Selenium iodine deficiency

Nonmetallic elements predominating in the ash are phosphorus (700 g in the human body), sulfur (175 g), and chlorine (105 g). Not only are these three elements essential to all living cells but also selenium, fluorine, silicon (Box 4-B), iodine, and boron are needed by higher animals and boron by plants (Fig. 1-17). Iodine deficiency may affect one billion human beings and may cause 20 million cases per year of cretinism, or less severe brain damage.158... 

One report suggests that therapeutic use of selenium in the form of selenite could precipitate hypothyroidism, but the circumstances were complex and iodine deficiency seems to have played a major role (1061). 

Synergistic interactions occur in other tissues and can have important biological and clinical consequences. For example, die interaction between selenium and iodine has been investigated.It is known that deiodinases are selenoproteins and that they remove iodine from T4 to produce the biologically active T3. Also the selenoprotein glutathione peroxidase is active in the thyroid in the destruction of excess hydrogen peroxide and is therefore important in thyroid hormone production. In certain areas of the world, combined selenium and iodine deficiency can occur and affect treatment provision of selenium maybe necessary to correct hypothyroidism, but also may precipitate its onset. 

Endocrine Effects. Thyroid hormone metabolism is the result of a balance in iodine and selenium levels. Selenium is a component of the deiodinase enzymes, including the Type I and Type II iodothyronine 5 -deiodinases, which convert the prohormone thyroxine (T4) to the active form, triiodothyronine (T3) (Kohrle 1994 St Germain and Galton 1997). Iodine deficiency can lead to hypothyroidism but if iodine deficiency is accompanied by selenium deficiency, thyroid gland destruction may also occur (Contempre et al. 1991a Hofbauer et al. 1997). Supplementation of individuals deficient in both iodine and selenium with selenium produces a further decrease in thyroid function, but if selenium supplementation is preceded by normalization of iodine levels, normal thyroid function is restored (Contempre et al. 1991a, 1992). 

Intermediate-Duration Exposure. No human studies of intermediate inhalation exposure to selenium were located. Following oral exposure, one study in humans revealed endocrine effects in iodine-deficient individuals (Contempre et al. 1991a, 1992) and others revealed endocrine effects in individuals receiving sufficient levels of iodine (Duffield et al. 1999 Hawkes and Keim 1995). Results from one study in humans revealed dermal effects following intermediate dermal exposure (Pringle... 

Contempre B, Dumont JE, Ngo B, et al. 1991a. Effect of selenium supplementation in hypothyroid subjects of an iodine and selenium deficient area The possible danger of indiscriminate supplementation of iodine-deficient subjects with selenium. J Clin Endocrinol Metab 73(1) 213-215. 

The interrelationship among iodine deficiency, selenium deficiency and the activity of thyroid hormones (thyroxine 5 -deiodi-nase-1) was identified in the early 1990 s, when iodine and selenium were found to be necessary for reducing T4 in the cell-active T3 in animals and man (Behne et al. 1988, 1990, Arthur etal. 1990, Arthur 1992, Beckett et al. 1987, 1993, Berry et al. 1991, Larsen and Berry 1995). 

The pituitary and brain, as well as brown adipose tissue, contain DI2 and DI3, which catalyze 5 - and 5-deiodination, respectively. Selenium deficiency alone has no effect on thyroid weight in rats, whereas iodine deficiency results in a 60% increase, and concurrent iodine and selenium deficiency results in a thyroid weight 148% above that of control animals. The principal physiological role of DI2 is the local intracellular production of T3. The role of DI3 has been proposed to protect fetal tissue from high levels of T3 and T4 during development by converting them to r T3 and r T4, respectively (Sunde 1997) (r = reverse). 

Figure 51.1 Antioxidant enzyme activities and LP levels in thyroid tissues of iodine- and selenium-deficient rats. Source Giray ef a/., 2004, with kind permission from Wiley-Liss. Superscripts of different letters differ significantly Ip < 0.05) from each other. Abbreviations C, control group ID, iodine-deficient group SeD, selenium-deficient group cGPx, glutathione peroxidase SOD, superoxide dismutase CAT, catalase TEARS, thiobarbituric acid reactive substances LP, lipid peroxidation.

When there is selenium deficiency coupled with iodine deficiency, through an increased availability of H2O2 and a decrease in thyroid GPx activity, the stimulated thyroid gland is possibly exposed to greater levels of H2O2, and in turn, to highly reactive peroxides. 

The clinical relevance of selenium deficiency is more difficult to estabhsh than that of iodine deficiency. Moderate selenium deficiency is present in some regions of Europe, but it has not been associated with any cfinical condition in humans. Nonetheless, the degree of selenium deficiency in Finland was considered severe enough to implement a control program based on the supplementation of fertilizers with selenium (Aro et ai, 1995). New Zealand adopted the same strategy, because of the beneficial effects of selenium supplementation on the productivity of their animal industry. 

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. 

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. 

In Tibet, both endemic goiter and KBD are important public health problems. KBD occurs in areas of Tibet where selenium deficiency is endemic. In Tibet, as in most regions of China where selenium deficiency is endemic, iodine deficiency is also endemic, but the converse is not... 

A twelve-month selenium-supplementation trial in children with KBD in Tibet did not show any effect on the main symptoms and signs of the disease (Moreno-Reyes et al., 2003). But, in the same study, correction of iodine deficiency before the administration of selenium supplements induced partial recovery of growth retardation. Selenium had no additional effect on either growth or thyroid function, despite the normalization of serum-selenium levels. 

In KBD subjects, the evolution of thyroid function after correction of iodine was similar in selenium supplemented and nonsupplemented subjects. This finding corroborated previous studies, suggesting only a moderate effect of selenium deficiency on thyroid hormones in human (Calomme et al, 1995 St. Germain and Galton, 1997). In Tibet, the administration of an intramuscular injection of 475-mg of iodine to KBD subjects was sufficient to correct iodine deficiency for 16 months, because at this time serum T3 increased again to pre-iodine levels and mean iodine urinary concentrations had fallen... 

Altogether this data suggest that the effect of selenium supplementation on growth and thyroid function in selenium- and iodine-deficient subjects is not significant once iodine deficiency is corrected (Figures 71.11 and 71.12). 

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