Simultaneous Measurement of Thyroxine and Triiodothyronine Peripheral Turnover Kinetics in Man

Nicoloff, John T.; Low, James C.; Dussault, Jean H.; Fisher, Delbert A.

doi:10.1172/jci106835

Cited by 216 publications

(103 citation statements)

References 28 publications

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“…Thus, the significance of the contribution of the peripheral metabolism of T4 to PR-T3 has been evaluated in several studies using different methods (5,15,20,26,27), and in each case it has been estimated that peripheral conversion of T4 to T3 may contribute about 22-24 ig of Ts. Since recent studies using Ts radioimmunoassay indicate that daily euthyroid PR-Ts may only be about 28-36 'g/day (6,28) the results of the present study agree with the previous studies in indicating that peripheral metabolism of T4 must normally be a major source of T3; studies in sheep have also led to a similar conclusion (29).…”

Section: Discussionsupporting

confidence: 91%

“…While considerable data are available in case of T3 (3)(4)(5)(6), there is a paucity of information about the kinetics of peripheral metabolism and the daily 'Abbresiations used in this paper: MCR(s), metabolic clearance rate(s); PR(s), production rate(s); reverse T8, rT3, 3,3',5'-triiodothyronine; T2, 3,3'-L-diiodothyronine; T3, 3,5,3'-triiodothyronine; T4, thyroxine; TCA, trichloroacetic acid.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

An assessment of daily production and significance of thyroidal secretion of 3, 3', 5'-triiodothyronine (reverse T3) in man.

Chopra¹

1976

J. Clin. Invest.

302

111

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A B S T R A C T While 3,3',5'-triiodothyronine (reverse TS, rTs) has been detected both in human serum and in thyroglobulin, no quantitative assessment of its metabolic clearance rate (MCR), production rate (PR), or secretion by the thyroid is yet available. This study examines this information in euthyroid subjects and evaluates it in light of similar information about two other iodothyronines in the thyroid: 3,5,3'-triiodothyronine (Ta) and thyroxine (T4). Thus, it was noted that rTs is cleared from human serum at a much faster rate than are Ts and T4; the mean (±-SE) MCR of rT3 was 76.7±5.4 liters/day in 10 subjects, whereas MCR-T3 and MCR-T4 in 8 of them were 26.0±2.2 liters/day and 1.02±0.06 liters/day, respectively. Therefore, even though the mean serum concentration of rT3, 48+2.8 ng/ 100 ml, was much lower than that (128±6.7 ng/100 ml) of T3, the mean PR-rTs (36.5+2.8 ,ug/day) and the mean PR-T3 (33.5±3.7 Ag/day) were similar; in comparison, the mean serum concentration and PR of T4 were 8.6± 0.5 ,ug/100 ml and 87.0±3.9 Mg/day, respectively. These data and those on the relative proportion of rT3, T3, and Ts in 10 thyroid glands were used to assess the significance of the contribution of thyroidal secretion to PRrTs and PR-Ta. It was estimated that whereas thyroidal secretion may account for about 23.8% of serum T3 (or PR-Ta), it may account for only about 2.5% of serum rTa (or PR-rTs). Since peripheral metabolism of T4 is the only known source of rT3 and Ta other than the thyroidal secretion, it could be calculated that as much as 73.0 Ag or 84% of daily PR-T4 may normally be metabolized by monodeiodination either to T3 or to rT3.MCR and PR of various iodothyronines were also examined in five cases with hepatic cirrhosis, where, as documented previously, serum rT3 may be elevated while Received for publication 2 September 1975 and in revised form 20 February 1976. serum Ta is diminished. The mean MCR-rT3 in these cases (41.0 liters/day) was clearly (P < 0.005) less than that (76.7 liters/day) in normal subjects. This was the case at a time when the mean MCR-Ta (26.7 liters/day) and the mean MCR-T4 (1.19 liters/day) did not differ from those (vide supra) in normal subjects. Distinct from changes in MCRs, the mean PR-rT3 (33.0 Ag/day) was similar to, and the mean PR-T3 (10.1 ug/day) and the mean PR-T4 (66.4 Mg/day) were much less than, the corresponding value in normal subjects. Furthermore, while the ratio of PR-rT3 and PR-T4 (rT3/T4) in individual patients was either supranormal or normal, the ratio of PR-Ta and PR-T4 (T3/T&) was clearly subnormal. The various data suggest that: (a) just as in the case of T3, the thyroid gland is a relatively minor source of rT3; peripheral metabolism of T4 is apparently its major source; (b) the bulk of T4 metabolized daily is monodeiodinated to T3 or to rT3; (c) monodeiodination may be an obligatory step in metabolism of T4; (d) monodeiodination of T4 to rTa is maintained normal or is increased in hepatic cirrhosis at a time when monodeiodination of T4 to Ta is decr...

