Introduction: Syndromes of resistance to thyroid hormone correspond to variable clinical states which are usually transmitted as autosomal dominant traits and characterized by the lack of sensitivity of target tissues to triiodothyronine (T3). The diagnosis has to be performed in order to offer an appropriate therapy.
Current knowledge and key points: Clinical states range between two extremes: the generalized form, with global euthyroidism, and the predominantly pituitary form, with thyrotoxicosis. Surprisingly, these various clinical situations are usually determined by the same genetic defect, i.e., an anomaly of one of the two alleles of the gene encoding the thyroid hormone receptor TR beta. High levels of circulating thyroid hormones in the presence of detectable thyroid stimulating hormone (TSH) levels is the characteristic biological feature. Pituitary thyreotropic adenoma, another etiology of inappropriate secretion of TSH, needs thus to be ruled out. No treatment is required in case of generalized resistance to thyroid hormone, whereas two specific drugs (TRIAC and D-T4) appear to be useful in the predominantly pituitary form.
Future prospects and projects: Mechanisms of resistance have been well documented, therefore allowing better understanding of T3 action on its nuclear receptor. Several transcriptional cofactors or corepressors have been identified and have to be investigated to explain the intriguing inter- and intra-familial, and even intra-individual, phenotypic variability. New insights should, furthermore, be gained from these studies to precisely determine how therapeutic agents work in resistance to thyroid hormone.