[Thyroid hormone resistance: variable clinical manifestations in five patients]

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 than other tissues to thyroid hormones. More often, patients have peripheral tissue resistance as well and are euthyroid. RTH is related to point mutations in the T3-binding domain of the beta-receptor gene. We report the variable clinical and biochemical features of five patients with RTH.

Five patients with RTH were clinically and biochemically evaluated: thyroid tests were done at baseline, after TRH stimulation and after T3-suppression test. Thyroid ultrasound was performed as well. Individual exons of the thyroid hormone receptor beta gene were amplified from leucocyte DNA in these patients using the polymerase chain reaction (PCR).

Sequence analysis identified a single point mutation at a certain nucleotide position. This corresponds to aminoacids substitutions at one position in the predicted aminoacid sequence. RTH was familial in three individuals and sporadic in two. Three of the patients underwent thyroid surgery or radioiodine treatment because of recurrent goiter and/or "refractory hyperthyroidism". Moreover, one of our patients with RTH developed also hyperthyroidism due to Graves disease and underwent thyroid surgery for the third time. Her brother, besides RTH, demonstrated strongly positive TPO-antibodies and a hypoechogenic pattern on ultrasound. So the diagnosis of Hashimoto's thyroiditis was made.

RTH has to be considered in all patients with inappropriate TSH secretion. The clinical manifestation of patients with RTH is heterogenous. Thyroid antibody measurements should be performed regularly in order to detect the development of coexisting autoimmune thyroid disease.