Cretinism, myxedematous

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. 

What is needed now is a comparison of brain pathology in neurological cretinism and cerebral palsy and in myxedematous cretinism and sporadic congenital hypothyroidism there is also a need for study of the brain in endemic mental retardation. 

What we need is more precise information, obtained with modem methods of investigation, on the structure and ultrastructure of the middle and inner ear in neurological and myxedematous cretins. Such findings should then be compared with data concerning sporadic congenital hypothyroidism and congenital infections. There is undoubtedly scope for further work in audiometry and auditory evoked potentials in endemic and sporadic cretinism. 

Swiss authors (2, 17) reported that neurological cretins have hyperplastic, colloid, multinodular goiters similar to those seen in non cretin individuals in the same area. They showed that myxedematous endemic cretins have thyroid atrophy and sclerosis. As a consequence of their thyroid failure, myxedematous cretins also have hyperplastic pituitary glands. 

We need more information on the structure and ultrastructure of the thyroid in the two types of cretinism. We need to know whether there are specific aspects of thyroid morphology in hypothyroid newborns and stillbirths in endemic areas. We also need to know whether there are age-related changes in the thyroid of hypothyroid infants and children. In other words, how valid is the hypothesis that only progressive atrophy of the thyroid will result in permanent hypothyroidism and myxedematous cretinism in some individuals while the development of compensatory thyroid hyperplasia explains the transient character of hypothyroidism in others (5). Finally, is there any morphological evidence of an autoimmune process within the thyroid ... 

The serum concentration of Selenium is lower in inhabitants of the former goitrous area than in those of the non-goitrous area of Idjwi Island in Zaire (45). It has been speculated that Selenium deficiency could cause oxygen derivatives such as H2O2 to be toxic for the thyroid, and could be one of the factors responsible for thyroid damage resulting in myxedematous cretinism. 

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). 

There are two types of cretinism in China. The major type is neurological cretinism which is found in almost all the cretin endemias of China the myxedematous cretin is the minor type which is found in the north-west part of China. The latter are always mixed with the neurological cretin there is no clear cut demarcation between these two types of cretins. One could consider the different kinds of cretin arranged on a spectrum the typical neurological cretin is on one extremity of the spectrum the typical myxedematous is on the other extremity, and most cretins fall between. 

Table 1. Comparison of Vestibular Function Between Neurological 6e Myxedematous Cretins... 

In some very typical myxedematous cretins in Hetan, the neurological signs are very mild, and difficult to detect by ordinary clinical measurements. 

These criteria were summed up from our experiences in the neurological cretin endemias. Because the clinical type of the myxedematous cretin is so different from the neurological cretin, we could presume that the subclinical type of the myxedematous cretin should be different to a similar degree. 

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