TOXIC THYROID ADENOMA - ABSENCE OF DNA MUTATIONS OF THE TSH RECEPTOR AND GS-ALPHA

DNA point mutations of the TSH receptor and of the a: subunit of the s timulatory GTP-binding protein (Gs alpha) have been suggested as major causes of hyperfunctioning thyroid adenomas. However, significant dif ferences in the prevalence of these mutations (from 0.3 to 84%) have b een found in different populations. The present study was designed to evaluate further the presence of mutations in discrete fragments of cD NA encoding critical regions of the TSH receptor and of the Gs alpha i nvolved in signal transduction and cAMP production. Genomic DNA extrac ted from 15 thyroid adenomas and surrounding quiescent thyroid tissues was used as a template to amplify four DNA fragments of TSH receptor and one DNA fragment of Gs alpha. TSH receptor and Gs alpha DNAs were analyzed by a number of techniques. We did not detect any mutations (n ew or previously described) in our patients. These results confirm tha t the causes of solitary toxic adenomas are protean, and only some of them may be somatic DNA point mutations. Since the clinical features o f solitary toxic adenoma are homogeneous, it could be important to est ablish the specific molecular defect underlying each case, in order to follow up the patients and to assess their clinical evolution.