Feedback Effectiveness of Periodic Versus Constant Triiodothyronine Replacement*

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Abstract
We have studied some temporal aspects of the feedback inhibition of TSH secretion in unanesthetized rats using two patterns of T3 administration. Rats were thyroidectomized and prepared with chronic jugular catheters through which sequential blood samples were obtained and TRH was administered. Physiological amounts of T3 replacement (280–566 ng/100 g-day) were delivered to the rats by one of two methods: 1) continuous sc infusion by use of the Alzet osmotic minipump or 2) twice daily (800 and 2000 h) sc injections. In rats receiving 280 or 350 ng T3/100 g-day by constant infusion, plasma T3 concentrations were maintained at near-normal levels (50–60 ng T3/dl), but plasma TSH levels rose progressively. The plasma TSH concentration was significantly (P < 0.05) elevated above prethyroidectomy levels as early as 48 h post thyroidectomy and continued to rise throughout 144 h. Constant infusion of 566 ng T3/100 g-day resulted in plasma T3 levels above normal and the maintenance of normal plasma TSH. Rats receiving 322 ng T3/ 100 g-day by twice daily injections displayed the expected periodic fluctuations in plasma T3 concentrations over the 12-h period between injections. At 2 h post injection, the plasma T3 concentration was approximately 100 ng/dl and fell to less than 25 ng/dl at 12 h. Plasma TSH concentrations, however, were significantly suppressed (P < 0.01) compared to prethyroidectomy levels throughout the experiment. In addition, pituitary responsiveness to TRH (250 ng/100 g) was significantly less (P < 0.01) in rats receiving 322 ng T3/100 g-day by injections than in rats receiving 350 ng T3/100 g-day by continuous infusion. These results indicate that physiological amounts of T3 given in twice daily injections are more effective than equal amounts of T3 administered by constant infusion in suppressing TSH secretion in response to thyroidectomy or TRH stimulation. (Endocrinology106: 911, 1980)

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