3,3′-Diiodothyronine Production, a Major Pathway of Peripheral Iodothyronine Metabolism in Man

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Abstract

3,3′-Diiodothyronine (3,3′-T2) has been detected in human serum and in thyroglobulin. However, no quantitative assessment of its clearance rate (CR), production rate (PR), or of the importance of extrathyroidal sources of 3,3′-T2 relative to direct thyroidal secretion is yet available. This study examines these parameters in seven euthyroid subjects, and in eight athyreotic subjects (H) eumetabolic due to thyroxine therapy (HT4) (n = 5) or triiodothyronine replacement (HT3) (n = 3). A highly specific radioimmunoassay for the measurement of 3,3′-T2 in whole serum was developed. Serum 3,3′-T2 concentrations were (mean ± SD) 6.0±1.0 ng/100 ml in 13 normal subjects, 9.0±4.6 ng/100 ml in 25 hyperthyroid patients, and 2.7±1.1 ng/100 ml in 17 hypothyroid patients. The values in each of the latter two groups were significantly different from normal. 3,3′-T2 was detected regularly in normal concentrations in 11 hypothyroid patients eumetabolic by treatment with synthetic T4, in 10 eumetabolic patients suffering from nonthyroidal systemic illness, and in 2 subjects with elevated serum T4-binding globulin. The 3,3′-T2 CR was assessed from data acquired from the 125I-3,3′-T2 constant infusion technique. The 3,3′-T2 PR was calculated from CR and serum concentration of 3,3′-T2 determined by radio-immunoassay. In the HT4 subjects the 3,3′-T2 CR averaged 840±377 liters/day and 3,3′-T2 PR 33.9±12.5 μg/day. These results were not significantly different from those in the control group: 3,3′-T2 CR 628±218 liters/day and 3,3′-T2 PR 39.8±19.8 μg/day (all corrected to 70 kg body wt). In addition to 3,3′-T2 PR, T3, and reverse triiodothyronine (rT3) PR were determined in three of the HT4 subjects. In each case studied, the 3,3′-T2 PR was close to the combined triiodothyronine (T3 + rT3) PR. The mean molar ratio of T2 PR/(T3 + rT3) PR was 1.08±0.10. The results obtained in the HT4 subjects indicate that the production of 3,3′-T2 is a major route of T4 metabolism. The combined studies of 3,3′-T2, T3 and rT3 PR in the HT4 subjects indicate that both T3 and rT3 are major precursors of 3,3′-T2. In the HT3 subjects, the conversion of T3 to 3,3′-T2, determined as the molar ratio of 3,3′-T2 PR to T3 PR, ranged from 0.36 to 0.92, providing further evidence that T3 is a precursor of 3,3′-T2. From the close agreement between the mean values for 3,3′-T2 PR in the euthyroid and HT4 group it is concluded that most, if not all of the 3,3′-T2 produced in normal humans is derived by extrathyroidal conversion from T3 and rT3.

Authors

Laurence A. Gavin, Margaret E. Hammond, James N. Castle, Ralph R. Cavalieri