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Serum Concentration, Metabolic Clearance, and Production Rates of 3,5,3'Triiodothyroacetic Acid in Normal and Athyreotic Man^*

Division of Endocrinology-Metabolism and the Nuclear Medicine Service, Veterans Administration Medical Center, and the Department of Medicine, University of California San Francisco, San Francisco, California 94121

Address requests for reprints to: Dr. Laurence A. Gavin, Division of Endocrinology-Metabolism, Veterans Administration Medical Center (115), 4150 Clement Street, San Francisco, California 94121.

It has been demonstrated that 3,5,3'-triiodothyroacetic acid (Triac) is present in normal human serum. However, no quantitative assessment of its clearance rate (CR), production rate (PR), or the importance of extrathyroidal sources of Triac relative to direct thyroidal secretion is yet available. These parameters are here reported in five euthyroid subjects and eight athyreotic subjects (H) eumetabolic on T4 therapy (HT₄; n = 5) or T₃ (HT₃; n = 3). The Triac concentration was determined by RIA in serum extracts. Each sample was corrected for recovery. The mean serum Triac concentration was 2.6 ± 0.2 ng/100 ml (mean ± SE) in 26 normal subjects. Triac was also detectable in serum from the HT₄ and HT₃ subjects (2.3 ± 0.2 and 3.8 ± 0.2 ng/100 ml, respectively). The latter value was significantly (P < 0.01) higher than the control mean. The Triac CR was determined from data acquired using an [¹²⁵I]Triac constant infusion technique. Samples were analyzed by both anion exchange and Sephadex G-25F column chromatography. The serum concentrations of [¹²⁵I]Triac were similar by both methods of analysis. In the control subjects, the Triac CR averaged 222 ± 37 liters/day, whereas the means were 198 ± 31 and 268 ± 4 liters/day in the HT₄ and HT₃ group, respectively. The Triac PR was calculated from the CR and serum concentration of Triac. The control mean PR at 5.2 ± 1.5 µg/day was similar to the HT₄ mean of 4.4 ± 0.5 jug/day (all corrected to 70 kg BW). The mean Triac PR was significantly higher (P µ 0.025) in the HT₃ group (10.1 ± 0.4 µg/day) compared to the control average. The mean molar ratio of the Triac PR to the daily T₃ dose in the HT₃ group was 0.14 ± 0.02. The similar Triac PR values in the controls and the HT₄ group indicate that Triac is generated mainly from the extrathyroidal metabolism of T₄ and that direct thyroidal secretion contributes little if at all to its daily production. The studies in the HT₃ group indicate that alteration of the alanine side chain is an important pathway (14% of T₃ degradation) in T₃ degradation and that T₃ is the major precursor of Triac in vivo.

^* Presented in part at the 61st Annual Meeting of The Endocrine Society, Anaheim, CA, June 1979, and published in abstract form [Endocrine Society Program and Abstracts 61: 91, 1979 (Abstract 76)]. This work was supported by the V.A. and Grant AM-24012-01 from the NIH.

Received January 17, 1980.

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