**5. Maternal-fetal thyroid in hyperthyroid state (Figure 3)**

Neonatal hyperthyroidism was described as a critical disease marked mainly by cardiac symptoms, poor weight gain and severe neurological manifestations [1,133-137]. Fetal thyrotoxicosis is the result of thyroid-stimulating antibody transfer to the fetus in the setting of maternal Grave's disease [2,138]. It may present with a variety of clinical features, which include persistent sinus tachycardia, fetal hydrops, intrauterine growth restriction, goiter and fetal demise [1,139]. The vast majority of cases of excessive serum TH concentration seen in pregnancy are due to the overproduction of THs (Graves' disease, toxic nodular goiter); in the postpartum period, thyrotoxicosis may be due to exacerbation of Graves' hyperthyroidism or to the release of thyroid hormone due to an acute autoimmune injury to the thyroid tissue (postpartum thyroiditis-PPT) [2,140].

The management of hyperthyroidism in pregnancy, which most often is caused by Graves' disease, has been reviewed recently [141,142]. Hyperthyroidism occurs in about 0.2–0.4% of all pregnancies. Hyperthyroidism should be distinguished from gestational transient thyrotoxicosis, which is due to the TSH-receptor stimulating effects of hCG [143,144]. This hCGinduced hyperthyroidism is mostly mild and need not be treated. Only rare cases with extremely high hCG (i.e. due to a hydatidiform mole) might induce severe thyrotoxicosis [145]. The signs and symptoms of hyperthyroidism due to Graves' disease may aggravate in the first trimester and thereafter may become mild. Untreated hyperthyroidism is associated with severe

effects on maternal and neonatal outcome. The risk for premature fetal loss, preeclampsia, preterm delivery, intrauterine growth retardation and low birth weight is significantly increased [144]. It has to be considered that the transfer of stimulating receptor antibodies (TSAbs) are transferred from the mother to the child, and therefore the fetus is at risk to develop Graves' disease. Close monitoring of the fetus is, therefore, strictly recommended, even in mothers treated by thyroidectomy before pregnancy but have still elevated TSAbs [142].

Maternal-Fetal Thyroid Interactions 139


during neurulation.

24 h - mRNA levels of DI, DII and DIII are detected in whole

embryos.

48 h - OATP1c1 expression appears.

about the developmental thyroid hormone mechanisms (deiodinases, transporters, sulfotransferases and receptors) in human [1,2,50,52,127,130,151-154], rat [1,2,41,60,135,154- 156] and chicken [7,157-170]. Note that the chicken is born early compared to the rat and

Human Rodent (rat) Chicken Week post conception Day post conception Incubation day

> 5 h (blastula stage)

1 GD DII and DIII are observed in uterine wall.

> - Time of implantation process.

9 GD - Thyroid gland

cavity.

in rat

asts


is first visible as an endodermal thickening in the primitive buccal


embryotrophobl

human, as well as the rat is born early compared to the human (Table 6).

7 -8.5 GD

**6. Summary** 

1 W - DIII is detected in uterine wall.

3 W - Thyroid gland begins.

4-6 W - TBG is observed in thyroid follicle cells at GD 29. - TRH is detected in fetal wholebrain at 4.5 weeks of gestation. - T4 is transferred *via* the placenta and has been found in the gestational fluid sac from 4 to 6 W.

> - Maternal-embryo transfer of THs has been detected in embryonic coelomic fluid and amniotic fluid. - All the mRNAs encoding THTs are expressed in placenta from 6 W and throughout pregnancy.

5-11 W

**Figure 3.** Different cases of hyperthyroidism.

Taken together, there are two known causes of central hyperthyroidism [1,146]; (1) TSHproducing pituitary tumors (TSHomas) and (2) the syndrome of pituitary resistance to thyroid hormone (PRTH). In general, thyrotoxicosis is the syndrome resulting from an excess of circulating free T4 and/or free T3 [147,148]. Babies likely to become hyperthyroid have the highest TSH receptor antibody titer whereas if TSH receptor antibodies are not detectable, the baby is most unlikely to become hyperthyroid (Figure 3) [1,2,149]. In the latter case, it can be anticipated that the baby will be euthyroid, have transient hypothalamic-pituitary suppression or have a transiently elevated TSH, depending on the relative contribution of maternal hyperthyroidism versus the effects of maternal antithyroid medication, respectively [150].
