Endocrine Abstracts

Resistance to thyroid hormones (RTH), is with the exceptions caused by mutations in the gene coding β₁-subunit of the thyroid receptor (TRβ₁) located on chromosome 3. More than 700 individuals with RTH belonging to about 250 families have been identified up to date. The presence of goiter, tachycardia and hyperactivity together with abnormal findings on routine thyroid testing usually lead to further investigation and, ultimately, the diagnosis of RTH. Characteristic thyroid function tests are elevated fT4 and fT3 concentrations with non-suppressed TSH levels. Aproximatelly 1/3 of all reported patients with RTH had the data of some therapeutic approach with the aim of lowering the thyroid hormones levels (antithyroid drugs, radioiodine therapy, surgery) in consequence of the initial erroneous diagnosis of thyrotoxicosis.

Authors present four families with RTH. Two adult probands experienced iatrogenic therapeutic approach (repeated subtotal thyroidectomy in one patient, respectively antithyroid therapy with propylthiouracil in another patient), early accurate diagnosis in two children (also treated with antithyroid drugs) prevented potential irreversible outcomes of the surgery in future. Molecular analysis of TRβ₁ demonstrated a novel heterozygous missence mutation F451L in exon 10 in 22-yr old male patient on long-term antithyroid therapy and his three clinically euthyroid siblings (two brothers and father). Already known mutation A317T was found in 62- old male patient after two operations on thyroid gland, any other siblings were available. Another two already known mutations V336M and R438C confirmed the diagnosis of RTH in 7-year old boy and his father, and in 5-year old boy and his mother, respectively.

Trends toward the radicality in indications to the surgery as well as in the operation radicality itself emphasize the importance of the watchfull differencial diagnostic aproach of the hyperthyroid states. Despite of relatively low incidence, in a case an elevated level of serum fT4 together with non-suppressed TSH levels it is of the importance to think of the diagnosis of RTH.