The Danish investigation on iodine intake and thyroid disease (DanThyr): history and implications

Abstract

Due to mild-to-moderate iodine deficiency in Denmark, health authorities initiated a voluntary iodine fortification (IF) program in 1998, which became mandatory in 2000. In line with recommendations from the World Health Organization, the Danish investigation on iodine intake and thyroid disease (DanThyr) was established to monitor the effect on thyroid health and disease. The program involved different study designs and followed two Danish sub-populations in the years before IF and up till 20 years after. Results showed that the IF was successfully implemented and increased the level of iodine intake from mild-moderate iodine deficiency to low adequacy. The level of thyroglobulin and thyroid volume decreased following IF, and there was an indication of fewer thyroid nodules. The incidence of hyperthyroidism increased transiently following IF but subsequently decreased below the pre-fortification level. Conversely, thyroid-stimulating hormone levels and the prevalence of thyroid autoimmunity increased along with an increase in the incidence of hypothyroidism. These trends were mirrored in the trends in treatments for thyroid disease. Most differences in thyroid health and disease between regions with different iodine intake levels before IF attenuated. This review illustrates the importance of a monitoring program to detect both beneficial and adverse effects and exemplifies how a monitoring program can be conducted when a nationwide health promotion program - as IF - is initiated.

Keywords: epidemiology; iodine; public health; thyroid disease.

Figure 1

Map of Denmark. Crudely, western Denmark had moderate ID before IF, and eastern Denmark had mild ID before IF. Bread from bakeries was analyzed in samples from Aarhus in western Denmark and Copenhagen in eastern Denmark (squares). The cohort studies and laboratory studies were conducted in and around the city of Aalborg in western Denmark and in Copenhagen in eastern Denmark (circles). The nationwide register studies stratified the population into west and east as illustrated by the dashed line. ID, iodine deficiency; IF, iodine fortification.

Figure 2

Overview of the four study designs and timing of these in the Danish Investigation on Iodine Intake and Thyroid Disease (DanThyr). ppm, parts per million. The DanThyr studies monitored the effects of the Danish iodine fortification through four different study designs: (1) analyses of iodine content in salt, bread, and milk monitored the implementation of IF and iodine sources, (2) two cross-sectional cohort studies in 1997–1998 and 2004–2005, with a follow-up of the first in 2008–2010, comprised questionnaires (on diseases, medication, treatments, and lifestyle), thyroid ultrasound, and blood- and urine samples. The studies were conducted simultaneously in Aalborg in western Denmark and in Copenhagen in eastern Denmark. (3) Laboratory studies collected results from all thyroid function tests ordered by general practitioners or in hospitals continuously from 1997 to 2018 in and around Aalborg in western Denmark and continuously from 1997 to 2008 in Copenhagen in eastern Denmark. (4) National register studies examined trends in treatments for thyroid disease (medication, surgery, and radioiodine) continuously from 1997 to 2015. Voluntary IF with 8 ppm was introduced in 1998, and mandatory IF with 13 ppm in 2000. Western Denmark had moderate iodine deficiency before iodine fortification, and eastern Denmark had mild iodine deficiency before iodine fortification.

Figure 3

Main results from the DanThyr laboratory studies (32, 59). SIR, standardized incidence rates; ID, iodine deficiency; PY person-years. Development in standardized incidence rates of thyrotoxicosis (A) and hypothyroidism (B) in the laboratory studies. Error bars indicate the 95% CI. Asterix (*) indicates SIRs are statistically significantly different from the SIRs in 1997–mid 1998. Voluntary IF with 8 ppm was introduced in 1998, and mandatory IF with 13 ppm in 2000. Western Denmark had moderate iodine deficiency before iodine fortification, and eastern Denmark had mild iodine deficiency before iodine fortification. Originally published in refs. (59) and (32).