Triiodothyronine binding to lymphocyte nuclei and plasma cyclic AMP response to intravenous glucagon in patients with peripheral resistance to thyroid hormones

: In vitro studies of nuclear binding of triiodothyronine (T3) in lymphocytes were performed in three members of a family with hereditary peripheral resistance to thyroid hormone action. Ficoll-Hypaque purified lymphocytes were used; the binding characteristics were analyzed by Scatchard's methods. In 5 euthyroid subjects the apparent mean equilibrium association constant (Ka) was 6.2 x 10(9) l/mol and the mean maximal binding capacity (Cap) 14.4 x 10(-15) mol/100 microgram DNA. In the 3 members of the family one single set os saturable T3 nuclear binding sites with affinity constants similar to those in the controls (mean Ka = 3.2 x 10(9) l/mol; mean Cap = 17.4 x 10(-15) mol/100 microgram DNA) were found. The glucagon stimulated increase in plasma cyclic AMP was studied in 6 healthy subjects and the four members of the family. The plasma cyclic AMP levels of the patients with hormone resistance were generally within the normal range. These observations demonstrate that in these patients with peripheral resistance to thyroid hormone binding of T3 to the receptor in the nucleus of lymphocytes is normal; in relation to the high circulating thyroid hormone levels, the thyroid hormone mediated cyclic AMP response is disturbed, suggesting that the defect is at the post-receptor effector level.