Enhanced functional activity in thyroid adenomas in vitro

The majority of thyroid adenomas have been shown to be of clonal origin. In a portion of them, somatic or germline point mutations leading to altered TSH receptor or Gs alpha-proteins have been found. The constitutive activation of these proteins consecutively stimulate cAMP-levels. Expression of the TSH receptor mutants in mammalian cells leads to increased cAMP-production compared to cells transfected with the wild type receptor. Presently, the role of these mutations in the development and growth of such tumours is still unclear. In our own investigations we made an attempt to evaluate the functional significance of these observations. In nodular tissue derived from patients with functioning autonomous adenoma we found significantly higher basal and TSH stimulated thyroid hormone releasing activity than in the surrounding paranodular tissue and in thyroid tissue derived from patients with euthyroid goiter. These findings indicate a functional relevance of constitutively activated intracellular signal transducing cascade in thyroid adenomas that may lead to hyperthyroidism in the presence or absence of external thyroid stimulators.