Prenatal Diagnosis of Thyroid Hormone Resistance

A 29-yr-old woman with pituitary resistance to thyroid hormones (PRTH) was found to harbor a novel point mutation (T337A) on exon 9 of the thyroid hormone receptor β (TRβ) gene. She presented with symptoms and signs of hyperthyroidism and was successfully treated with 3,5,3′-triiodothyroacetic acid (TRIAC) until the onset of pregnancy. This therapy was then discontinued in order to prevent TRIAC, a compound that crosses the placental barrier, from exerting adverse effects on normal fetal development. However, as the patient showed a recurrence of thyrotoxic features after TRIAC withdrawal, we sought to verify, by means of genetic analysis and hormone measurements, whether the fetus was also affected by RTH, in order to rapidly reinstitute TRIAC therapy, which could potentially be beneficial to both the mother and fetus. At 17 weeks gestation, fetal DNA was extracted from chorionic villi and was used as a template for PCR and restriction analysis together with direct sequencing of the TRβ gene. The results indicated that the fetus was also heterozygous for the T337A mutation. Accordingly, TRIAC treatment at a dose of 2.1 mg/day was restarted at 20 weeks gestation. The mother rapidly became euthyroid, and the fetus grew normally up to 24 weeks gestation. At 29 weeks gestation mild growth retardation and fetal goiter were observed, prompting cordocentesis. Circulating fetal TSH was very high (287 mU/L) with a markedly reduced TSH bioactivity (B/I: 1.1 ± 0.4 vs 12.7 ± 1.2), while fetal FT4 concentrations were normal (8.7 pmol/L; normal values in age-matched fetuses: 5–22 pmol/L). Fetal FT3 levels were raised (7.1 pmo/L; normal values in age-matched fetuses: