Prenatal Diagnosis of Resistance to Thyroid Hormone and Its Clinical Implications.

CONTEXT

Resistance to thyroid hormone-β (RTH-β) is an autosomal dominant disorder characterized by reduced sensitivity of target tissues to thyroid hormones (THs). Individuals with RTH-β have high TH levels usually due to mutations in the TH receptor-β (THRB) gene. The management of RTH-β during pregnancy is challenging, as wild-type (WT) fetuses born to RTH-β mothers have low birth weight and suppressed postnatal thyroid-stimulating hormone (TSH), due to intrauterine exposure to excess TH.

OBJECTIVE

To determine birth weight and postnatal TSH of WT fetuses carried by mothers with RTH-β whose fT4 levels were maintained below 20% of the upper limit of normal (ULN).

DESIGN

Retrospective chart review.

SETTING

Academic institution in collaboration with off-site hospitals and private practices.

PATIENTS

Thirteen women harboring THRB gene mutations were evaluated during 18 pregnancies.

INTERVENTION

Prenatal genetic diagnosis by amniocentesis. Women carrying WT fetuses were given the option of treatment with antithyroid medication by their treating physicians with the aim to avoid serum fT4 levels above 20% of the ULN.

RESULTS

No significant difference was found in birth weight corrected for gestational age and in serum TSH levels at birth between WT and RTH-β infants born to RTH-β mothers.

CONCLUSIONS

Prenatal diagnosis may play an important role in the management of RTH-β during pregnancy. Aiming for maternal fT4 levels not above 50% of the ULN in RTH-β mothers carrying WT fetuses seems to be a prudent approach that prevents the otherwise expected low birth weight and postnatal TSH suppression.