Thyroid hormones recent developments

There are many reviews available on the biochemistry of thyroid hormones27-30 including the excellent review by Doonan in this Series1. Biosynthesis and metabolism of thyroid hormones will be reviewed briefly in this chapter. Attention will be given to recent developments relating to the mechanisms responsible for the physiological responses to thyroid hormones. 

The importance of the transfer of thyroid hormones from the mother to the fetus during the second half of pregnancy in humans has received increasing attention (Burrow et ai, 1994). Recently, it has become evident that maternal hypothyroxinemia results not only in the birth of children with neurological cretinism, but also in decreased mental and psychomotor development of the rest of the population without cretinism (Beichrodt and Born, 1994). 

The two most recent NHANES surveys showed that for women of childbearing age and pregnant women, the median UI excretion levels were adequate (127 and I4lpg/1, respectively, in 1988-1994 132 and 173 pg/1, respectively, in 2001-2002) (Table 115.3) (Caldwell et al., 2005). Thyroid hormone, requiring adequate iodine intake, is critical for neural development in utero and in early life. Although cretinism due to iodine deficiency is not a problem in the United States, subtle developmental delays could result from mild maternal iodine deficiency. 

It is not the purpose of this section to review the intricacies of the metabolic effects of the thyroid hormones, but rather to compare the relative contributions made by T3 and Ti, respectively, to overall metabolism. It is only in recent years that the degree of the contribution made by Ts has been realized, and this has far-reaching consequences not only in regard to the physiology of the thyroid secretion, but also in respect to the recent development and application of thyroid function tests. In addition there are significant pathophysiologic and therapeutic implications. 

The purpose of this section is to summarize those procedures carried out on patients which depend upon certain physiological aspects of thyroid function including the interrelationship of the thyroid gland with the hypothalamus and the anterior pituitary glands. The TSH stimulation and the Ts suppression tests are only briefly discussed, mainly for historical reasons, as both are becoming redundant because of more recent developments such as TSH and T3 assays, and the diagnostic use of thyrotropin releasing hormone. 

The mechanism of action of thyroid hormone upon lipid and lipoprotein metabolism is not established. Olson and Vester (1960) have reviewed the literature on the subject. Only recent developments will... 

Of the hyperlipidemic drugs, clofibrate appears to decrease fecal elimination of bile acids (278-280). However, this decrease is less than the increase of the neutral steroid output, so the net elimination of cholesterol is increased (280). Thyroid hormones may occasionally, especially if associated with diarrhea, cause a marked increase in bile acid elimination (see Section VIIB), while nicotinic acid only occasionally augments fecal bile salt output (221, 281). Of the more recently developed absorbable hypolipidemic drugs, DH-581 appears to stimulate bile acid excretion at least transiently, probably by inhibiting intestinal bile acid reabsorption (282). 

These observations suggested that normal brain development requires the availability of both maternal and fetal thyroid hormones,a suggestion which is at variance with earlier reports (9) (14) (15) (16) that the placenta in many mammalian species is relatively impermeable to thyroid hormones and with the suggestion (17) (18) that early mammalian development takes place normally in the absence of thyroid homrones. The observations do agree however with a more recent report (19) that rat embryonic tissues are provided with T and T3 only four days after uterine implantation and well before the onset of fetal thyroid function at 17 days. y also supported by the work of Woods et al (20) who showed that T and T3, when injected into pregnant rats, entered the rat... 

Bonet and Herrera and Esa ar et al have recently reported that thyroid hormones cross the placenta from dam to fetus and that maternal hypothyroidism does affect fetal growth and development and brain T3 cc itent. Further studies in the rat and other species, inclxiding man, will further clarify this question. 

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