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Doubling in the use of thyroid hormone replacement therapy in Denmark: association to iodization of salt?

  • ENDOCRINE EPIDEMIOLOGY
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Abstract

Iodization of salt is an effective strategy to prevent iodine deficiency disorders. Recent studies, however, indicate that increasing the iodine intake in a population may give rise to an increased incidence of hypothyroidism, but the association has not been fully clarified. In Denmark, iodization of salt was initiated in 1998 because of mild-to-moderate iodine deficiency. The aim of this study was to evaluate the effect of the raised iodine intake on the nationwide incident use of thyroid hormone replacement therapy (levothyroxine) to treat hypothyroidism. Data on all use of levothyroxine was extracted from the Register of Medicinal Product Statistics during the period 1995–2009 and linked to other nationwide registers by use of the Danish identification number. Persons with previous thyroid surgery were excluded. In the studied period 71,565 incident users were identified. The incidence rate increased 75% in the moderately iodine deficient region (72.2 incident users/100,000 person-years in 1997 to 126.6 in 2008) and 87% in the mildly deficient region (86.9–162.9). When stratified by sex and age-group (00–39, 40–64, 65+) the largest relative increase was seen among women in the youngest age-group, where more than a doubling was seen. The mechanisms behind the increase may be a result of iodine-induced hypothyroidism, although a higher diagnostic activity with regard to thyroid dysfunction and intensified treatment of subclinical hypothyroidism may also play a role. Our findings stress the need for caution when initiating iodine fortification programs to keep the intake within the optimal range, and the need for continuous monitoring.

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Abbreviations

DanThyr:

The Danish Investigation of Iodine Intake and Thyroid Diseases.

ATC:

Anatomic therapeutical chemical.

DDD:

Defined daily dose.

ID:

Iodine deficiency.

CI:

Confidence interval.

References

  1. Hetzel BS, Dunn JT. The iodine deficiency disorders: their nature and prevention. Annu Rev Nutr. 1989;9:21–38.

    Article  PubMed  CAS  Google Scholar 

  2. Knudsen N, Bulow I, Jorgensen T, Laurberg P, Ovesen L, Perrild H. Comparative study of thyroid function and types of thyroid dysfunction in two areas in Denmark with slightly different iodine status. Eur J Endocrinol. 2000;143(4):485–91.

    Article  PubMed  CAS  Google Scholar 

  3. Laurberg P, Bulow PI, Knudsen N, Ovesen L, Andersen S. Environmental iodine intake affects the type of nonmalignant thyroid disease. Thyroid. 2001;11(5):457–69.

    Article  PubMed  CAS  Google Scholar 

  4. Teng W, Shan Z, Teng X, Guan H, Li Y, Teng D, et al. Effect of iodine intake on thyroid diseases in China. N Engl J Med. 2006;354(26):2783–93.

    Article  PubMed  CAS  Google Scholar 

  5. Tsatsoulis A, Johnson EO, Andricula M, Kalogera C, Svarna E, Spyroy P, et al. Thyroid autoimmunity is associated with higher urinary iodine concentrations in an iodine-deficient area of Northwestern Greece. Thyroid. 1999;9(3):279–83.

    Article  PubMed  CAS  Google Scholar 

  6. Szabolcs I, Podoba J, Feldkamp J, Dohan O, Farkas I, Sajgo M, et al. Comparative screening for thyroid disorders in old age in areas of iodine deficiency, long-term iodine prophylaxis and abundant iodine intake. Clin Endocrinol (Oxf). 1997;47(1):87–92.

    Article  CAS  Google Scholar 

  7. Zimmermann MB, Moretti D, Chaouki N, Torresani T. Introduction of iodized salt to severely iodine-deficient children does not provoke thyroid autoimmunity: a one-year prospective trial in northern Morocco. Thyroid. 2003;13(2):199–203.

    Article  PubMed  CAS  Google Scholar 

  8. Benmiloud M, Chaouki ML, Gutekunst R, Teichert HM, Wood WG, Dunn JT. Oral iodized oil for correcting iodine deficiency: optimal dosing and outcome indicator selection. J Clin Endocrinol Metab. 1994;79(1):20–4.

