Fetal loss associated with excess thyroid hormone exposure

Area of Science:

• Endocrinology
• Reproductive Medicine
• Genetics

Background:

• Maternal thyroid disorders significantly impact pregnancy outcomes.
• Studying fetal thyrotoxicosis is challenging as direct fetal hormone assessment is limited.
• Resistance to thyroid hormone (RTH) offers a model to study TH excess effects on the fetus.

Purpose of the Study:

• To investigate the impact of excessive thyroid hormone (TH) exposure on fetuses carried by mothers with RTH.
• To assess pregnancy outcomes in mothers with RTH who are otherwise euthyroid.
• To determine if high maternal TH levels lead to fetal thyrotoxicosis.

Main Methods:

• Retrospective analysis of 167 individuals from an Azorean family with RTH.
• Genotyping confirmed the Arg243-->Gln mutation in the TH receptor beta gene in affected individuals.
• Comparison of pregnancy outcomes, birth weights, and neonatal TSH levels between affected mothers, affected fathers, and unaffected relatives.

Main Results:

• Affected mothers exhibited a significantly higher miscarriage rate (22.9%) compared to controls (2.0%-4.4%).
• Unaffected infants born to affected mothers had lower birth weights (mean SD score -1.79) and undetectable TSH levels.
• Affected mothers had a trend towards more affected offspring (20 affected vs. 11 unaffected).

Conclusions:

• High miscarriage rates in mothers with RTH may disproportionately affect unaffected fetuses.
• Excess maternal TH levels in RTH cause fetal thyrotoxicosis, evidenced by low birth weight and suppressed TSH in unaffected infants.
• These findings suggest a direct toxic effect of thyroid hormone excess on fetal development.