CLINICAL AND HORMONAL OUTCOME AFTER 2 YEARS OF TRIIODOTHYROACETIC ACID TREATMENT IN A CHILD WITH THYROID-HORMONE RESISTANCE

We report here a new family with thyroid hormone resistance (RTH), wit h phenotypic variability among subjects. Particular emphasis is given to the clinical and hormonal outcome after 2 years of triiodothyroacet ic acid (TRIAC) treatment in an affected child with peripheral thyroto xic features (pituitary RTH [PRTH]). The genetic defect was a substitu tion in position 1642 (C to A) within the exon 10 of thyroid hormone r eceptor beta(1) (TR beta(1)) gene, resulting in the codon change P453T . The mutant receptor had a significantly reduced triiodothyronine (T3 ) binding affinity. Within this family, the child and the mother suffe red from hyperthyroidism and were clinically classified as PRTH, while the maternal grandmother was clinically euthyroid, indicating a gener alized form of the disease (GRTH). Rapid normalization of heart rate w as initially obtained by the association of the cardioselective beta-b locker atenolol with TRIAC. Nevertheless, long-term TRIAC therapy, thr ough its lowering action of serum thyrotropin (TSH) and thyroid hormon e levels, maintained a normal heart rate after atenolol discontinuatio n and normalized the neurological disturbances and the clinical signs in the child, without any apparent side effect. In fact, growth veloci ty remained unchanged and no alteration of several parameters of thyro id hormone action at the tissue level was observed, whereas soluble in terleukin-2 receptor levels improved significantly, confirming the saf ety and efficacy of long-term TRIAC therapy for PRTH also during child hood. We thus recommend testing the efficacy of TRIAC therapy in all R TH patients presenting with clinical features of hyperthyroidism.