Toxic thyroid adenomas are well-encapsulated homogeneous neoplasia secreting thyroid hormones in the absence of a TSH stimulus. As the secreted hormones inhibit the pituitary thyrotrophs, TSH plasma levels decrease and the normal tissue becomes quiescent. Thyroid adenomas are monoclonal, i.e. are constituted by the progeny of one mutated cell, and therefore result from a single initial biochemical lesion.
Our group has demonstrated the mitogenic role of the cyclic AMP cascade in the thyroid (1, 2). Permanent stimulation of this cascade by a constitutive adenosine receptor (A2a) or a mutated Gs protein, which are coupled positively to adenylate cyclase in transgenic mice, leads to the formation of an autonomous hyperfunctioning adenoma involving the whole thyroid (3, 4). Gain-of-function activating mutations of the TSH receptor (TSH-R) or of the G protein (Gs), which stimulate adenylate cyclase, have been demonstrated in human autonomous thyroid adenoma (5–9). Activating germline mutations of the TSH receptor