    Article  PubMed  CAS  Google Scholar 

  9. Tajiri J, Higashi K, Morita M, Umeda T, Sato T. Studies of hypothyroidism in patients with high iodine intake. J Clin Endocrinol Metab. 1986;63(2):412–7.

    Article  PubMed  CAS  Google Scholar 

  10. Harach HR, Escalante DA, Day ES. Thyroid cancer and thyroiditis in Salta, Argentina: a 40-yr study in relation to iodine prophylaxis. Endocr Pathol. 2002;13(3):175–81.

    Article  PubMed  Google Scholar 

  11. Rose NR, Bonita R, Burek CL. Iodine: an environmental trigger of thyroiditis. Autoimmun Rev. 2002;1(1–2):97–103.

    Article  PubMed  CAS  Google Scholar 

  12. Cerqueira C, Knudsen N, Ovesen L, Perrild H, Rasmussen LB, Laurberg P, et al. Association of iodine fortification with incident use of antithyroid medication–a Danish Nationwide study. J Clin Endocrinol Metab. 2009;94(7):2400–5.

    Article  PubMed  CAS  Google Scholar 

  13. Cerqueira C, Knudsen N, Ovesen L, Laurberg P, Perrild H, Rasmussen LB, et al. Nationwide trends in surgery and radioiodine treatment for benign thyroid disease during iodization of salt. Eur J Endocrinol. 2010;162(4):755–62.

    Article  PubMed  CAS  Google Scholar 

  14. Pedersen KM, Laurberg P, Nohr S, Jorgensen A, Andersen S. Iodine in drinking water varies by more than 100-fold in Denmark. Importance for iodine content of infant formulas. Eur J Endocrinol. 1999;140(5):400–3.

    Article  PubMed  CAS  Google Scholar 

  15. Rasmussen LB, Ovesen L, Bulow I, Jorgensen T, Knudsen N, Laurberg P, et al. Dietary iodine intake and urinary iodine excretion in a Danish population: effect of geography, supplements and food choice. Br J Nutr. 2002;87(1):61–9.

    Article  PubMed  CAS  Google Scholar 

  16. World Health Organization, The United Nations Children′s Fund, International council for the control of iodine deficiency disorders. Assessment of iodine deficiency disorders and monitoring their elimination 3rd ed. Geneva. World Health Organization; 2008.

  17. Pedersen KM, Nohr SB, Laurberg P. [Iodine intake in Denmark]. Ugeskr Laeger. 1997;159(15):2201–6.

    PubMed  CAS  Google Scholar 

  18. Rasmussen LB, Carle A, Jorgensen T, Knudsen N, Laurberg P, Pedersen IB, et al. Iodine intake before and after mandatory iodization in Denmark: results from the Danish Investigation of Iodine Intake and Thyroid Diseases (DanThyr) study Br J Nutr. 2008;100(1):166–73.

    Google Scholar 

  19. Bulow PI, Knudsen N, Jorgensen T, Perrild H, Ovesen L, Laurberg P. Large differences in incidences of overt hyper- and hypothyroidism associated with a small difference in iodine intake: a prospective comparative register-based population survey. J Clin Endocrinol Metab. 2002;87(10):4462–9.

    Article  Google Scholar 

  20. Teng X, Shi X, Shan Z, Jin Y, Guan H, Li Y, et al. Safe range of iodine intake levels: a comparative study of thyroid diseases in three women population cohorts with slightly different iodine intake levels. Biol Trace Elem Res. 2008;121(1):23–30.

    Article  PubMed  CAS  Google Scholar 

  21. Bülow Pedersen I, Knudsen N, Carle A, Vejbjerg P, Perrild H, Jorgensen T, et al. Even a cautious iodization program bringing iodine intake to a low recommended level is associated with an increase in the prevalence of TPO-Ab and Tg-Ab in the population. 14th International Thyroid Congress—800; 2010.

