Nuclear binding and cellular metabolism of thyroxine in a euthyroid patient with hyperthyroxinaemia.

The receptor mechanism and intracellular T4 deiodination were studied in a patient, who was euthyroid despite high T4 levels. Serum T3 and serum reverse T3 levels were normal and the TRH tests produced a normal rise in TSH. Protein binding capacities for T4 in serum were found to be normal. The T4 bound to a single set of binding sites in the patient's lymphocyte nuclei with a Ka which was depressed as compared with that of normals (Ka = 2.8 x 10(10) 1/mol) and a maximum specific binding capacity (MSBC = 1.9 fmol T4/10 micrograms DNA) which was increased as compared with normals (msbc = 1 x 10(-16) mol/1 T4/10 micrograms DNA). The cellular deiodination of T4 was found to be normal, whereas T3 accumulation was increased and the nuclear T3 concentration raised. In conclusion, these results suggest that in this patient the syndrome of peripheral tissue resistance to thyroid hormone action is due to a defect at the level of the nuclear receptor and not to a defective intracellular T4 to T3 conversion.