THE EXTRACELLULAR THYROTROPIN RECEPTOR DOMAIN IS NOT A MAJOR CANDIDATE FOR MUTATIONS IN TOXIC THYROID-NODULES

Constitutive activation of the cyclic adenosine monophosphate (cAMP) c ascade by either thyrotropin receptor (TSHR) or gsp mutations is consi dered to be the major molecular cause of toxic thyroid nodules (TTNs). In a recent study we investigated a consecutive series of 31 TTNs and identified 15 somatic TSHR mutations (n = 14 in exon 10; n 1 in exon 9) but no mutations in gsp exons 7-10 (3). The purpose of the present study was to determine whether the extracellular TSHR domain would be a candidate for mutations causing TTNs. Therefore, we screened TSHR ex ons 1-8 in the remaining 16 TTNs without mutations in TSHR exons 9 and 10 and gsp exons 7-10 of our previous study. Except for a known funct ional polymorphism in exon 1 (Pro 52 Thr) in 2 TTNs and a silent base exchange in exon 7 (187 Asn) in 7 other TTNs no TSHR mutations were id entified. To clarify the molecular etiology of TTNs without TSHR or gs p mutations, candidate genes. in other steps of the cAMP cascade have to be considered.