THYROID-HORMONE RESISTANCE - VARIABLE CLI NICAL MANIFESTATIONS IN 5 PATIENTS

Aim: The syndrome of thyroid hormone resistance (RTH) is characterised by elevated circulating thyroid hormones, unsuppressed TSH levels and peripheral refractoriness to hormone action. Patients with RTH may be clinically hyperthyroid if the pituitary gland is more insensitive th an other tissues to thyroid hormones. More often. patients have periph eral tissue resistance as well and are euthyroid. RTH is related to po int mutations in the TS-binding domain of the beta-receptor gene. We r eport the variable clinical and biochemical features of five patients with RTH. Methods: Five patients with RTH were clinically and biochemi cally evaluated: thyroid tests were done at baseline, after TRH stimul ation and after T3-suppression test. Thyroid ultrasound was performed as well. Individual exons of the thyroid hormone receptor beta gene we re amplified from leucocyte DNA in these patients using the polymerase chain reaction (PCR). Results: Sequence analysis identified a single point mutation at a certain nucleotide position. This corresponds to a minoacids substitutions at one position in the predicted aminoacid seq uence. RTH was familiar in three individuals and sporadic in two. Thre e of the patients underwent thyroid surgery or radioiodine treatment b ecause of recurrent goiter and/or ''refractory hyperthyroidism''. More over, one of our patients with RTH developed also hyperthyroidism due to Graves' disease and underwent thyroid surgery for the third time. H er brother, besides RTH. demonstrated strongly positive TPO-antibodies and a hypoechogenic pattern on ultrasound. So the diagnosis of Hashim oto's thyroiditis was made. Conclusions: RTH has to be considered in a ll patients with inappropriate TSH secretion. The clinical manifestati on of patients with RTH is heterogenous. Thyroid antibody measurements should be performed regularly in order to detect the development of c oexisting autoimmune thyroid disease.