.13; OR=0.8; p=0.56). In a region with low normal iodine supply, the significantly higher rate of positive family histories in patients with goiters as compared to the matched controls as well as the increased goiter prevalence in children of parents with goiters indicate the importance of genetic factors in goiter development.

Key words

goiter - risk factors - susceptibility - case-control study

References

  • 1 Brix TH, Hegedus L. Genetic and environmental factors in the aetiology of simple goitre.  Ann Med. 2000;  32 153-156
    Google Scholar
  • 2 Knudsen N, Laurberg P, Perrild H, Bulow I, Ovesen L, Jorgensen T. Risk factors for goiter and thyroid nodules.  Thyroid. 2002;  12 879-888
    Google Scholar
  • 3 Brix TH, Hansen PS, Kyvik KO, Hegedus L. Cigarette smoking and risk of clinically overt thyroid disease: a population-based twin case-control study.  Arch Intern Med. 2000;  160 661-666
    Google Scholar
  • 4 Knudsen N, Bulow I, Laurberg P, Ovesen L, Perrild H, Jorgensen T. Association of tobacco smoking with goiter in a low-iodine-intake area.  Arch Inter Med. 2002;  162 439-443
    Google Scholar
  • 5 Völzke H, Schwahn C, Kohlmann T, Kramer A, Robinson DM, John U, Meng W. Risk factors for goiter in a previously iodine-deficient region.  Exp Clin Endocrinol Diabetes. 2005;  113 507-515
    Google Scholar
  • 6 Sari R, Balci MK, Altunbas H, Karayalcin U. The effect of body weight and weight loss on thyroid volume and function in obese women.  Clin Endocrinol. 2003;  59 258-262
    Google Scholar
  • 7 Berghout A, Endert E, Ross A, Hogerzeil HV, Smits NJ, Wiersinga WM. Thyroid function and thyroid size in normal pregnant women living in an iodine replete area.  Clin Endocrinol. 1994;  41 375-379
    Google Scholar
  • 8 Glinoer D. What happens to the normal thyroid during pregnancy?.  Thyroid. 1999;  9 631-635
    Google Scholar
  • 9 Knudsen N, Bulow I, Laurberg P, Ovesen L, Perrild H, Jorgensen T. Parity is associated with increased thyroid volume solely among smokers in an area with moderate to mild iodine deficiency.  Europ J Endocrinol. 2002;  146 39-43
    Google Scholar
  • 10 Chandra AK, Mukhopadhyay S, Lahari D, Tripathy S. Goitrogenic content of Indian cyanogenic plant foods and their in vitro anti-thyroidal activity.  Indian J Med Res. 2004;  119 180-185
    Google Scholar
  • 11 Surks MI, Sievert R. Drugs and thyroid function.  New Eng J Med. 1995;  333 1688-1694
    Google Scholar
  • 12 Hampel R, Külberg T, Klein K, Jerichow JU, Pichmann EG, Clausen V, Schmidt I. Goiter incidence in Germany is greater than previously suspected.  Med Klin. 1995;  90 324-329
    Google Scholar
  • 13 Völzke H, Lüdemann J, Robinson DM, Spieker KW, Schwahn C, Kramer A, John U, Meng W. The prevalence of undiagnosed thyroid disorders in a previously iodine-deficient area.  Thyroid. 2003;  13 803-810
    Google Scholar
  • 14 Krohn K, Fuhrer D, Bayer Y, Eszlinger M, Brauer V, Neumann S, Paschke R. Molecular pathogenesis of euthyroid and toxic multinodular goiter.  Endocr Rev. 2005;  26 504-524
    Google Scholar
  • 15 Malamos B, Koutras DA, Kostamis P, Kralios AC, Rigopoulos G, Zerefos N. Endemic goiter in Greece: epidemiologic and genetic studies.  J Clin Endocrinol Metab. 1966;  26 688-695
    Google Scholar
  • 16 Hadjidakis SG, Koutras DA, Daikos GK. Endemic goitre in Greece: Familiy studies.  J Med Genet. 1964;  38 82-87
    Google Scholar
  • 17 Heimann P. Familial incidence of thyroid disease and anamnestic incidence of pubertal struma in 449 consecutive struma patients.  Acta Med Scand. 1966;  179 113-119
    Google Scholar
  • 18 Malamos B, Koutras DA, Kostamis P, Rigopoulos GA, Zerefos NS, Yataganas XA. Endemic goitre in Greece: a study of 379 twin pairs.  J Med Genet. 1967;  4 16-18
    Google Scholar
  • 19 Abuye C, Omwega AM, Imungi JK. Familial tendency and dietary association of goitre in Goma-Gofa, Ethiopia.  East African Med J. 1999;  76 447-451
    Google Scholar
  • 20 Brix TH, Kyvik KO, Hegedus L. Major role of genes in the etiology of simple goiter in females: a population-based twin study.  J Clin Endocrinol Metab. 1999;  84 3071-3075
    Google Scholar
