title: Thyroid gene expression in familial nonautoimmune hyperthyroidism shows common characteristics with hyperfunctioning autonomous adenomas.
abstract: BACKGROUND
  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.
  
  
  METHODS
  Functional phenotypes were determined in vitro and molecular phenotypes by hybridization on microarray slides.
  
  
  METHODS
  Nine patients with FNAH were investigated, six for functional in vitro study of the tissue and five for gene expression.
  
  
  RESULTS
  Iodide metabolism, H(2)O(2), 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.
authors.affiliation: Institute of Interdisciplinary Research, School of Medicine, Free University of Brussels, campus Erasme, 808 Route de Lennik, 1070 Brussels, Belgium.
authors.forename: Aline
authors.initials: A
authors.lastname: Hébrant
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Van Sande
authors.forename: Pierre P
authors.initials: PP
authors.lastname: Roger
authors.forename: Martine
authors.initials: M
authors.lastname: Patey
authors.forename: Marc
authors.initials: M
authors.lastname: Klein
authors.forename: Claire
authors.initials: C
authors.lastname: Bournaud
authors.forename: Frédérique
authors.initials: F
authors.lastname: Savagner
authors.forename: Jacques
authors.initials: J
authors.lastname: Leclère
authors.forename: Jacques E
authors.initials: JE
authors.lastname: Dumont
authors.forename: Wilma C G
authors.initials: WC
authors.lastname: van Staveren
authors.forename: Carine
authors.initials: C
authors.lastname: Maenhaut
mesh_terms: D000236:Adenoma / Q000150:complications / Q000235:genetics* / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D002648:Child; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D006980:Hyperthyroidism / Q000209:etiology / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D008969:Molecular Sequence Data; D020411:Oligonucleotide Array Sequence Analysis; D013961:Thyroid Gland / Q000378:metabolism*; D013964:Thyroid Neoplasms / Q000150:complications / Q000235:genetics* / Q000378:metabolism