Francisco Escobar del Rey

Iodine Deficiency, Implications for Mental and Psychomotor Development in Children1

Endemic goiter and endemic cretinism are an important national health problem in various countries. Although several ecological factors may contribute to the development of endemic goiter (1–3), iodine deficiency is assumed to be the major one (4). This assumption is supported by the positive effects of prophylactic measures- especially the administration of iodinated salt and iodized oil — on the mental and physical development of people from severely iodine-deficient areas. For its hormone production, the thyroid gland requires a certain amount of iodine, which is taken in the form of iodinated salts present in food and drinking water. Severe and prolonged iodine deficiency frequently leads to an enlargement of the thyroid gland (goiter), the volume of which may vary strongly. Such an enlargement is found more often in females than in males (5–9). Goiter is usually defined in the terms proposed by Perez et al. (10), a definition later adopted by the World Health Organization in a slightly different wording: “a thyroid gland whose lateral lobes have a volume greater than the terminal phalanges of the thumbs of the person being examined will be considered goitrous”. The volume of the enlargement is usually defined according to a four-graded division, ranging from OB (detectable only by palpation and not visible even when the neck is fully extended) to III (visible from a long distance).

Models of Fetal Iodine Deficiency

An experimental model would obviously be of great importance to define the etiopathological factors leading to the neurological damage of the cretins, and to poor mental and psychomotor development of inhabitants of iodine-deficient areas. We shall only describe the rat model, as other animal models are being dealt with by Dr. Basil H. Hetzel.

Regulation of Intracellular Thyroid Hormone Concentrations in the Fetus

Thyroid hormones play an important role in development1, especially in brain development2, 3. The role of thyroid hormones in development include the stimulation of skeletal maturation, the diferentiation of central nervous system, and they seem to regulate other processes such as the maturation of lung and the process of non-shivering thermogenesis in the neonate. Most of the information available is based on experimental models, mainly in the rat and sheep, due to the obvious difficulties to examine the effects of thyroid hormone deficiency in the human developing brain.

Field and Experimental Studies of Iodine Deficiency in Spain

Complete bibliographic references may be found elsewhere1. References to only a few studies are given here.

Adaptation to Iodine Deficiency: Experimental Aspects: T4 and T3 in Plasma and Different Tissues

Publisher Summary This chapter stresses the importance of TSH-independent autoregulatory responses that are rapidly activated by mild ID, including an increase in thyroid weight and activation of the preferential synthesis of T3 over T4, resulting in the maintenance of elevated, or normal, circulating T3, even in severe ID. Very severe ID is needed to decrease the circulating T3 below normal values. Experimental models of ID have afforded important relevant information for man. Any degree of ID, even if mild, ought to be avoided because it rapidly activates TSH-independent autoregulatory mechanisms that result in goiter, and an increased incidence of thyroid disorders accompanying thyroid hyperplasia. A combination of intra- and extrathyroidal mechanisms of adaptation leads to the preferential synthesis and secretion of T3 over T4, as a consequence of which circulating T3 levels are normal, or even increased, at the expense of decreasing circulating T4 concentrations. Circulating T3 only decreases in situations of very severe ID. Extrathyroidal consequences of the changes in circulating T4 and T3 are not the same for all tissues. At all degrees of ID, indices of thyroid hormone status are clearly tissue specific: elevated, normal, and low concentrations of T3 are found in different tissues of the same animal. circulating T3 has to decrease before many T3-dependent tissues become hypothyroid. This appears to occur when circulating T4 decreases from 25% to 5% of normal values. But even under such conditions, the many known and as yet undefined intra- and extrathyroidal adaptive mechanisms are efficient enough to maintain euthyroidism in muscle and heart, and even slightly elevated T3 in lung and ovary.This chapter stresses the importance of TSH-independent autoregulatory responses that are rapidly activated by mild ID, including an increase in thyroid weight and activation of the preferential synthesis of T3 over T4, resulting in the maintenance of elevated, or normal, circulating T3, even in severe ID. Very severe ID is needed to decrease the circulating T3 below normal values. Experimental models of ID have afforded important relevant information for man. Any degree of ID, even if mild, ought to be avoided because it rapidly activates TSH-independent autoregulatory mechanisms that result in goiter, and an increased incidence of thyroid disorders accompanying thyroid hyperplasia. A combination of intra- and extrathyroidal mechanisms of adaptation leads to the preferential synthesis and secretion of T3 over T4, as a consequence of which circulating T3 levels are normal, or even increased, at the expense of decreasing circulating T4 concentrations. Circulating T3 only decreases in situations of very severe ID. Extrathyroidal consequences of the changes in circulating T4 and T3 are not the same for all tissues. At all degrees of ID, indices of thyroid hormone status are clearly tissue specific: elevated, normal, and low concentrations of T3 are found in different tissues of the same animal. circulating T3 has to decrease before many T3-dependent tissues become hypothyroid. This appears to occur when circulating T4 decreases from 25% to 5% of normal values. But even under such conditions, the many known and as yet undefined intra- and extrathyroidal adaptive mechanisms are efficient enough to maintain euthyroidism in muscle and heart, and even slightly elevated T3 in lung and ovary.

