Apparent resistance to thyroid hormones: From biological interference to genetics

Autor: Régis Coutant, Xavier Dieu, Natacha Bouhours, Guillaume Sueur, Florence Boux de Casson, Frédéric Illouz, Delphine Mirebeau-Prunier, Pascal Reynier, Claire Briet, Valérie Moal, Nathalie Bouzamondo, Patrice Rodien
Přispěvatelé: Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Rok vydání: 2019
Předmět:
Male
Endocrinology
Diabetes and Metabolism
[SDV]Life Sciences [q-bio]
Thyrotropin
Thyroid Function Tests
medicine.disease_cause
0302 clinical medicine
Endocrinology
Child
ComputingMilieux_MISCELLANEOUS
Mutation
Triiodothyronine
biology
medicine.diagnostic_test
Thyroid
Thyroid Hormone Receptors beta
General Medicine
Middle Aged
3. Good health
medicine.anatomical_structure
Hormone receptor
030220 oncology & carcinogenesis
Child
Preschool
Female
medicine.symptom
Adult
Thyroid Hormone Resistance Syndrome
endocrine system
medicine.medical_specialty
Adolescent
030209 endocrinology & metabolism
Thyroid function tests
Asymptomatic
03 medical and health sciences
Internal medicine
medicine
Humans
Diagnostic Errors
Aged
business.industry
Infant
Transthyretin
Thyroxine
biology.protein
business
Carrier Proteins
Hormone
Zdroj: Annales d'Endocrinologie
Annales d'Endocrinologie, Elsevier Masson, 2019, 80 (5-6), pp.280-285. ⟨10.1016/j.ando.2019.06.005⟩
ISSN: 2213-3941
0003-4266
Popis: Resistance to thyroid hormones syndrome is defined as increased thyroxine (T4) and triiodothyronine (T3) concentrations associated with normal or sometimes increased thyrotropin (TSH) concentration. This is usually due to a pathogenic variant with loss of function of the gene coding for thyroid hormone receptor β (THRB). This discrepancy in thyroid hormones (TH) and TSH concentrations is also frequently observed in the presence of analytical interference, notably alteration of TH transport proteins in serum. During 2017, 58 samples were sent to our laboratory in the Angers University Hospital Rare Thyroid and Hormone Receptor Disease Reference Center in order to identify an etiology for discrepant TSH and TH results. We sequenced the genes involved in TH regulation, action and transport (THRB, THRA, SECISBP2, SLC16A, ALB, TTR, SERPINA7). Free T4 and free T3 assay were performed with a second immunoassay (Siemens ADVIA Centaur). A genetic cause of discrepancy in TH and TSH concentrations, with mutation in THRB, was found in 26% of cases (15/58). Biological interference due to TH serum transport protein variant was found in 24% (14/58) of cases. No pathogenic variants were found in the other genes studied. Biological interference was also suspected in 26% of cases without genetic variant, in which the biological discrepancy was not confirmed by a second analytical technique (15/58). Finally, no etiology for the biological discrepancy could be found in 24% of cases (14/58). Clinically, patients in whom biological discrepancy was due to analytic interference were more often asymptomatic, and patients with no identified etiology tended to be older. To limit diagnostic errors associated with the finding of discrepant TSH and TH, we recommend initially conducting a second thyroid function test (TSH, free T4 and free T3) with a different assay, and then screening for a genetic variant in gene coding for thyroid hormone receptor β (THRB) and the TH serum transport proteins (ALB, TTR, SERPINA7).
Databáze: OpenAIRE
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