Thyroxine maternal

Hypothyroid women frequently have anovulatory cycles and are therefore relatively infertile until restoration of the euthyroid state. This has led to the widespread use of thyroid hormone for infertility, although there is no evidence for its usefulness in infertile euthyroid patients. In a pregnant hypothyroid patient receiving thyroxine, it is extremely important that the daily dose of thyroxine be adequate because early development of the fetal brain depends on maternal thyroxine. In many hypothyroid patients, an increase in the thyroxine dose (about 30-50%) is required to normalize the serum TSH level during pregnancy. Because of the elevated maternal TBG levels and, therefore, elevated total T4 levels, adequate maternal thyroxine dosages warrant maintenance of TSH between 0.5 and 3.0 mll/L and the total T4 at or above the upper range of normal. 

Adequate maternal thyroxine concentration is essential for fetal nervous system maturation. 

In Papua New Guinea, Pharoah and Connolly (1987) have described varying scenarios ranging from stillbirths to cretinism, and less severe neurological defects of motor and cognitive performance. These effects could be correlated with the level of maternal thyroxine (T4), but not with maternal triiodothyronine (T3), indicating the importance of maternal T4 to the fetus. 

Figure 63.1 The figure shows fetal thyroxinemia and the development of thyroxine-dependent organs. Maternal thyroxine Is essential for the neurological development of the fetus.

Most studies show that iodine deficiency and maternal—fetal hypothyroxinemia have negative effects on fetal neural maturation, dendritic arborization and synaptic formation. It also significantly delays axonal myelinization and gfio-genesis, which starts at the third trimester and accelerates in the postnatal period. Recent studies have clearly demonstrated the necessary role of maternal thyroxine in early neurogenesis (de Escobar et al., 2004 Bernal, 2005). 

Adequate maternal thyroxine transfer to the fetus during early gestation is crucial, as the maternal thyroid is the only source of T4. The extent of neurological damage in progeny can... 

This is further indicated by evidence of the relation of maternal thyroxine levels to the risk of cretinism and the psychomotor defect from studies in Papua New Guinea (26). The subsequent lack of fetal thyroid hormones due to the inadequate supply of iodine in iodine deficiency would exacerbate the effects of maternal thyroid insufficiency and the combination of effects, which were represented experimentally in the sheep by maternal thyroidectomy before conception (21) combined with fetal thyroidectomy at 98 days (12), might be expected to produce the multiple defects of neurological cretinism. 

IODINE DEHOENCY, MATERNAL THYROXINE LEVELS IN PREGNANCY AND DEVELOPMENTAL DISORDERS IN THE CHILDREN... 

Another case (serial no 398) is of particular interest in that the child exhibits the clinical features of cretinism The maternal thyroxine and TSH values were abnormal and consistent with hypothyroidism but the triiodothyronine values were within the normal... 

There is a spectrum of Impairment ranging from death through clinical endemic cretinism and subclinical deficits of motor and cognitive performance, to normality. This spectrum of effects appears to be associated with maternal thyroxine during pregnancy. No association with maternal triiodothyronine was found. 

Neurological effects associated with phthalate exposure also have been reported in human studies. Although a mechanism of action has not been demonstrated, it is hypothesized that disruption of maternal thyroxine levels may contribute to the downstream clinical effects of thyroid dysfunction (Meeker et al. 2007). 

Further data from Papua New Guinea indicates a relationship between the level of maternal thyroxine with the outcome of current and recent past pregnancies including mortality and the occurrence of cretinism. There were proportionally more perinatal (i.e., stillbirths and neonatal) deaths, and cretins, among the offspring of women who showed the lowest levels of serum thyroxine ... 

These data, indicating the importance of maternal thyroid function to fetal survival and development, are complemented by extensive animal data. Recent findings from the study of experimental animal models and more recently in man, indicate that there is a transfer of maternal thyroxine early in pregnancy. It would seem likely therefore that the effects of iodine deficiency on the fetus are... 

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