TY - JOUR
T1 - Defective Levothyroxine Response in a Patient with Dyshormonogenic Congenital Hypothyroidism Caused by a Concurrent Pathogenic Variant in Thyroid Hormone Receptor-β
AU - Lauffer, Peter
AU - Bikker, Hennie
AU - Garrelfs, Mark R
AU - Hillebrand, Jacquelien J G
AU - de Sonnaville, Marie-Louise C S
AU - Zwaveling-Soonawala, Nitash
AU - van Trotsenburg, A S Paul
N1 - Publisher Copyright: © Copyright 2021, Mary Ann Liebert, Inc., publishers 2021.
PY - 2021/11
Y1 - 2021/11
N2 - Background: Pituitary resistance to thyroid hormone (PRTH) is often seen in congenital hypothyroidism (CH), presenting as elevated thyrotropin (TSH) values despite (high-)normal thyroid hormone (TH) values achieved by levothyroxine treatment. In this study, we describe a girl with CH who was referred because of difficulties interpreting thyroid function tests. She was thought to have PRTH associated with CH, but genetic studies discovered a pathogenic variant in THRB, causing resistance to TH (RTH-β). Methods: Clinical, genetic, and biochemical data of the proband's family were collected. Results: The 3-year-old girl was diagnosed with CH due to a homozygous pathogenic c.470del p.(Asn157Thrfs*3) SLC5A5 variant in the neonatal period. She needed a notably high levothyroxine dose to normalize TSH, leading to high free thyroxine levels. There were no signs of hyperthyroidism. Sequencing identified a heterozygous pathogenic c.947G>A p.(Arg316His) THRB variant. Conclusions: To our knowledge, this is the first report of concomitant SLC5A5 and THRB variants causing CH and RTH-β.
AB - Background: Pituitary resistance to thyroid hormone (PRTH) is often seen in congenital hypothyroidism (CH), presenting as elevated thyrotropin (TSH) values despite (high-)normal thyroid hormone (TH) values achieved by levothyroxine treatment. In this study, we describe a girl with CH who was referred because of difficulties interpreting thyroid function tests. She was thought to have PRTH associated with CH, but genetic studies discovered a pathogenic variant in THRB, causing resistance to TH (RTH-β). Methods: Clinical, genetic, and biochemical data of the proband's family were collected. Results: The 3-year-old girl was diagnosed with CH due to a homozygous pathogenic c.470del p.(Asn157Thrfs*3) SLC5A5 variant in the neonatal period. She needed a notably high levothyroxine dose to normalize TSH, leading to high free thyroxine levels. There were no signs of hyperthyroidism. Sequencing identified a heterozygous pathogenic c.947G>A p.(Arg316His) THRB variant. Conclusions: To our knowledge, this is the first report of concomitant SLC5A5 and THRB variants causing CH and RTH-β.
KW - Child, Preschool
KW - Congenital Hypothyroidism/drug therapy
KW - Consanguinity
KW - Female
KW - Humans
KW - Pedigree
KW - Symporters
KW - Thyroid Hormone Receptors beta/genetics
KW - Thyroid Hormone Resistance Syndrome/genetics
KW - Thyroxine/therapeutic use
KW - Turkey
UR - http://www.scopus.com/inward/record.url?scp=85119978035&partnerID=8YFLogxK
U2 - https://doi.org/10.1089/thy.2021.0204
DO - https://doi.org/10.1089/thy.2021.0204
M3 - Article
C2 - 34382419
SN - 1050-7256
VL - 31
SP - 1757
EP - 1762
JO - Thyroid
JF - Thyroid
IS - 11
ER -