INFLUENCE OF FASTING AND REFEEDING ON 3,3',5'-TRIIODOTHYRONINE METABOLISM IN MAN

To determine the influence of prolonged fasting and refeeding on rT3 metabolism in man, five euthyroid obese subjects underwent a 13-day fast, followed by a refeeding period. Each patient received on iv dose of 15-mu-ci [I-125]rT3 during the fed control period, on days 7 and 13 of the fast, and on the fourth day after refeeding with a regular diet. Serial blood and urine samples were obtained to determine serum rT3 clearance and production rates and the urinary tracer rT3 deiodination fraction. Significant increases in serum rT3 values were noted by day 7 and remained elevated for the duration of the fast (P < 0.01). Normalization of rT3 levels occurred after 4 days of refeeding. Both 7 and 13 days of fasting decreased rT3 clearance [132.6 +/- 8.3 L/day (P < 0.001) and 132.2 +/- 9.5 L/day (P < 0.001), respectively] without changing rT3 production (36.8 +/- 5.3 and 33.0 +/- 3.7 nmol/D, respectively) compared to control values (207.0 +/- 10.9 L/day and 31.8 +/- 3.8 nmol/day, respectively). Refeeding did not restore rT3 clearance (151.2 +/- 6.9 L/day; P < 0.002), but significantly reduced blood rT3 production (18.4 +/- 3.8 nmol/day; P < 0.003). The fractional deiodination of rT3 was significantly reduced on day 7 (42.5 +/- 4.6%; P < 0.01) and day 13 (41.9 +/- 3.7%; P < 0.01) of fasting compared to the control value (69.2 +/- 2.8%), while refeeding only partially restored deiodination to baseline (48.4 +/- 5.1%; P < 0.04). The clearance of rT3 was highly dependent on the fractional deiodination rate (r = 0.83%; P < 0.001). Although rT3 production remained constant during fasting, reduced rT3 production was seen on the fourth day of refeeding. This unique observation explained the fall in serum rT3 to prefasting levels after 4 days of refeeding when rT3 clearance was still inhibited. This study, in context with previous investigations, indicates that T4 conversion to circulating T3 and rT3 in fasting is a highly complex and multifaceted process requiring further investigation to elucidate the mechanism responsible for these alterations.