  • 21 Hansen PS, Brix TH, Bennedbaek FN, Bonnema SJ, Kyvik KO, Hegedus L. Genetic and environmental causes of individual differences in thyroid size: a study of healthy Danish twins.  J Clin Endocrinol Metab. 2004;  89 2071-2077
    Google Scholar
  • 22 Bignell GR, Canzian F, Shayeghi M, Stark M, Shugart YY, Biggs P, Mangion J, Hamoudi R, Rosenblatt J, Buu P, Sun S, Stoffer SS, Goldgar DE, Romeo G, Houlston RS, Narod SA, Stratton MR, Foulkes WD. Familial nontoxic multinodular thyroid goiter locus maps to chromosome 14q but does not account for familial nonmedullary thyroid cancer.  Am J Hum Genet. 1997;  61 1123-1130
    Google Scholar
  • 23 Neumann S, Willgerodt H, Ackermann F, Reske A, Jung M, Reis A, Paschke R. Linkage of familial euthyroid goiter to the multinodular goiter-1 locus and exclusion of the candidate genes thyroglobulin, thyroperoxidase, and Na+/I− symporter.  J Clin Endocrinol Metab. 1999;  84 3750-3756
    Google Scholar
  • 24 Capon F, Tacconelli A, Giardina E, Sciacchitano S, Bruno R, Tassi V, Trischitta V, Filetti S, Dallapiccola B, Novelli G. Mapping a dominant form of multinodular goiter to chromosome Xp22.  Am J Hum Genet. 2000;  67 1004-1007
    Google Scholar
  • 25 Bayer Y, Neumann S, Meyer B, Rüschendorf F, Reske A, Brix T, Hegedüs L, Langer P, Nürnberg P, Paschke R. Genome-wide linkage analysis reveals evidence for four new susceptibility loci for familial euthyroid goiter.  J Clin Endocrinol Metab. 2004;  89 4044-4052
    Google Scholar
  • 26 Brain WR. Heredity in simple goitre.  Quart J Med. 1927;  20 303-319
    Google Scholar
  • 27 Neumann S, Bayer Y, Reske A, Tajtakova M, Langer P, Paschke R. Further indications for genetic heterogeneity of euthyroid familial goiter.  J Mol Med. 2003;  81 736-745
    Google Scholar
  • 28 Böttcher Y, Eszlinger M, Tönjes A, Paschke R. The genetics of euthyroid famial goiter.  Trends Endocrinol Metab. 2005;  16 314-319
    Google Scholar
  • 29 Brauer VF, Brauer WH, Führer D, Paschke R. Iodine nutrition, nodular thyroid disease, and urinary iodine excretion in a German university study population.  Thyroid. 2005;  15 364-370
    Google Scholar
  • 30 Thamm M, Ellert U, Thierfelder W, Liesenkötter KP, Völzke H. Iodine intake in Germany. Results of iodine monitoring in the German Health Interview and Examination Survey for Children and Adolescents (KiGGS)].  Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz. 2007;  50 744-749
    Google Scholar
  • 31 Bähre M, Hilgers R, Lindemann C, Emrich D. Thyroid autonomy: sensitive detection in vivo and estimation of its functional relevance using quantified high-resolution scintigraphy.  Acta Endocrinol (Copenh). 1988;  117 145-153
    Google Scholar
  • 32 Krohn K, Wohlgemuth S, Gerber H, Paschke R. Hot microscopic areas of iodine-deficient euthyroid goitres contain constitutively activating TSH receptor mutations.  J Pathol. 2000;  192 37-42
    Google Scholar
  • 33 Gutekunst R, Becker W, Hehrmann R, Olbricht T, Pfannenstiel P. Ultrasonic diagnosis of the thyroid gland.  Dtsch Med Wochenschr. 1988;  113 1109-1112
    Google Scholar
  • 34 Brix TH, Hansen PS, Knudsen GPS, Kringen MK, Kyvik KO, Orstavik KH, Hegedüs L. No link between X chromosome inactivation pattern and simple goiter in females: evidence from a twin study.  Thyroid. 2009;  19 165-169
    Google Scholar
  • 35 Christensen K, Fogh-Andersen P. Etiological subgroups in non-syndromic isolated cleft palate. A genetic-epidemiological study of 52 Danish birth cohorts.  Clin Genet. 1994;  46 329-335
    Google Scholar
  • 36 Buselmaier W, Tariverdian G. Humangenetik.. Heidelberg: Springer Medizin Verlag; 2007
    Google Scholar
  • 37 Knudsen N, Bulow I, Laurberg P, Perrild H, Ovesen L, Jorgensen T. Low goitre prevalence among users of oral contrazeptives in a population sample of 3 712 women.  Clin Endocrinol. 2002;  57 71-76
    Google Scholar

Correspondence

R. Paschke

Department of Endocrinology

and Nephrology

University of Leipzig

Liebigstraße 20

04103 Leipzig

Germany

Phone: +49/341/971 3201

Fax: +49/341/971 3209

Email: Ralf.Paschke@medizin.uni-leipzig.de

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