Resistance to Thyroid Hormone Beta in a Patient Born to a Mother With Undiagnosed Graves’ Disease

BACKGROUND/OBJECTIVE: Graves’ disease is an autoimmune disease associated with high levels of circulating thyroid hormones (THs). Resistance to thyroid hormone beta (RTHβ) caused by mutations in the thyroid hormone receptor beta (THRB) gene also can lead to high TH levels. Here, we describe 2 related cases, one of a woman with Graves’ disease, and her newborn with RTHβ. CASE REPORT: The woman was 27 years of age, with free thyroxine (T4) (FT4) >7.7 ng/dL (0.8-1.8), triiodothyronine of 1350 ng/dL (90-180), and undetectable thyrotropin (TSH), but no symptoms of thyrotoxicosis. She also had thyroglobulin antibodies of 65 (2-38). She was treated with methimazole and atenolol. The newborn neonatal screen showed a TSH of 43 mU/L [upper limit of normal 20 mU/L] and total T4 of 21.8 μg/dL (upper limit of normal 15). At 6 days of age, the newborn had a FT4 of 12.3 ng/dL (0.9-2.3), and unsuppressed TSH. The infant, at 3.5 months of age, was identified to harbor a THRB mutation (R438H) inherited from her father, but the brothers and mother had no THRB mutation. The newborn had tachycardia and delayed growth and was treated with atenolol and supplemental feeding, resulting in weight gain and reduced heart rate. DISCUSSION: The perinatal high FT4 and tachycardia could have been influenced by the elevated TH levels of the mother and the fetal RTHβ. CONCLUSION: It is difficult to evaluate the etiology of neonatal hyperthyroidism when fetal RTHβ and maternal Graves’ disease are not diagnosed early at birth.