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Influence of Fasting and Refeeding on 3,3',5'-Triiodothyronine Metabolism in Man^*

Department of Medicine, University of Southern California Medical School Los Angeles, California 90033

Address requests for reprints to: Jonathan S. LoPresti, M.D., Ph.D., University of Southern California School of Medicine, 2025 Zonal Avenue, Room 18415, Los Angeles, California 90033.

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 an iv dose of 25 µCi [¹²⁵I]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.

^* This work was supported in part by NIH Grant AM-11727 and General Clinical Research Center Grant MO1-RR-43.

Received May 4, 1990.

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