A clinician’s guide to understanding resistance to thyroid hormone due to receptor mutations in the TRα and TRβ isoforms
Open accessAbstract
There are two genes that express the major thyroid hormone receptor isoforms. Mutations in both these genes have given rise to Resistance to Thyroid Hormone (RTH) syndromes (RTHβ, RTHα) that can have variable phenotypes for mutations of the same receptor isoform as well as between the two receptor isoforms. In general, the relative tissue-specific distribution of TRβ and TRα determine RTH in different tissues for each form of RTH. These differences highlight some of the isoform-specific roles of each TR isoform. The diagnosis of RTH is challenging for the clinician but should be considered whenever a patient presents with unexplained elevated serum free T 4 (fT 4 ) and unsuppressed TSH levels, as well as decreased serum free T 4 /T 3 ratio. Here we provide a guide for the clinician to diagnose and treat both types of RTH.
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Type B thyroid hormone resistance has a familial component in 80% to 90% of cases.
“particularly due to the fact that a considerable proportion, ranging from 80% to 90%, of type B THR cases exhibit a familial component.87”
From Refractory hypothyroidism: unraveling the complexities of diagnosis and management (2023) · cites this paper as [87]
Loss-of-function mutations in THRs produce elevated circulating T4 and T3 levels simultaneously with signs of a functional peripheral hypothyroidism.
“Loss-offunction mutations in THRs have been shown to produce elevated circulating T4 and T3 levels simultaneously with signs of a functional peripheral hypothyroidism”
From Pharmacodynamic and Therapeutic Actions of Levothyroxine (2021) · cites this paper as [17]
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- Authors
- Singh, B. K., & Yen, P. M.
- Affiliations
- National University of Singapore (SG)
- Corresponding author
- Yen, Paul M.
- Venue
- Clinical Diabetes and Endocrinology
- Published
- 2017-09-15
- Volume
- 3
- Issue
- 1
- Pages
- 8-8
- ISSN
- 2055-8260 (ISSN-L)
- PMC
- PMC5603052
- OpenAlex
- W2755471567
- Cited by
- 72
- References
- 56
- Citations by year
- 2026: 8 · 2025: 13 · 2024: 9 · 2023: 13 · 2022: 6 · 2021: 8 · 2020: 5 · 2019: 6 · 2018: 3
- FWCI
- 3.02
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Clinical Diabetes and Endocrinology (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Medical Research Council (CSA 0054/2013, CIRG 16May028)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Cancer Diagnosis and Treatment
- Keywords
- thyroid hormone resistance, TRα, thyroid hormone receptor beta
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