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Pedersen, Laurberg
Increase in incidence of hyperthyroidism predominantly occurs in young people after iodine fortification of salt in Denmark.Pedersen IB, Laurberg P, Knudsen N, Jorgensen T, Perrild H, Ovesen L, Rasmussen LB. J Clin Endocrinol Metab. 2006 Oct;91(10):3830-4. Epub 2006 Jul 18.
"CONTEXT: To prevent goiter and nodular hyperthyroidism, iodine fortification (IF) of salt was introduced in Denmark in 1998. We prospectively registered all new cases of overt hyperthyroidism in two areas of Denmark before and for the first 6 yr after iodine fortification.
METHODS: We used a computer-based register of all new cases of hyperthyroidism in two population subcohorts with moderate iodine deficiency (Aalborg, n = 310,124) and mild iodine deficiency (Copenhagen, n = 225,707), respectively. Data were obtained 1) before IF (1997-1998); 2) during voluntary IF (1999-2000); 3) during the early (2001-2002) period of mandatory IF; and 4) during the late (2003-2004) period with mandatory IF.
RESULTS: The overall incidence rate of hyperthyroidism increased [baseline, 102.8/100,000/year; voluntary IF, 122.8; early mandatory IF, 140.7; late mandatory IF, 138.7 (P for trend <0.001)]. Hyperthyroidism increased in both sexes (P < 0.001) and in all age groups: 0-19, 20-39, 40-59, and 60+ yr (P for trend <0.001). The increase was relatively highest in young adults aged 20-39 yr: late mandatory IF (percent increase from baseline), age 20-39, 160%, P < 0.001; age 40-59, 29%, P < 0.01; age 60+ yr, 13%, P = not significant.
CONCLUSION: Even a cautious iodization of salt results in an increase in the incidence rate of hyperthyroidism. Contrary to current concepts, many of the new cases were observed in young subjects, and are presumably of autoimmune origin. Furthermore, monitoring is expected to show a decrease in the number of elderly subjects suffering from nodular hyperthyroidism."
The Danish investigation on iodine intake and thyroid disease, DanThyr: status and perspectives.Laurberg P, Jorgensen T, Perrild H, Ovesen L, Knudsen N, Pedersen IB, Rasmussen LB, Carle A, Vejbjerg P. Eur J Endocrinol. 2006 Aug;155(2):219-28. [abstract only]
"OBJECTIVE: Denmark was an area of iodine deficiency, and mandatory iodine fortification of table salt and salt in bread (13 p.p.m. iodine) was initiated in 2000/2001. The Danish investigation on iodine intake and thyroid disease (DanThyr) is the monitoring of the iodine fortification program.
DESIGN AND METHODS: DanThyr consists of three main parts: a study of population cohorts initialized before (n=4649) and after (n=3570) iodization of salt, a prospective identification of incident cases of overt hyper- and hypothyroidism in a population of around 550,000 people since 1997, and compilation of data from the national registers on the use of thyroid medication, thyroid surgery, and radioiodine therapy. Studies were carried-out in parallel in subcohorts living in areas with differences in iodine content of ground water.
RESULTS: The study showed profound effects of even small differences in iodine intake level on the prevalence of goiter, nodules, and thyroid dysfunction. Mild and moderate iodine deficiency was associated with a decrease in serum TSH with age. Other environmental factors were also important for goiter development (increase in risk, smoking and pregnancy; decrease in risk, oral contraception and alcohol consumption), and the individual risk depended on the genetic background. Environmental factors had only a minor influence on the prevalence of thyroid autoantibodies in the population. There were more cases of overt hypothyroidism in mild than in moderate iodine deficiency caused by a 53% higher incidence of spontaneous (presumably autoimmune) hypothyroidism. On the other hand, there were 49% more cases of overt hyperthyroidism in the area with moderate iodine deficiency. The cautious iodine fortification program, aiming at an average increase in iodine intake of 50 mug/day has been associated with a 50% increase in incidence of hyperthyroidism in the area with the most severe iodine deficiency. The incidence is expected to decrease in the future, but there may be more cases of Graves' hyperthyroidism in young people.
CONCLUSION: A number of environmental factors influence the epidemiology of thyroid disorders, and even relatively small abnormalities and differences in the level of iodine intake of a population have profound effects on the occurrence of thyroid abnormalities. Monitoring and adjustment of iodine intake in the population is an important part of preventive medicine."
Large differences in incidences of overt hyper- and hypothyroidism associated with a small difference in iodine intake: a prospective comparative register-based population survey.Pedersen IB, Knudsen N, Jorgensen T, Perrild H, Ovesen L, Laurberg P. J Clin Endocrinol Metab. 2002 Oct;87(10):4462-9.
"Around 3-4 billion people in the world are covered by iodine supplementation programs to prevent developmental brain damage and other iodine deficiency (ID) disorders. Mild ID is associated with more hyperthyroidism and less hypothyroidism in the population than a high iodine intake. Knowledge of the iodine intake levels where the shifts in incidences occur is important for planning of iodine supplementation programs. A computer-based register linked to thyroid diagnostic laboratories was used to continuously identify all new cases of overt hyper- and hypothyroidism in two population cohorts with moderate and mild ID, respectively (Aalborg, n = 310,124; urinary iodine, 45 micro g/liter; and Copenhagen, n = 225,707; urinary iodine, 61 micro g/liter). The investigation was initiated before iodization of salt in Denmark and was part of the monitoring program. In 1997-1998, the incidence rate of overt hyperthyroidism was high in the area with the lowest iodine intake (92.9/100,000 per year) compared with the area with only mild ID (65.4/100,000 per year). Standardized rate ratio was 1.49, and 95% confidence interval was 1.22-1.81. The opposite relationship was present for overt hypothyroidism (moderate ID, 26.5/100,000 per year; mild ID, 40.1/100,000 per year; standardized rate ratio, 0.73; 95% confidence interval, 0.55-0.97). The different incidence rates were confirmed during each of the two following years. The results of this prospective investigation of the incidence of overt hyper- and hypothyroidism suggest that iodine supplementation of a population may increase the incidence of overt hypothyroidism, even if the population is moderately iodine-deficient. In such a population, the increase in risk of hypothyroidism should be weighed against the risk of ID disorders such as hyperthyroidism due to multinodular toxic goiter. The optimal level of iodine intake to prevent thyroid disease may be a relatively narrow range around the recommended daily iodine intake of 150 micro g."
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