Most patients with resistance to thyroid hormone (RTH) test negative in newborn screening (NBS) for congenital hypothyroidism (CH). Here, we present a case of RTH diagnosed through NBS. The patient presented to us after her NBS for CH revealed high TSH (23.4 µIU/mL) and free T4 (FT4) (5.40 ng/dL) levels. Apart from tachycardia, she exhibited no other manifestations related to excess or deficiency of thyroid hormones. A confirmatory test replicated the findings, showing elevated serum TSH levels (35.7 µIU/mL) along with high FT4 levels (5.84 ng/dL). Ultrasonography showed marked thyroid gland enlargement (> +4 SD). Targeted next-generation sequencing of genes associated with genetic thyroid disorders revealed a previously reported THRB variant, p.Gly345Cys. Unexpectedly, two biallelic DUOX2 variants (p.His678Arg and p.Arg1334Trp) were also detected. At her last visit, no significant issues were observed with neurological development, growth, bone maturation, or gastrointestinal symptoms related to thyroid function at the age of 1 year, without treatment for RTH and CH. During follow-up, the TSH and FT4 levels gradually decreased. In conclusion, we report a patient with simultaneous RTH and DUOX2 defects, demonstrating the value of conducting a comprehensive analysis of multiple genes associated with thyroid diseases to better comprehend the pathogenesis in patients with atypical thyroid-related phenotypes.
Keywords: DUOX2; THRB; newborn screening; thyroid hormone resistance syndrome.
2024©The Japanese Society for Pediatric Endocrinology.