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Effect of Free Fatty Acids on the Concentration of Free Thyroxine in Human Serum: The Role of Albumin^*

CARL M. MENDEL, PHILIP H. FROST and RALPH R. CAVALIERI

Cardiovascular Research Institute and the Department of Medicine, University of California San Francisco, California 94143
Endocrine-Metabolism Section and Nuclear Medicine Service, Veterans Administration Medical Center and University of California San Francisco, California 94121

Address all correspondence and requests for reprints to: Carl M. Mendel, M.D. Cardiovascular Research Institute M -1327 University of California, San Francisco, California 94143.

The concentration of FFA in normal human plasma in vivo generally ranges between 0.2 and 0.7 meq/liter; slightly higher concentrations have occasionally been reported in patients who are seriously ill. To determine whether such FFA concentrations may increase the concentration of free T₄ in serum, we added increasing amounts of oleic acid to pooled normal human serum (with known FFA content) and measured free T₄ by equilibrium dialysis. Total FFA up to 3 meq/liter in normal serum, representing an FFA to albumin molar ratio of about 5:1, had little or no effect on the free T₄ concentration, while higher FFA concentrations progressively increased free T₄. This same molar ratio of FFA to albumin had to be exceeded to cause a significant increase in the free T₄ concentration in diluted serum and in serum from patients with nonthyroid illness. Serum from which more than 95% of the albumin had been removed by chromatography with Affi-Gel blue was much more sensitive to the effects of FFA on free T₄. This enhanced sensitivity was reversed by readdition of albumin to the serum, and the addition of albumin to normal serum resulted in diminished effects of FFA on free (T)₄(.) These results indicate the following: 1) physiological concentrations of FFA do not significantly increase the free T₄ concentration in normal human serum; 2) when FFA reach supraphysiological concentrations in serum (in vitro) and the higher affinity FFA-binding sites on albumin become saturated (apparently at an FFA to albumin molar ratio of 5:1), the excess FFA interact with other serum proteins, including thyroid hormone-binding globulin, and thereby increase the free T₄ concentration; 3) the concentration of albumin (or other FFA binders) must be considered when evaluating the observed effects of FFA.

To explore the relevance of these findings to the hypothesis that FFA may inhibit the binding of T₄ to plasma proteins in patients with nonthyroid illness, we measured plasma FFA concentrations in 11 severely ill patients hospitalized in the intensive care unit. We found a mean plasma FFA concentration of 0.45 ± 0.11 (±SEM) mEq/liter and a mean serum albumin concentration of 2.39 ±0.29 g/dl in these patients. Their mean plasma FFA to albumin molar ratio was 1.53 ± 0.41. Since the FFA to albumin molar ratio must exceed about 5:1 before a significant increase in the serum free T₄concentration occurs, these results suggest tha t FFA do not commonly influence the circulating free T₄ concentration in vivo, even in severely ill patients.

^* This work was supported by the Medical Research Service of the V.A. and Grants HL-14237 (Arteriosclerosis SCOR) and HL-01546 (Clinical Investigator).

Charles E. Culpeper Foundation Fellow

Received July 1, 1986.

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