Hypothyroidism, riboflavin

The activities of a variety of flavin-dependent enzymes are depressed in hypothyroidism. They are increased by the administration of thyroxine or triiodothyronine, as a result of increased synthesis of riboflavin phosphate and... 

Tissue concentrations of flavin coenzymes in hypothyroid animals may be as low as in those fed a riboflavin-deficient diet, in hypothyroid patients, erythrocyte glutathione reductase (EGR) activity may be as low, and its activation by FAD added in vitro (Section 7.5.2) as high, as in riboflavin-deficient subjects. Tissue concentrations of flavin coenzymes and EGR are normalized by the administration of thyroid hormones, with no increase in riboflavin intake (Cimino et al., 1987). 

The administration of thyroid hormones to hypothyroid animals results in a rapid increase in flavokinase activity as a result of the activation of an inactive precursor protein as flavokinase activity increases, there is a parallel decrease in the tissue content of an apparendy inactive riboflavin binding protein (Lee and McCormick, 1985). 

Riboflavin may also be involved in the metabolism of thyroid hormones. In the presence of oxygen, riboflavin phosphate catalyzes a photolytic deiod-ination of thyroxine. The lower tissue concentration of riboflavin phosphate in hypothyroidism may thus serve to protect such thyroid hormone as is available against catabolism and prolong its action. 

A number of studies have noted that, in areas where malaria is endemic, riboflavin-deficient subjects are relatively resistant and have a lower parasite burden than adequately nourished subjects. Dietary deficiency of riboflavin, hypothyroidism, which induces functional riboflavin deficiency by lowering the synthesis of flavokinase (Section 7.2.4), or the administration of chlor-promazine, which inhibits flavokinase and can cause functional riboflavin deficiency (Section 7.4.4), all inhibit the growth of malarial parasites in experimental animals. However, although parasitemia is less in riboflavin deficiency, the course of the disease may be more severe (Dutta et al., 1985 Dutta, 1991 Akompong et al., 2000a, 2000b Shankar, 2000). 

Cimino JA, Jhangiani S, Schwartz E, and Cooperman JM (1987) Riboflavin metabolism in the hypothyroid human adult. Proceedings of the Society for Experimental Biology and Medicine 184,151-3. 

The biosynthesis of flavocoenzymes is regulated by the supply of riboflavin, competition for ATP and hormonal balances. Increasing riboflavin concentrations in the intestinal lumen decreases the rate of vitamin absorption, while riboflavin deficiency leads to increased absorption efiiciency. The hormones thyroxine and triiodothyronine stimulate FMN and FAD synthesis in mammals by increasing the activity of flavokinase and for this reason hypothyroidism leads to reduced tissue levels of flavins. In the kidney, aldosterone promotes an increase in the activity of fla vokinase and therefore an increase of flavins. 

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