Apparent resistance to thyroid hormones: From biological interference to genetics

Dieu, Xavier; Sueur, Guillaume; Moal, Valérie; Casson, F; Bouzamondo, Nathalie; Bouhours, Natacha; Briet, Claire; Illouz, Frédéric; Reynier, Pascal; Coutant, Régis; Rodien, Patrice; Mirebeau‐Prunier, Delphine

doi:10.1016/j.ando.2019.06.005

Cited by 10 publications

(9 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…On the other hand, biological interference was 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) [10], as it occurred in one of our cases. They stated that patients in whom biological discrepancy was due to analytic interference were more often asymptomatic, and patients with no identified etiology tended to be older [10], whilst we show one young patient with this condition.…”

Section: Discussionmentioning

confidence: 48%

“…Regarding the diagnosis, it would be recommendable to conduct a second thyroid function test (TSH, free T4, and free T3) with a different assay, and then screening for a genetic variant by sequencing the genes involved in thyroid hormone regulation, action and transport (THRB,THRA, SECISBP2, SLC16A, ALB, TTR, SERPI-NA7) [3,10].…”

Section: Discussionmentioning

confidence: 99%

“…RTH-β is an autosomal dominant disease, which has affected individuals who are heterozygous for mutant allele, although recessive heritance and 20-25 % of novo mutations have also been described [10]. On the other hand, gene defects remain unknown in 15 % of subjects with a phenotype similar to RTH-β, called "nonthyroid receptor-resistance to thyroid hormone (TR-RTH)".…”

Section: Introductionmentioning

confidence: 99%

“…Thyroid antibodies may be present in 20 % of these patients [14,15]. Clinical presentation needs to be differentiated with TSH secreting adenoma, familial hypertyrosinemia, hypalbuminemia, abnormalities in proteins such as albumin and thyroglobulin [10].…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Thyroid Hormone Resistance: Multicentrical Case Series Study

Mata¹,

Jiménez

Lopez³

et al. 2022

Horm Metab Res

View full text Add to dashboard Cite

Resistance to thyroid hormone syndrome (RTHS) is defined as increased thyroxine and triiodothyronine associated with normal or increased thyrotropin. This is usually due to a pathogenic variant of the gene coding for thyroid hormone receptor B (THRB). THRB is a rare genetic disorder characterized by an altered response of target tissue to the thyroid hormone action. Retrospective cross-sectional observational study with diagnosis of RTHS evaluated in secondary and tertiary hospitals for 6 years, from 2014 to 2020, in order to describe variables including age, sex, anthropometric data, clinical and biochemical characteristics of patients, who were divided according to age, in a pediatric group from 0 to 14 years (index cases), and an adult group composed of adult relatives of index cases. A molecular analysis of the THRB gene was performed. The total retrospective cohort included 7 pediatric patients and 15 adults. We found 22 cases with a clear male predominance (14/22). Mean age is 24.8 years old (22 days-70 years). Patients were referred because of symptoms 18.2% (4/22), analysis results 22.7% (5/22), or familial study 59.1% (13/22). About 31.8% (7/22) cases show goiter, 31.8% (7/22) sympathetic symptoms and 13.6% (3/22) abnormalities in behavior. In most cases, 77.3%, (17/22) show familial background of thyroid abnormalities. It is important to remark that 18.2% (4/22) relatives received previous incorrect treatments such as thyroidectomy, because of wrong diagnosis. In conclusion, a better understanding of RTHS, its prompt molecular diagnosis and genetic counseling, could avoid unnecessary tests and inappropriate treatments.

show abstract

Section: Discussionmentioning

confidence: 48%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Thyroid Hormone Resistance: Multicentrical Case Series Study

Mata¹,

Jiménez

Lopez³

et al. 2022

Horm Metab Res

View full text Add to dashboard Cite

show abstract

“…The main source of uncertainty was the conflicting results of TFTs in two affected individuals, who were revealed to actually have high fT3 and fT4 levels only when measured by alternative one-step immunoassays such as Roche and Beckman and one two-step method (Wallac DELFIA Perkin-Elmer), while normal TFTs were observed on Siemens and Vitros platforms. It is generally believed that, in patients with suspect of central hyperthyroidism, the presence of inconsistent results between different assay methods should be attributed to spurious hyperthyroxinemia due to serum interference [13]. Conversely, to the best of our knowledge, an underestimation of fT3 and fT4 in patients with a genuine central hyperthyroidism has never been described so far.…”

Section: Discussion/conclusionmentioning

confidence: 99%

Clinical Consequences of Variable Results in the Measurement of Free Thyroid Hormones: Unusual Presentation of a Family with a Novel Variant in the THRB Gene Causing Resistance to Thyroid Hormone Syndrome

Campi¹,

Agostini²,

Marelli³

et al. 2021

Eur Thyroid J

View full text Add to dashboard Cite

Introduction: Resistance to thyroid hormone β (RTHβ) is an inherited syndrome caused by dominant negative variants in the THRB gene (NM_000461.5). The clinical picture of RTHβ is variable, and patients harboring the same variant may display different degrees of disease severity. Case Presentation: A 30-year-old man presented with thyrotoxicosis and central hyperthyroidism and was found to have a novel variant in the exon 10 of THRB gene (c.C1282G, p.L428V), located within the third hot spot region of the C-terminal of the receptor. Surprisingly, the same variant was found in two other relatives with an apparent normal thyroid function at initial screening. After exclusion of a TSH-secreting adenoma and serum interference in the proband, and the finding that exogenous levothyroxine failed to suppress the TSH in the brother affected by nodular goiter, relatives’ thyroid function tests (TFTs) were reassessed with additional analytical method revealing biochemical features consistent with RTHβ in all carriers of the p.L428V variant. Functional studies showed a slightly impaired in vitro transcriptional activity of p.L428V. Interestingly‚ the expression of the human p.L428V thyroid hormone receptor beta in the zebrafish embryo background generated a phenotype consistent with RTHβ. Conclusion: Variable results of TFTs on some immunoassays can be a cause of RTHβ diagnostic delay, but the genotype-phenotype correlation in this family and functional studies support p.L428V as a novel THRB variant expanding the spectrum of gene variants causing RTHβ. In vivo, rather than in vitro, functional assays may be required to demonstrate the dominant negative action of THRB variants.

show abstract