Hypercholesterolemia in two siblings with resistance to thyroid hormones due to disease-causing variant in thyroid hormone receptor (THRB) gene

Pajek, Maja (author), Avbelj Stefanija, Magdalena (author), Trebušak Podkrajšek, Katarina (author), Šuput Omladič, Jasna (author), Žerjav-Tanšek, Mojca (author), Battelino, Tadej (author), Grošelj, Urh (author)

Resistance to thyroid hormone beta (RTHβ) is a syndrome characterized by a reduced response of target tissues to thyroid hormones. In 85% of cases, a pathogenic mutation in the thyroid hormone receptor beta (THRB) gene is found. The clinical picture of RTHβ is very diverse; the most common findings are goiter and tachycardia, but the patients might be clinically euthyroid. The laboratory findings are almost pathognomonic with elevated free thyroxin (fT4) levels and high or normal thyrotropin (TSH) levels; free triiodothyronin (fT3) levels may also be elevated. We present three siblings with THRB mutation (heterozygous disease-variant c.727C>T, p.Arg243Trp); two of them also had hypercholesterolemia, while all three had several other clinical characteristics of RTHβ. This is the first description of the known Slovenian cases with RTHβ due to the pathogenic mutation in the THRB gene. Hypercholesterolemia might be etiologically related with RTHβ, since the severity of hormonal resistance varies among different tissues and hypercholesterolemia in patients with THRB variants might indicate the relatively hypothyroid state of the liver. We suggest that cholesterol levels are measured in all RTHβ patients.

• Language: English
• Keywords: thyroid, resistance to thyroid hormones, RTHβ, thyroid hormone receptor, THRB, hypothyroidism, hypercholesterolemia
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: MF - Faculty of Medicine
• Publication status: Published
• Publication version: Version of Record
• Year: 2020
• Number of pages: 6 str.
• Numbering: Vol. 56, iss. 12, art. 699
• PID: 20.500.12556/RUL-134843
• UDC: 616-053.2ž
• ISSN on article: 1648-9144
• DOI: 10.3390/medicina56120699
• COBISS.SI-ID: 45814787
• Publication date in RUL: 04.02.2022

Record is a part of a journal

• Title: Medicina
• Publisher: MDPI
• ISSN: 1648-9144
• COBISS.SI-ID: 6754623

Licences

• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.
• Licensing start date: 15.12.2020

Projects

• Funder: ARRS - Slovenian Research Agency
• Project number: J3-2356
• Name: Izražanje in funkcionalna analiza nekodirajočih RNA pri parkinsonovi bolezni

• Funder: ARRS - Slovenian Research Agency
• Project number: P3-0343
• Name: Etiologija, zgodnje odkrivanje in zdravljenje bolezni pri otrocih in mladostnikih