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The Effect of Serum Dilution on Free Thyroxine (T₄) Concentration in the Low T₄ Syndrome of Nonthyroidal Illness

White Memorial Medical Center, Los Angeles, California 90033

Address requests for reprints to: Dr. Jerald Nelson, Endocrinology/Metabolism, White Memorial Medical Center, 1720 Brooklyn Avenue, Los Angeles, California 90033.

Progressive dilution of normal sera causes little change in free T₄ concentrations. Similar dilution of sera containing drug inhibitors of T₄ binding to serum proteins causes a progressive fall in free T₄. The low T₄ syndrome of nonthyroidal illness is thought to be associated with a circulating inhibitor(s) of T₄ binding. It would be expected, therefore, that dilution of sera from the low T₄ syndrome might also result in a fall in free T₄ concentrations. We compared the effect of progressive serum dilution on free T₄ concentrations in low T₄ syndrome sera to those in normal, hyperthyroid, pregnancy, TBG-deficient and salicylate-containing sera. A tracer dialysis method proved inappropriate for studying dilution effects. Using a new dialysate RIA method to measure free T₄, we found a progressive fall in free T₄ concentrations in sera from patients with the low T₄ syndrome similar to that in serum containing salicylate, but not to that in normal sera. The magnitude of the fall varied widely among individual patients. Free T₄ methods which use a diluted serum sample will underestimate free T₄ concentrations in the low T₄ syndrome.

Received October 16, 1984.

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