Experimental Models of Iodine Deficiency and Cretinism during Development

Neurological cretinism is caused by severe iodine deficiency during pregnancy, and is characterized by severe mental retardation, neurological and motor abnormalities. It can be corrected by administration of iodine before conception. The clinical features of cretinism are different from the clinical signs of hypothyroidism found in congenital hypothyroidism. In iodine deficiency the maternal plasma T4 is usually low, even with normal plasma T3 and slightly elevated or normal TSH. The cause of the neurological abnormalities is thought to be the lack of thyroid hormones during the first period of brain development, and specifically maternal hypothyroxinemia early in pregnancy. Maternal transfer of T4 during gestation has a protective role during the development of the fetal brain, as most of the T3 in the fetal brain is locally produced from T4 by D2 deiodinase. Development of the neocortex can be affected by short periods of maternal hypothyroxinemia, before the onset of fetal thyroid function. Therefore, to maintain normal thyroxinemia in the mother is of maximal importance to maintain normal T3 levels in the fetal brain.

Experimental Models of Iodine Deficiency and Cretinism during Development: The Role of the Mother

Neurological cretinism is caused by severe iodine deficiency during pregnancy, and is characterized by severe mental retardation, neurological and motor abnormalities. It can be corrected by administration of iodine before conception. The clinical features of cretinism are different from the clinical signs of hypothyroidism found in congenital hypothyroidism. In iodine deficiency the maternal plasma T4 is usually low, even with normal plasma T3 and slightly elevated or normal TSH. The cause of the neurological abnormalities is thought to be the lack of thyroid hormones during the first period of brain development, and specifically maternal hypothyroxinemia early in pregnancy. Maternal transfer of T4 during gestation has a protective role during the development of the fetal brain, as most of the T3 in the fetal brain is locally produced from T4 by D2 deiodinase. Development of the neocortex can be affected by short periods of maternal hypothyroxinemia, before the onset of fetal thyroid function. Therefore, to maintain normal thyroxinemia in the mother is of maximal importance to maintain normal T3 levels in the fetal brain.

Iodine Deficiency in Spain: Update of A Widespread and Persisitng Problem

Studies on endemic goiter, cretinism and iodine deficiency in Spain up to the mid-eighties were summarized in a monographic issue1 of the Spanish journal Endocrinologia, the official publication of the Spanish Society of Endocrinology, English summaries of the different articles having appeared in an IDD Newsletters2. This issue included a chapter on 100 years of literature about endemic goiter in Spain, 173 reports between 1885 and 1985, which showed that the existance of the problem was widely recognized, mostly as result of interested doctors and scientists, but it persisted due to lack of sustained interest to eradicate it on behalf of the health authorities and the different Central Administrations with the executive power to eradicate it. These studies showed that in the seventies and early eighties goiter endemias were frequent in Andalusia (VII-1, see the map of Spain, Figure 1), Cataluna (III), Asturias (XIV), Guadalajara (VIII-1), Galicia (XV) and Extremadura (VII). Most studies included determinations of urinary iodine. The endemias ranged from grade I severity to grade III in some parts of Extremadura (Las Hurdes, VII-1) and of Galicia (XV-1, XV-2). The studies in Las Hurdes have been described in detail, including a psychometric evaluation showing that mental development of the iodine-deficient schoolchildren was negatively affected3,4.