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[Thyroid hormone resistance syndromes: clinical aspects]
V Vlaeminck-Guillem1, J L Wémeau
1Clinique endocrinologique Marc-Linquette, USNA CHRU de Lille, France.
Introduction:
Syndromes of resistance to thyroid hormone correspond to variable clinical states which are usually transmitted as autosomal dominant traits and characterized by the lack of sensitivity of target tissues to triiodothyronine (T3). The diagnosis has to be performed in order to offer an appropriate therapy.
Current Knowledge And Key Points:
Clinical states range between two extremes: the generalized form, with global euthyroidism, and the predominantly pituitary form, with thyrotoxicosis. Surprisingly, these various clinical situations are usually determined by the same genetic defect, i.e., an anomaly of one of the two alleles of the gene encoding the thyroid hormone receptor TR beta. High levels of circulating thyroid hormones in the presence of detectable thyroid stimulating hormone (TSH) levels is the characteristic biological feature. Pituitary thyreotropic adenoma, another etiology of inappropriate secretion of TSH, needs thus to be ruled out. No treatment is required in case of generalized resistance to thyroid hormone, whereas two specific drugs (TRIAC and D-T4) appear to be useful in the predominantly pituitary form.
Future Prospects And Projects:
Mechanisms of resistance have been well documented, therefore allowing better understanding of T3 action on its nuclear receptor. Several transcriptional cofactors or corepressors have been identified and have to be investigated to explain the intriguing inter- and intra-familial, and even intra-individual, phenotypic variability. New insights should, furthermore, be gained from these studies to precisely determine how therapeutic agents work in resistance to thyroid hormone.
Insights
Thyroid hormone resistance syndromes involve target tissue insensitivity to triiodothyronine (T3), often due to genetic defects in the thyroid hormone receptor beta gene. Diagnosis is crucial for appropriate management, with varying treatments based on clinical presentation.
Area of Science:
- Endocrinology
- Genetics
- Molecular Biology
Background:
- Thyroid hormone resistance (TR) syndromes present diverse clinical states, typically autosomal dominant, marked by reduced tissue sensitivity to triiodothyronine (T3).
- These syndromes stem from genetic defects in the thyroid hormone receptor beta (TR beta) gene, affecting T3 binding and action.
- Key biological feature: elevated circulating thyroid hormones with detectable thyroid-stimulating hormone (TSH), necessitating differentiation from pituitary thyreotropic adenoma.
Purpose of the Study:
- To elucidate the clinical and genetic aspects of thyroid hormone resistance syndromes.
- To differentiate TR syndromes from other causes of abnormal TSH levels.
- To guide appropriate therapeutic strategies based on clinical phenotypes.
Main Methods:
- Clinical phenotyping of patients with variable resistance to thyroid hormone.
- Genetic analysis of the thyroid hormone receptor beta (TR beta) gene.
- Biochemical assessment of thyroid hormone levels and TSH.
Main Results:
- Identified genetic anomalies in the TR beta gene as the common cause for diverse clinical presentations of TR.
- Characterized distinct clinical states, ranging from generalized resistance with euthyroidism to pituitary resistance with thyrotoxicosis.
- Established elevated thyroid hormones with detectable TSH as a hallmark, requiring exclusion of pituitary adenoma.
Conclusions:
- Understanding TR mechanisms enhances knowledge of T3 action via its nuclear receptor.
- Investigating transcriptional cofactors is key to explaining phenotypic variability.
- Further research will refine therapeutic approaches for TR syndromes.
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