  22. Pedersen IB, Laurberg P, Knudsen N, Jorgensen T, Perrild H, Ovesen L, et al. An increased incidence of overt hypothyroidism after iodine fortification of salt in Denmark: a prospective population study. J Clin Endocrinol Metab. 2007;92(8):3122–7.

    Article  PubMed  CAS  Google Scholar 

  23. McDermott MT, Ridgway EC. Subclinical hypothyroidism is mild thyroid failure and should be treated. J Clin Endocrinol Metab. 2001;86(10):4585–90.

    Article  PubMed  CAS  Google Scholar 

  24. Gharib H, Tuttle RM, Baskin HJ, Fish LH, Singer PA, McDermott MT. Subclinical thyroid dysfunction: a joint statement on management from the American association of clinical endocrinologists, the American thyroid association, and the endocrine society. J Clin Endocrinol Metab. 2005;90(1):581–5.

    Article  PubMed  CAS  Google Scholar 

  25. Hak AE, Pols HA, Visser TJ, Drexhage HA, Hofman A, Witteman JC. Subclinical hypothyroidism is an independent risk factor for atherosclerosis and myocardial infarction in elderly women: the Rotterdam study. Ann Intern Med. 2000;132(4):270–8.

    PubMed  CAS  Google Scholar 

  26. Canturk Z, Cetinarslan B, Tarkun I, Canturk NZ, Ozden M. Lipid profile and lipoprotein (a) as a risk factor for cardiovascular disease in women with subclinical hypothyroidism. Endocr Res. 2003;29(3):307–16.

    Article  PubMed  CAS  Google Scholar 

  27. Monzani F, Del Guerra P, Caraccio N, Pruneti CA, Pucci E, Luisi M, et al. Subclinical hypothyroidism: neurobehavioral features and beneficial effect of L-thyroxine treatment. Clin Investig. 1993;71(5):367–71.

    PubMed  CAS  Google Scholar 

  28. Surks MI, Ortiz E, Daniels GH, Sawin CT, Col NF, Cobin RH, et al. Subclinical thyroid disease: scientific review and guidelines for diagnosis and management. JAMA. 2004;291(2):228–38.

    Article  PubMed  CAS  Google Scholar 

  29. Chu JW, Crapo LM. The treatment of subclinical hypothyroidism is seldom necessary. J Clin Endocrinol Metab. 2001;86(10):4591–9.

    Article  PubMed  CAS  Google Scholar 

  30. Karmisholt JS, Laurberg P. [Subclinical hypothyroidism–a condition that must be treated?]. Ugeskr Laeger. 2006;168(37):3113–6.

    PubMed  Google Scholar 

  31. Bonnema SJ, Bennedbaek FN, Wiersinga WM, Hegedus L. Management of the nontoxic multinodular goitre: a European questionnaire study. Clin Endocrinol (Oxf). 2000;53(1):5–12.

    Article  CAS  Google Scholar 

  32. Vejbjerg P, Knudsen N, Perrild H, Carle A, Laurberg P, Pedersen IB, et al. Effect of a mandatory iodization program on thyroid gland volume based on individuals’ age, gender, and preceding severity of dietary iodine deficiency: a prospective, population-based study. J Clin Endocrinol Metab. 2007;92(4):1397–401.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

This study was part of The Danish Investigation on Iodine Intake and Thyroid Diseases (DanThyr), which is supported by grants from the Danish Medical Foundation, the 1991 Pharmacy Foundation, North Jutland County Research Foundation, Tømmerhandler Wilhelm Bangs Foundation, Copenhagen Hospital Corporation Research Foundation, The Danish Food Industry Agency, and the Danish Agency for Science Technology and Innovation (grant number 2101-06-0065).

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The authors declare that no competing financial interests exist.

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Correspondence to Charlotte Cerqueira.

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Cerqueira, C., Knudsen, N., Ovesen, L. et al. Doubling in the use of thyroid hormone replacement therapy in Denmark: association to iodization of salt?. Eur J Epidemiol 26, 629–635 (2011). https://doi.org/10.1007/s10654-011-9590-5

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  • DOI: https://doi.org/10.1007/s10654-011-9590-5

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