DETECTION OF AN ACTIVATING MUTATION OF THE THYROTROPIN RECEPTOR IN A CASE OF AN AUTONOMOUSLY HYPERFUNCTIONING - THYROID INSULAR CARCINOMA

Thyroid carcinomas, even when well differentiated, usually appear as h ypofunctioning at scintigraphy. We report a case of an aggressive insu lar thyroid carcinoma presenting as an autonomously functioning thyroi d nodule and causing severe thyrotoxicosis. The tumor was metastatic t o a cervical lymph node and both lungs. An activating mutation of the TSH receptor gene in both the primary tumor and the lymph node metasta sis was found, due to a base substitution at codon 633 (normal guanine at position 1896 replaced by cytosine CAC for GAC causing aspartic ac id substitution by histidine). Other known oncogenes (gsp, ras, PTC/re t, trk, net, and p53) were not involved. This is the first description of an activating TSH receptor mutation in a thyroid hyperfunctioning carcinoma in which an aggressive malignant phenotype coexisted with ac tivation of the cAMP cascade and differentiated thyroid functions.