Fetal thyroidectomy

To investigate these various possibilities an animal model was developed in the sheep (Figure 62.4), because of the access provided for both maternal and fetal thyroidectomy and previous experience with trace element deficiencies (Hetzel, 1976). Subsequently, a similar model was developed in the primate marmoset monkey Callithrix jacchus jacchus) (Mano et ai, 1987) and in the rat (Li et al., 1985 Morreale de Escobar et ai, 1993). 

The effects of severe iodine deficiency on fetal brain and somatic development were found to be more severe but similar to those observed by McIntosh et al (10) when thyroidectomy was performed on fetal sheep at 50-60 days. Fetal thyroidectomy later in gestation at 98 days caused less severe effects (11). Further investigations by McIntosh et al (12), following earlier indications (13) that the maternal thyroid could exert an influence on fetal development in early pregnancy, revealed that a combination of maternal thyroidectomy before conception and fetal thyroidectomy at 98 days gestation produced more severe effects than those of iodine deficiency (Fig. 1). 

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. 

Studies of the mechanisms involved have been carried out in the sheep. The findings reveal significant, though less severe, effects of fetal thyroidectomy (late gestation) and a significant effect of maternal thyroidectomy on brain development in mid gestation. A combination of maternal and fetal thyroidectomy has similar but more severe effects than iodine deficiency. 

The effects of 98 day fetal thyroidectomy on brain development in the sheep. J. Comp. Path. 92 599-607 (1982). 

Hetzel, B.S. The effect of maternal and fetal thyroidectomy on fetal brain development in the sheep. Neuropath. Appl. Neurobiol. 9 215-223 (1983). 

Potter et al (21) extended and confirmed their earlier observations and were able to show that surgical thyroidectomy of ewes 6 weeks prior to conception caused a reduction in fetal brain and body growth in mid-gestation compared to that of fetuses from sham-operated ewes. The differences were no longer evident in the neonatal brain at parturition after the onset of fetal thyroid function but the possibility of residual damage remains to be explored with behavioural and functional studies of brain function. 

The number of fetuses per litter in the LID dams (8.8 0.6) was decreased as compared to LID+I mothers (11.2 0.6) and so is their body weight ( 4.19 0.09 versus 4.72 0.10 g). The weight, total DNA and total protein content of the fetal brain were also decreased at 21 dg in LID fetuses. These effects of ID were less marked than those resulting from thyroidectomy of the dams... 

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