Over a period of almost 10 yr, we carried out a prospective study of the neuropsychological development of the offspring of 16 women from a moderately iodine-deficient area (area A) and of 11 control women from a marginally iodine-sufficient area (area B) whose thyroid function had been monitored during early gestation. Attention deficit and hyperactivity disorder (ADHD) was diagnosed in 11 of 16 area A children (68.7%) but in none from area B. Total intelligence quotient score was lower in area A than in area B children (92.1 +/- 7.8 vs. 110 +/- 10) and in ADHD children when compared with both non-ADHD children from the same area and control children (88.0 +/- 6.9 vs. 99.0 +/- 2.0 and 110 +/- 10, respectively). Seven of 11 ADHD children (63.6%) were born to the seven of eight area A mothers who became hypothyroxinemic at early gestation, whereas only one of five non-ADHD children was born to a woman who was hypothyroxinemic at 20 wk of gestation. So far, a similar prevalence of ADHD has been reported only in children with generalized resistance to thyroid hormones. This might suggest a common ADHD pathogenetic mechanism consisting either of reduced sensitivity of the nuclear receptors to thyroid hormone (generalized resistance to thyroid hormones) or reduced availability of intracellular T3 for nuclear receptor binding. The latter would be the ultimate consequence of maternal hypothyroxinemia (due to iodine deficiency), resulting in a critical reduction of the source of the intracellular T3 available to the developing fetal brain.

Prolonged iodized salt significantly improves maternal thyroid economy and reduces the risk of maternal thyroid insufficiency during gestation, probably because of a nearly restoring intrathyroidal iodine stores.

Objective: To longitudinally evaluate the timing of maternal thyroid underfunction occurrence in mildly iodine-deficient (ID) pregnant women, and ultimately assess the benefit of thyroid function testing at early gestation only in identifying maternal thyroid underfunction. Participants/methods: Serum free-thyroxine and TSH were measured in 220 consecutive women once in early pregnancy (by week 12) and twice per trimester subsequently. Anti-thyroperoxidase and antithyroglobulin were also determined at initial and final observation. Results: Thyroid autoantibodies were detectable in 8.2% women. Overall, the prevalence of hypothyroidism over the course of gestation was 11.8% (26/220), with a relative risk of hypothyroidism in antibody-positive women of 5.0 (c 2 20.02, P!0.0005). Nonetheless, almost 70% hypothyroid women tested negative for thyroid autoantibodies. Fifteen/26 (57.7%) hypothyroid women were identified at presentation, and the remaining 11 at either early (6/11) or late (5/11) phases of the 2nd trimester. Isolated hypothyroxinemia was observed in 56/220 (25.4%) women, mostly from the 2nd trimester onwards. Conclusions: In mildly ID areas thyroid function testing early in gestation seems to be only partly effective in identifying thyroid underfunction in pregnant women. Indeed, in our series more than 40% hypothyroid women would not have been diagnosed had we limited our observation to early thyroid function tests alone. Although thyroid autoimmunity carried a 5-fold increased risk of hypothyroidism, iodine deficiency seems to be a major determinant in the occurrence of thyroid underfunction. Adequate iodine supplementation should be strongly recommended to meet the increased hormone demand over gestation.

Circulating thyroglobulin antibodies (TgAb) and thyroperoxidase antibodies (TPOAb) were measured in 143 iodine-deficient children, 5 to 15 years of age, from the Region of Tula, Russia, who had been moderately contaminated after the Chernobyl disaster (37-185 GBq/km2 of caesium-137, [group A]) and in 40 sex- and age-matched subjects from an uncontaminated neighboring area (<3.7 GBq/km2 of caesium-137, [group B]). Increased thyroid size at sonography was found in 41% and in 45% subjects from group A and group B, respectively, associated with supranormal thyrotropin (TSH) values in 7.7% of group A and 7.5% of group B, without differences in average serum free thyroxine (FT4), free triiodothyronine (FT3) and TSH. Serum thyroperoxidase antibody (TPOAb)-associated or not with thyroglobulin-antibody (TgAb) as detected in 18.9% of children and adolescents from group A, about four-fold higher than in group B (5%, Fischer's exact test p<0.05). A 24% frequency was found in subjects whose age, at the moment of the disaster was 0-72 months or were in utero, but the frequency was about 7%, similar to that in group B, in those who had not yet been conceived at that time. Less than half of antibody-positive group A children were hyperthyrotropinemic, whereas no group B subclinical hypothyroid subject was antibody-positive, thus excluding the autoimmune etiology of the subclinical thyroid failure; more likely it is attributable to iodine malnutrition. The high prevalence of humoral thyroid autoimmunity phenomena in the investigated area suggests a combined role of iodine malnutrition in enhancing the effects of short lived iodine isotopes, particularly evident in pubertal individuals conceived or born immediately before the Chernobyl disaster.

In an effort to assess the impact of moderate iodine deficiency on maternal thyroid function during pregnancy, we measured serum thyrotropin, total and free thyroid hormones, thyroid-binding globulin (TGB) at 8, 14, 20, 29, and 36 weeks of gestation, along with urinary iodide excretion, in 10 healthy women from a moderately iodine deficient region (group A), and compared them with 6 women from an iodine sufficient region (group B). Serum total thyroxine (T4) fell significantly in group A, and was significantly lower than in group B at 29 and 36 weeks (p<0.05). TBG saturation was significantly lower in group A throughout pregnancy, and declined in both groups as pregnancy progressed. Free thyroxine (T4) and triiodothyronine (T3) concentrations fell in both groups, and FT4 values were significantly lower in group A than group B in the third trimester (p<0.05). Urinary iodine excretion was lower in group A women with respect to group B and did not vary significantly in either group as gestation progressed. The serum T3/T4 molar ratio increased through pregnancy only in group B. Thyrotropin concentrations rose in both groups through pregnancy, and were higher in group A at term (p< 0.01). The incidence of isolated hypothyroxinemia or biochemical hypothyroidism doubled (30% to 70%) between midgestation and term in group A, suggesting that moderate iodine deficiency may result in maternal thyroid failure during the later stages of pregnancy.