CLINICAL CONSEQUENCES OF ACTIVATING GERMLINE MUTATIONS OF TSH RECEPTOR, THE CONCEPT OF TOXIC HYPERPLASIA

Activating mutations of TSH-R have been described in toxic nodules and more recently in familial nonautoimmune thyrotoxicosis, This last ent ity is still confused with familial Graves' disease and the aim of thi s study is to define its phenotype. Based on 49 patients coming from o ur first family and on the 4 other kindreds secondarily described in t he literature, the phenotypic expression is: a high incidence of hyper thyroidism, an early onset of disease, a higher men/women ratio (17/32 ) than in Graves' disease, the absence of ophthalmopathy and of circul ating and intrathyroid signs of immunity, a pathology similar to toxic nodule, the need for a total destruction of thyroid tissue to cure th e patients. The total analogy with toxic nodule leads us to name this new entity 'toxic hyperplasia'. Among 92 successive diffuse nonfamilia l thyrotoxicosis cases (initially considered as Graves) we isolated 5 cases without extra- and intrathyroidal autoimmunity, raising the ques tion of the existence of an apparent 'sporadic' form of toxic hyperpla sia (neomutation?).