Loss of Integrity of Thyroid Morphology and Function in Children Born to Mothers with Inadequately Treated Graves’ Disease

Abstract

Abstract Context: Central congenital hypothyroidism (CH-C) in neonates born to mothers with inadequately treated Graves’ disease usually needs T4 supplementation. The thyroid and its regulatory system have not yet been extensively studied after T4 withdrawal, until we observed disintegrated thyroid glands in some patients. Objective: The aim was to study the occurrence and pathogenesis of disintegrated thyroid glands in CH-C patients. Design, Setting, Patients, Participants: Thyroid function was measured and thyroid ultrasound imaging was performed in 13 children with CH-C due to inadequately treated maternal Graves’ disease after T4-supplementation withdrawal (group Aa). In addition, thyroid ultrasound imaging was performed in six children with CH-C born to inadequately treated mothers with Graves’ disease, in whom T4 supplementation was not withdrawn yet (group Ab) or never initiated (group Ac), in six euthyroid children born to adequately treated mothers with Graves’ disease (group B), and in 10 T4-supplemented children with CH-C as part of multiple pituitary hormone deficiency (group C). Main Outcome Measures: Thyroid function and aspect (volume, echogenicity, echotexture) were measured. Results: In group A, five children had developed thyroidal hypothyroidism characterized by persistently elevated TSH concentrations and exaggerated TSH responses after TRH stimulation. In the majority of patients in groups A and C, thyroid echogenicity and volume were decreased, and echotexture was inhomogeneous. Thyroid ultrasound imaging was normal in group B children. Conclusions: Inadequately treated maternal Graves’ disease not only may lead to CH-C but also carries an, until now, unrecognized risk of thyroid disintegration in the offspring as well. We speculate that insufficient TSH secretion due to excessive maternal-fetal thyroid hormone transfer inhibits physiological growth and development of the child’s thyroid.