Inadequate iodine nutrition of pregnant women from Extremadura (Spain).

Objective: To evaluate the iodine nutrition of the pregnant women of the Spanish Autonomous Community Extremadura. There are approximately 10,000 births per year in Extremadura, which historically contains areas with endemic goiter (Las Hurdes).

Design: Population study in which a representative sample of pregnant women of the general population was analyzed, along with another sample of pregnant women from traditionally goitrogenic areas.

Iodine deficiency and brain development in the first half of pregnancy.

An inadequate supply of iodine during gestation results in damage to the foetal brain that is irreversible by mid-gestation unless timely interventions can correct the accompanying maternal hypothyroxinemia. Even mild to moderate maternal hypothyroxinemia may result in suboptimal neurodevelopment. This review mainly focuses on iodine and thyroid hormone economy up to mid-gestation, a period during which the mother is the only source for the developing brain of the foetus.

Mechanisms of adaptation to iodine deficiency in rats: thyroid status is tissue specific. Its relevance for man.

Many animals, man included, live in areas providing insufficient iodine (I) for optimal health. Degrees of I deficiency (ID) vary from mild-moderate to very severe, with quali- and quantitatively different negative consequences. To understand the mechanisms involved in adaptation to different grades of ID, we fed rats a low-iodine diet, plus additions resulting in a 250-fold range of I daily available to the thyroid, ranging from 5 mug (adequate) down to 0.

The effects of iodine deficiency on thyroid hormone deiodination.

Iodine deficiency induces multiple intrathyroidal autoregulatory changes leading to an increased triiodothyronine (T(3)) production and secretion, at the expense of thyroxine (T(4)). It is characterized by low serum T(4), normal or slightly elevated T(3), and as a consequence of the latter, normal thyrotropin (TSH). Tissues are also hypothyroxinemic, but their T(3) concentrations are mostly normal and ensure clinical euthyroidism, except for those that depend to a high degree on local generation from T(4) by extrathyroidal mechanisms involving the iodothyronine deiodinases isoenzymes.

REVIEW: Treatment of hypothyroidism with combinations of levothyroxine plus liothyronine.

Context: Combined infusion of levothyroxine plus liothyronine, as opposed to levothyroxine alone, is the only way of restoring the concentrations of circulating TSH, T4, and T3 as well as those of both T4 and T3 in all tissues of thyroidectomized rats. Considering the substantial differences in thyroid hormone secretion, transport, and metabolism between rats and humans, whether or not combined levothyroxine plus liothyronine replacement therapy has advantages over treatment with levothyroxine alone in hypothyroid patients is still questioned.

Evidence Acquisition: We conducted a systematic review of all the published controlled studies comparing treatment with levothyroxine alone with combinations of levothyroxine plus liothyronine in hypothyroid patients, identified through the Entrez-PubMed search engine.

Role of thyroid hormone during early brain development.

The present comments are restricted to the role of maternal thyroid hormone on early brain development, and are based mostly on information presently available for the human fetal brain. It emphasizes that maternal hypothyroxinemia - defined as thyroxine (T4) concentrations that are low for the stage of pregnancy - is potentially damaging for neurodevelopment of the fetus throughout pregnancy, but especially so before midgestation, as the mother is then the only source of T4 for the developing brain. Despite a highly efficient uterine-placental 'barrier' to their transfer, very small amounts of T4 and triiodothyronine (T3) of maternal origin are present in the fetal compartment by 4 weeks after conception, with T4 increasing steadily thereafter.

Hypothyroidism alters the development of radial glial cells in the term fetal and postnatal neocortex of the rat.

Alterations of thyroid function during human development are known to produce extensive damage to the central nervous system including severe mental retardation. Using immunohistochemistry to identify the intermediate filament nestin, we have studied the possible influence of fetal and neonatal hypothyroidism on neocortical neuronal migration by arresting the normal development of the radial glial scaffold. By embryonic day 21 (E21), hypothyroid animals had a significant decrease in the number of nestin immunoreactive processes in the presumptive visual cortex.

Maternal thyroid hormones early in pregnancy and fetal brain development.

During the last few decades our understanding of the possible role of thyroid hormones during brain development has increased and contributed to resolve previously discordant hypotheses, although much remains to be clarified. Thyroid hormones of maternal origin are present in the fetal compartment, despite the very efficient uterine-placental 'barrier', necessary to avoid potentially toxic concentrations of free T4 and T3 from reaching fetal tissues before they are required for development. T3 remains low throughout pregnancy, whereas FT4 in fetal fluids increases rapidly to adult levels, and is determined by the maternal availability of T4.

A moderate and transient deficiency of maternal thyroid function at the beginning of fetal neocorticogenesis alters neuronal migration.

Epidemiological studies and case reports show that even a relatively minor degree of maternal hypothyroxinemia during the first half of gestation is potentially dangerous for optimal fetal neurodevelopment. Our experimental approach was designed to result in a mild and transient period of maternal hypothyroxinemia at the beginning of corticogenesis. Normal rat dams received the goitrogen 2-mercapto-1-methyl-imidazole for only 3 d, from embryonic d 12 (E12) to E15.

Early maternal hypothyroxinemia alters histogenesis and cerebral cortex cytoarchitecture of the progeny.

Epidemiological studies from both iodine-sufficient and -deficient human populations strongly suggest that early maternal hypothyroxinemia (i.e., low circulating free thyroxine before onset of fetal thyroid function at midgestation) increases the risk of neurodevelopmental deficits of the fetus, whether or not the mother is clinically hypothyroid.