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Iodine intake as a determinant of thyroid disorders in populations

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Depending on the availability of iodine, the thyroid gland is able to enhance or limit the use of iodine for thyroid hormone production. When compensation fails, as in severely iodine-deficient populations, hypothyroidism and developmental brain damage will be the dominating disorders. This is, out of all comparison, the most serious association between disease and the level of iodine intake in a population.

In less severe iodine deficiency, the normal thyroid gland is able to adapt and keep thyroid hormone production within the normal range. However, the prolonged thyroid hyperactivity associated with such adaptation leads to thyroid growth, and during follicular cell proliferation there is a tendency to mutations leading to multifocal autonomous growth and function.

In populations with mild and moderate iodine deficiency, such multifocal autonomous thyroid function is a common cause of hyperthyroidism in elderly people, and the prevalence of thyroid enlargement and nodularity is high. The average serum TSH tends to decrease with age in such populations caused by the high frequency of autonomous thyroid hormone production.

On the other hand, epidemiological studies have shown that hypothyroidism is more prevalent in populations with a high iodine intake. Probably, this is also a complication to thyroid adaptation to iodine intake. Many thyroid processes are inhibited when iodine intake becomes high, and the frequency of apoptosis of follicular cells becomes higher. Abnormal inhibition of thyroid function by high levels of iodine is especially common in people affected by thyroid autoimmunity (Hashimoto's thyroiditis).

In populations with high iodine intake, the average serum thyroid-stimulating hormone (TSH) tends to increase with age. This phenomenon is especially pronounced in Caucasian populations with a genetically determined high tendency to thyroid autoimmunity. A small tendency to higher serum TSH may be observed already when iodine intake is brought from mildly deficient to adequate, but there is at present no evidence that slightly elevated serum TSH in elderly people leads to an increase in morbidity and mortality.

Conclusion: Even minor differences in iodine intake between populations are associated with differences in the occurrence of thyroid disorders. Both iodine intake levels below and above the recommended interval are associated with an increase in the risk of disease in the population. Optimally, iodine intake of a population should be kept within a relatively narrow interval where iodine deficiency disorders are prevented, but not higher. Monitoring and adjusting of iodine intake in a population is an important part of preventive medicine.

Section snippets

The spectrum of diseases caused by iodine deficiency and iodine excess

The classical understanding of the relationship between iodine intake and disease was that people would develop disease if their iodine intake were below a certain limit.5 Because natural foods and beverages contained little iodine in many parts of the world, many populations were affected by iodine deficiency disorders.6 On the other hand, even intake of relatively large amounts of iodine were considered well tolerated, with toxicity seen only if intakes were many-fold higher than the

Brain damage from low iodine intake

Table 1 illustrates the spectrum of disorders that somehow depends on the iodine intake level of the population.

By far, the most serious defect that may be associated with abnormal iodine intake is developmental brain damage caused by severe iodine deficiency.11 In foetal life, brain development takes place over a long period, starting as early as a few weeks after conception and continuing during the first years after birth.12

The iodine necessary for thyroid hormone production by the mother,

Level of iodine intake in pregnant women associated with risk of brain damage

Many studies have shown that severe iodine deficiency is associated with a high frequency of goitre and hypothyroidism in a population, and that frank cretinism and less severe intellectual impairment may be common in such populations5, 11 (Table 1).

The description of iodine deficiency as severe, moderate or mild was based on compilations of data such as illustrated in Fig. 1. It is the association between the frequency of goitre and the level of urinary iodine excretion in various population

The shift from excess hypothyroidism to excess hyperthyroidism associated with iodine deficiency

Severe iodine deficiency may cause excessive hypothyroidism in a population because of lack of substrate for thyroid hormone production. However, mild-to-moderate iodine deficiency is not associated with hypothyroidism. On the contrary, it is associated with excess hyperthyroidism in the population.32 Apparently, at moderately low levels of iodine intake, the thyroid gland is able to compensate for this and keep thyroid hormone production normal. However, as discussed below, the price of

Iodine intake and the prevalence of circulating thyroid autoantibodies

In many people, the thyroid gland is not tolerated well by the immune system, as illustrated by the frequent finding of lymphocytic infiltration of the gland. In autopsy studies of white (Caucasians) and black Americans as well as British white and Japanese, Okayasu et al.44, 45 demonstrated lymphocytic thyroid infiltration in about 40% of white females over 20 years of age and up to 50% in elderly women living in the USA and in the UK. This was around 20% of the white males. In the black

Hypothyroidism in populations with a high iodine intake

It is well established that individual patients with autoimmune thyroiditis may develop hypothyroidism when exposed to excess iodine.54 Considering the very frequent occurrence of thyroid autoimmunity in the population, it would be expected that a high iodine intake would be associated with a high frequency of subclinical (with elevated serum TSH but a free T4 estimate within the reference range) and overt (elevated TSH and low estimate of free T4) hypothyroidism, and this has indeed been

Shifts in the occurrence of thyroid disorders with a change in the iodine intake of the population

It is well documented that programmes directed to increase the iodine intake of iodine-deficient populations will eradicate endemic cretinism and endemic goitre.66 This is the background for international recommendations on iodine intake and for the many national iodine fortification programmes.

However, the international recommendation is also against an excessive increase in iodine intake of a population, and this should be monitored.66 This recommendation is based on the finding that an

Iodine memory?

One pertinent question when evaluating the association between current iodine intake and the epidemiology of disease in a population is to what degree a previous exposure to a different level of iodine intake (low or high) may have influenced the current occurrences of diseases. For example, brain damage caused by iodine deficiency in early life is not reversible, even if the iodine intake becomes normal.

An increase from low to normal iodine intake is associated with a reduction in thyroid size

Conclusion

Both low and high levels of iodine intake associate with an increase in the risk of disease in a population. Optimally, iodine intake of a population should be kept within a relatively narrow interval where iodine deficiency disorders are prevented, but not higher.

Practice points

  • The primary priority in iodine nutrition is to avoid severe iodine deficiency with insufficient thyroid hormone production and to prevent developmental brain damage.

  • Developmental risk is also present in moderate iodine

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