ESPE Yearbook of Paediatric Endocrinology

Brief summary: In utero the embryo and the fetus are protected by different mechanisms from too high levels of maternal thyroid hormones after transplacental passage such as deiodination and sulfatation of T4 and T3 in the placenta as well as in the tissues of the unborn child (1,2). Maternal hyperthyroidism and its treatment with anti-thyroid drugs is associated with different congenital malformation. However, so far, it remains unclear, which malformations are linked to hyperthyroidism, to anti-thyroid drug toxicity, or anti-thyroid drug induced hypothyroidism in utero.

To shed light on the effects of hyperthyroidism in utero, Martinez et al. developed a Deiodinase 3 (Dio3^−/−) mouse strain. Embryos were exposed at the earliest stages to hyperthyroidism. Then, the authors performed a comprehensive phenotyping at different ages on all organ systems in Dio3^−/− mice. As a consequence of in utero exposure to elevated thyroid hormone levels mice developed reduced viability, severe growth retardation, and cartilage loss postnatally. Mice surviving the neonatal period showed cranial and cerebral malformations, such as hydrocephalus, choanal atresia, and cleft palate and cardiac problems such as septal defects and thin ventricular walls.

In conclusion, this study provides for the first time detailed new insights into developmental effects of thyrotoxicosis in utero and postnatally describing mainly specific cranio-cerebral and cardiac defects.

References: 1. Szinnai G, Polak M. Chapter 62: The maturation of thyroid function in the fetus, in the perinatal period and during childhood. In: Werner and Ingbar’s The Thyroid, 11^th edition 2020, Wolters Kluwers. 2. Bianco AC, Dumitrescu A, Gereben B, Ribeiro MO, Fonseca TL, Fernandes GW, Bocco BMLC. Paradigms of Dynamic Control of Thyroid Hormone Signaling. Endocr Rev. 2019 Aug 1;40(4):1000-1047. doi: 10.1210/er.2018-00275. PMID: 3103399.