Alterations in hepatocyte uptake and plasma binding of thyroxine in nonthyroidal illness and caloric deprivation.
Low plasma T(3) in severe illness is widely thought to be due principally to inhibition of 5'-deiodinase activity, but other factors also contribute to this response. Abnormal plasma constituents, namely, 3-carboxy-4-methyl-5-propyl-2-furan propanoic acid (CMPF) and indoxyl sulfate in uremia, and elevated bilirubin and nonesterified fatty acids (NEFA) can impair T(4) transport into hepatocytes, thereby contributing to the lowering of plasma T(3). Assessment of possible endogenous or exogenous inhibitors of T(4) binding to plasma proteins is prone to dilution-dependent artifacts, which can lead to overestimation or underestimation of competitor potency, depending on experimental details. Because the potency of such competitors is a function of their free concentrations in undiluted serum, inhibitory activity may be enhanced by substances that impair their albumin binding. Oleic acid or CMPF can inhibit the effect of drugs such as furosemide or fenclofenac.
Lim
C F
CF
Ewen Downie Metabolic Unit, and Monash University Department of Medicine, Alfred Hospital, Melbourne, Victoria, Australia, 3181.
Stockigt
J R
JR
Hennemann
G
G