DECREASED PERIPHERAL 3,5,3'-TRIIODOTHYRONINE (T-3) PRODUCTION FROM THYROXINE (T-4) - A SYNDROME OF IMPAIRED THYROID-HORMONE ACTIVATION DUE TO TRANSPORT INHIBITION OF T-4-PRODUCING INTO T-3-PRODUCING TISSUES

T-4, rT(3), and T-3 kinetic studies have been performed in a T-4-substituted female who showed an increased serum T-4/T-3 ratio and substantially increased rT(3) serum levels in the presence of normal serum thyroid hormone binding properties. The kinetic studies were performed to discriminate between T-4 transport inhibition into plasma T-3-producing tissues and inhibition of extrathyroidal T-4 to T-3 conversion. The principal findings were that both T-4 and rT(3) transport were inhibited into the rapid equilibrating pool (REP), which mainly consists of the liver. The plasma T-3 production rate was decreased. Despite an elevated serum free T-4 level, serum TSH was elevated, pointing to T-4 transport inhibition at the level of the thyrotroph as well. Transport of T-4 and rT(3) was normal to the slowly equilibrating pool, whereas no transport inhibition of T-3 was found to either pool. Because T-4 into T-3 conversion efficiency in the REP (the main source of plasma T-3 production) was normal, it was concluded that the lowered T-3 production in the subject was caused by transport inhibition of T-4 into the liver. Although the occurrence of the syndrome is rare, its significance is of general importance, in that it shows that transport of thyroid hormone may vary at the tissue level. Furthermore, as T-3 is the principal biologically active thyroid hormone, regulation of transport of T-4 into the REP may play a (patho)physiological role in the ultimate determination of thyroid hormone activity in the tissues.