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Thyroid Gene Expression in Familial Nonautoimmune Hyperthyroidism Shows Common Characteristics with Hyperfunctioning Autonomous Adenomas

Abstract :

Context: Dominant activating mutations of the TSH receptor are the cause of familial nonautoimmune hyperthyroidism (FNAH) (inherited mutations affecting the whole gland since embryogenesis) and the majority of hyperfunctioning autonomous adenomas (AAs) (somatic mutations affecting only one cell later in the adulthood).Objective: The objective of the study was defining the functional and molecular phenotypes of FNAH and comparing them with the ones of AA. Design: Functional phenotypes were determined in vitro and molecular phenotypes by hybridization on microarray slides. Patients: Nine patients with FNAH were investigated, six for functional in vitro study of the tissue and five for gene expression. Results: Iodide metabolism, H2O2, cAMP, and inositol phosphate generation in FNAH slices stimulated or not with TSH were normal. The mitogenic response of cultured FNAH thyrocytes to TSH was normal but more sensitive to the hormone. Gene expression profiles of FNAH and AAs showed that among 474 genes significantly regulated in FNAH, 93% were similarly regulated in AAs. Besides, 783 genes were regulated only in AAs. Bioinformatic analysis pointed out common down-regulations of genes involved in immune response, cell/cell and cell/matrix adhesions, and apoptosis. Pathways up-regulated only in AAs mainly involve diverse biosyntheses. These results are consonant with the larger growth of AAs than FNAH tissues. Conclusions: Whether hereditary or somatic after birth, activating mutations of the TSH receptor have the same qualitative consequences on the thyroid cell phenotype, but somatic mutations in AAs have a much stronger effect than FNAH mutations. Both are variants of one disease: genetic hyperthyroidism.

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https://hal.univ-angers.fr/hal-03275655
Contributeur : Okina Université d'Angers <>
Soumis le : jeudi 1 juillet 2021 - 12:29:55
Dernière modification le : vendredi 2 juillet 2021 - 03:30:39

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Aline Hébrant, Jacqueline van Sande, Pierre P. Roger, Martine Patey, Marc Klein, et al.. Thyroid Gene Expression in Familial Nonautoimmune Hyperthyroidism Shows Common Characteristics with Hyperfunctioning Autonomous Adenomas. Journal of Clinical Endocrinology and Metabolism, Endocrine Society, 2009, 94 (7), pp.2602 - 2609. ⟨10.1210/jc.2008-2191⟩. ⟨hal-03275655⟩

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