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
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
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
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
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
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
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
8
Glinoer D.
What happens to the normal thyroid during pregnancy?.
Thyroid.
1999;
9
631-635
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
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
11
Surks MI, Sievert R.
Drugs and thyroid function.
New Eng J Med.
1995;
333
1688-1694
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
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
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
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
16
Hadjidakis SG, Koutras DA, Daikos GK.
Endemic goitre in Greece: Familiy studies.
J Med Genet.
1964;
38
82-87
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
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
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
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
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
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
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
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
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
26
Brain WR.
Heredity in simple goitre.
Quart J Med.
1927;
20
303-319
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
28
Böttcher Y, Eszlinger M, Tönjes A, Paschke R.
The genetics of euthyroid famial goiter.
Trends Endocrinol Metab.
2005;
16
314-319
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
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
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
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
33
Gutekunst R, Becker W, Hehrmann R, Olbricht T, Pfannenstiel P.
Ultrasonic diagnosis of the thyroid gland.
Dtsch Med Wochenschr.
1988;
113
1109-1112
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
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
36 Buselmaier W, Tariverdian G. Humangenetik.. Heidelberg: Springer Medizin Verlag; 2007
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
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