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Journal of Pediatric Endocrinology and Metabolism

Editor-in-Chief: Kiess, Wieland

Ed. by Bereket, Abdullah / Darendeliler, Feyza / Dattani, Mehul / Gustafsson, Jan / Luo, Fei Hong / Toppari, Jorma / Turan, Serap Demircioglu

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Volume 28, Issue 5-6


Hypothyroidism caused by the combination of two heterozygous mutations: one in the TSH receptor gene the other in the DUOX2 gene

Mari Satoh / Keiko Aso / Sayaka Ogikubo / Atsuko Yoshizawa-Ogasawara / Tsutomu Saji
Published Online: 2014-09-16 | DOI: https://doi.org/10.1515/jpem-2014-0078


Subjects who are heterozygous for thyroid stimulating hormone receptor (TSHR) gene mutations present various phenotypes that range from euthyroid to hyperthyrotropinemia. Similarly, heterozygous dual oxidase 2 (DUOX2) gene mutations result in variable phenotypes, such as transient congenital hypothyroidism, subclinical hyperthyrotropinemia, and euthyroid in children. Here, we describe an 8-year-old boy who had normal newborn screening results, but who developed nonautoimmune hypothyroidism at the age of 1 year and 8 months of age. He was heterozygous for previously reported R450H-TSHR mutation and heterozygous for a novel double mutant allele A1323T-DUOX2 and L1343F-DUOX2. He needed levothyroxine (l-T4) replacement therapy to keep serum TSH levels within normal limits; l-T4 dose of 2.01–2.65 μg/kg/day corresponded to the dose taken by children homozygous for R450H-TSHR and by children with permanent congenital hypothyroidism. Therefore, the coexistence of a heterozygous TSHR mutation and a heterozygous DUOX2 mutation may have affected the severity of his hypothyroid condition.

Keywords: dual oxidase 2 (DUOX2); hypotyroidism; oligogenicity; TSH receptor


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About the article

Corresponding author: Mari Satoh, Department of Pediatrics, Toho University Omori Medical Center, 6-11-1 Omori-nishi, Ota-ku, Tokyo 143-8541, Japan, E-mail:

Received: 2014-02-13

Accepted: 2014-08-15

Published Online: 2014-09-16

Published in Print: 2015-05-01

Citation Information: Journal of Pediatric Endocrinology and Metabolism, Volume 28, Issue 5-6, Pages 657–661, ISSN (Online) 2191-0251, ISSN (Print) 0334-018X, DOI: https://doi.org/10.1515/jpem-2014-0078.

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