Syndromes of resistance to thyroid hormone: clinical considerations

Introduction. - Syndromes of resistance to thyroid hormone correspond to va riable clinical states which are usually transmitted as autosomal dominant traits and characterized by the lack of sensitivity of target tissues to tr iiodothyronine (T3). The diagnosis has to be performed in order to offer an appropriate therapy. Current knowledge and key points. - Clinical states range between two extre mes: the generalized form, with global euthyroidism and the predominantly p ituitary form, with thyrotoxicosis. Surprisingly, these various clinical si tuations are usually determined by the same genetic defect, i.e., an anomal y of one of the two alleles of the gene encoding the thyroid hormone recept or TR beta. High levels of circulating thyroid hormones in the presence of detectable thyroid stimulating hormone (TSH) levels is the characteristic b iological feature. Pituitary thyreotropic adenoma, another etiology of inap propriate secretion of TSH, needs thus to be ruled out. No treatment is req uired in case of generalized resistance to thyroid hormone, whereas two spe cific drugs (TRIAC and D-T4) appear to be useful in the predominantly pitui tary form. Future prospects and projects. - Mechanisms of resistance have been well do cumented, therefore allowing better understanding of T3 action on its nucle ar receptor. Several transcriptional cofactors or corepressors have been id entified and to be investigated to explain the intriguing inter- and intra- familial, and even intra-individual, phenotypic variability. New insights s hould, furthermore, be gained from these studies to precisely determine how therapeutic agents work in resistance to thyroid hormone. (C) 1999 Edition s scientifiques et medicales Elsevier SAS.