Myxedematous cretinism, iodine

Selenium deficiency has been associated with specific diseases in China and Africa Keshan and Kashin-Beck disease (KBD) in Tibet and China and myxedematous cretinism in Central Africa. Interestingly, in all these selenium-deficient areas iodine deficiency is also endemic. The specific impact of iodine deficiency on human health is described elsewhere in this book and will not be repeated here, with the exception of health conditions where the interaction of iodine and selenium may contribute to the pathogenesis of a specific disease. This chapter will deal with diseases where both iodine and selenium deficiency play a role in disease causation and particularly with KBD. 

Goyens et al (1987) hypothesized that the thyroid atrophy of myxedematous cretins could result from the toxic effect of increased H2O2 generation by the thyro-cytes due to chronic TSH stimulation induced by iodine deficiency. The decreased activity of enzymes, such as GSH peroxidase, which normally protect thyrocytes and... 

Urinary iodine concentrations in Tibet are very similar to those observed in Sudan (Moreno-Reyes et ai, 1993), but the frequency of goiter or hypothyroidism is lower. The lack of goitrogens in Tibet probably explains the lower frequency of hypothyroidism and goiter despite similar urinary iodine concentrations to those in Central Africa. Experimentally, the involvement of thiocyanate in the pathogenesis of myxedematous cretinism has recently been corroborated (Contempre et al, 2004). 

Myxedematous cretinism would result from fetal hypothyroidism later in pregnancy - a condition that can be reversed with treatment by thyroid hormones or correction of the iodine deficiency - but the earlier damage in mid-trimester appears to be irreversible. 

We know that endemic cretinism can be prevented by the normalization of iodine intake in the population, for example by the introduction of iodized salt. It can also be prevented by giving injections of iodized oil to mothers during early or even late pregnancy in the case of myxedematous cretinism (Reviews in 3-6). We also know that newborns are more sensitive than children and adults to the antithyroid effects of both iodine deficiency and iodine excess (84). 

Endemic cretinism has been a common finding in the mountains or isolated regions, such as the Alps or the Himalayas and has been described or depicted in drawings over the centuries. McCarrison (1917) studied this condition in the Himalayas, describing two types of cretinism the nervous and myxedematous types. He already suspected the influence of the maternal thyroid function on the fetus. Early observations in the Alps (Hunziker-Shild, 1915) already reported that the fetus could receive the hormone from the mother, and proposed the prophylactic administration of iodine from conception. 

However, some observations from other goiter endemic areas did not support the selenium-iodine hypothesis. First, selenium deficiency in Central Africa is not as severe as in the selenium- and iodine-deficient areas of Tibet, where the neurological and not the myxedematous type of cretinism is most frequent (Moreno-Reyes et al, 1998) Figure 71.4. 

Finally, iodine deficiency during gestation in animals results in thyroid deficiency in the offspring. All the models used mimic the myxedematous type of cretinism none was able to produce the neurological type (16). 

Another major effect of fetal iodine deficiency is the condition of endemic cretinism. This condition, which occurs with an iodine intake of below 25 ug per day in contrast to a normal intake of 100-150 ug per day, is still widely prevalent, affecting for example up to 10 per cent of the populations living in severely iodine deficient areas in India, Indonesia and China. In its most common form, it is characterised by mental deficiency, deaf mutism and spastic diplegia, which is referred to as the "nervous" or neurological type in contrast to the less common "myxedematous" type characterised by hypothyroidism with dwarfism. 

---