Fatty acid induced changes in circulating total and free thyroid hormones: in vivo effects and methodological artefacts.

Elevated levels of nonesterified fatty acids (NEFA) are frequently found in acute illnesses, and they may contribute to changes in serum thyroid hormone concentrations in nonthyroidal illnesses (NTI) by displacing protein bound hormones. We therefore examined the effects of low and raised plasma NEFA levels on circulating total and free thyroxine (TT4 and FT4) and triiodothyronine (TT3 and FT3) concentrations, the Free T4 Index (FT4I) and TSH, in a randomized crossover study in 10 normal subjects. Subjects ate either a high carbohydrate breakfast (low NEFA protocol) or a high fat breakfast followed by an iv injection of 1000 u heparin (high NEFA protocol). Possible biological effects of changes in FT4 and FT3 were evaluated by a 200 micrograms iv TRH test. Free T4 and T3 were measured by a direct analogue method (AFT4 and AFT3). In a similar high NEFA study, but without TRH, FT4 was also measured by equilibrium dialysis (DFT4) and a 2-step RIA method (2-step FT4). Acute elevations of plasma NEFA from 0.67 +/- 0.08 mmol/L to a peak of 2.6 +/- 0.54 mmol/L resulted in a prompt reciprocal fall of mean TT4 (-8.7%, p less than 0.01), AFT4 (-30%, p less than 0.005) and TT3 (-11.5%, p less than 0.01) and AFT3 (-16%, p less than 0.005); DFT4 rose significantly from 23.7 +/- 1.9 pmol/L to 33.0 +/- 3.7 pmol/L (+39%, p less than 0.025) and 2-step FT4 rose by 16% (p less than 0.05). TSH levels declined consistently from 3.3 +/- 0.5 mIU/L to 2.6 +/- 0.4 mIU/L (p less than 0.025).(ABSTRACT TRUNCATED AT 250 WORDS)