Work

Neonatal compressive goiter as the initial presentation of thyroid hormone resistance with dual THRB and TSHR mutations

Year: 2026

Type: article

Abstract: Resistance to thyroid hormones (RTH) is a rare disorder mostly caused by mutations in the thyroid hormone receptor β gene (THRB). It typically presents in late childhood or adulthood with elevated free thyroid hormone levels, inappropriately normal or high thyroid-stimulating hormone (TSH), and goiter. We report a case of RTH associated with a compressive neonatal goiter. A preterm newborn presented with respiratory distress due to a large goiter (9.7 mL; normal, <1.53 mL) requiring mechanical ventilation, as well as supraventricular tachycardia. His thyroid hormone profile was consistent with RTH: TSH, 73.8 mIU/L (normal range [NR], 1.5-15.6 mIU/L); free T4, 77.1 pmol/L (59.9 pg/mL; NR, 11.6-36 pmol/L [9.0-28.0 pg/mL]), and free T3, >30 pmol/L (>19.5 pg/mL; NR, 3.5-7.8 pmol/L [2.3-5.1 pg/mL]). Genetic testing and functional analyses identified a de novo heterozygous THRB nonsense mutation and an inherited heterozygous missense activating mutation in the TSHR gene. Treatment with tiratricol reduced TSH levels and goiter size, allowing extubation after 17 days. At 4 years, the patient remains stable on tiratricol. We conclude that the activating TSH receptor mutation is responsible for the neonatal compressive goiter in the context of a loss of function in THRB.

Source: JCEM Case Reports

DOI: 10.1210/jcemcr/luag316

Authors: Séverine Dubois, Frédérique Savagner, Alice Heneau, Ahlam Azar-Kolakez, Issam Al-Amir, Jean-Claude Carel