Experimental cretinism in lambs: an intrauterine model with thyroid evaluation in surviving lambs

The experiments in this article were designed to establish an animal model analogous to human athyrotic cretinism without altering maternal thyroid status and subsequently to observe the natural course of the disorder. The effect of ovine intrauterine fetal thyroidectomy during the second trimester was assessed by following maternal thyroid function and amniotic fluid T4 by column [T4(C)], T3 by radioimmunoassay (T3RIA), and ovine TSH (oTSH). Maternal serum T4(C) rose during pregnancy but unexpectedly both T3RIA and oTSH decreased. In amniotic fluid, T4(C) and oTSH values were lower than maternal serum values and T3RIA was not detectable. Amniotic fluid T4(C) at Cesarean section was identical in cretin lambs and twin controls and was thus not a useful diagnostic tool. Athyrotic lambs showed gross physical, behavioral, and pathologic changes of cretinism and expired during the first day of life. At birth, cretin serum T4(C) and T3RIA were markedly decreased and oTSH was elevated. Normal lambs had a gradual decline in T4(C) levels until 10 weeks of age, but T3RIA values changed erratically. In addition, one cryptocretin with a thyroid remnant had a high normal T4(C) and elevated T3RIA and oTSH at birth. Her course was normal until 7 months of age when hypothyroidism suddenly developed. These observations could prove relevant in the interpretation of thyroid function of normal versus partially or completely athyrotic human infants.