Neonatal compressive goiter as the initial presentation of thyroid hormone resistance with dual THRB and TSHR mutations.
6 affiliations
- 1APHP North, Paris City University, Pediatric Endocrinology and Diabetes, Rare Disease Center for Growth and Developmental Endocrine Diseases, Robert-Debré University Hospital, Paris 75019, France.
- 2Inserm U1141 NeuroDiderot, Paris City University, Paris F-75006, France.
- 3Laboratory of Biochemistry and Molecular Biology, IFB-CHU Purpan, Toulouse 31000, France.
- 4Inserm/UPS UMR 1297, I2MC, Institut des Maladies Métaboliques et Cardiovasculaires, , Toulouse 31432 Cedex 4, France.
- 5APHP North, Paris City University, Department of Neonatal Intensive Care Unit, Robert-Debré University Hospital, Paris 75019, France.
- 6APHP North, Paris City University, Laboratory of Biochemistry and Hormonology, Robert-Debré University Hospital, Paris 75019, France.
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.
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BibTeX
@article{dubois2026neonatal,
title = {{Neonatal compressive goiter as the initial presentation of thyroid hormone resistance with dual THRB and TSHR mutations.}},
author = {Séverine Dubois and Frédérique Savagner and Alice Heneau and Ahlam Azar-Kolakez and Issam Al-Amir and Jean-Claude Carel},
journal = {JCEM case reports},
year = {2026},
month = nov,
doi = {10.1210/jcemcr/luag316},
url = {https://europepmc.org/article/MED/42996815},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Neonatal compressive goiter as the initial presentation of thyroid hormone resistance with dual THRB and TSHR mutations.
AU - Séverine Dubois
AU - Frédérique Savagner
AU - Alice Heneau
AU - Ahlam Azar-Kolakez
AU - Issam Al-Amir
AU - Jean-Claude Carel
PY - 2026
DA - 2026/11/06
JO - JCEM case reports
DO - 10.1210/jcemcr/luag316
UR - https://europepmc.org/article/MED/42996815
AB - 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.
SN - 2755-1520
ER -