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Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

An assessment of daily production and significance of thyroidal secretion of 3, 3', 5'-triiodothyronine (reverse T3) in man.

Chopra¹

1976

J. Clin. Invest.

302

111

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“…The reduced T4 availability in this condition is confirmed by the significant increase (P < 0.001) ofthe initial distribution (or plasma) pool (36.9% of the total pool vs. 28.8% of the controls) and also by the changes in T4 TR from plasma and in T4 FCR, which are reduced by 53% and 32.8%, respectively. A close reduction of T4 FCR in congenital TBG elevation has been reported also by Nicoloff et al (35). The reduction of T4 MCR in FDH subjects was less marked than that found in the increased TBG state, indicating that the T4 carried by abnormal albumin is more available to peripheral tissues than the T4 carried by TBG.…”

Section: Discussionsupporting

confidence: 83%

Role of serum carrier proteins in the peripheral metabolism and tissue distribution of thyroid hormones in familial dysalbuminemic hyperthyroxinemia and congenital elevation of thyroxine-binding globulin.

Bianchi¹,

Iervasi²,

Pilo³

et al. 1987

J. Clin. Invest.

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To investigate the role of thyroxine-binding globulin (TBG) and albumin in the availability of thyroid hormones to peripheral tissues, comprehensive kinetic studies of thyroxine (T4) and triiodothyronine (T3) were carried out in eight subjects with familial dysalbuminemic hyperthyroxinemia (FDH), in four subjects with inherited TBG excess, and in 15 normals. In high-TBG subjects, the reduction of T4 and T3 plasma clearance rates (by 51% and 54%, respectively) was associated with normal daily productions; T4 and T3 distribution volumes were significantly reduced. In FDH subjects T4 clearance was less reduced (by 31%) than in high TBG; consequently T4 production rate was significantly increased (by 42%), T4 and T3 distribution volumes and T3 clearance rate were unchanged. Increased T3 peripheral production in FDH (by 24%) indicates that T4 bound to abnormal albumin is more available to tissues than T4 carried by TBG, thus suggesting an important role of albumin in T4 availability to the periphery.

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“…of 1.21 ± 0.24 1/day and a 98% confidence limit (mean ± 2 S.D.) of 0.73-1.691/day [10,[15][16][17][18].…”

Section: Discussionmentioning

confidence: 99%

Thyroxine (T4) Metabolism in an Athyreotic Patient Who Had Taken a Large Amount of T4 at One Time.

et al. 1998

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Abstract. As we had an opportunity to take blood samples from a totally thyroidectomized patient who had attempted suicide by taking 2,000 tg of Levothyroxine (L-T4), the serum levels of thyroid hormones were sequentially measured to investigate the metabolism of circulating thyroid hormones in an athyreotic human. The serum concentrations of most thyroid hormones reached a peak on the second day, but the serum T3 level showed a peak one day later. The maximum concentrations of T4 (315 µg/l), FT4 (48.8 ng/l) and rT3 (0.80 µg/l) were very high, while the peak T3 level (1.92 jug/l) did not exceed the upper limit of the normal range. The serum T4 and rT3 levels returned to their normal range 13-17 days after the suicide attempt. The TSH level was suppressed rapidly and reached its nadir (0.044 mU/I) on the 6th day. During this period, the T112 and MCR of serum T4 were 10.4 days and 0.64 1/day, respectively, which values were almost equivalent to those observed during 15 days after discontinuation of the maintenance L-T4 therapy. In summary, the oral intake of a large amount of L-T4 at one time does not induce a proportional increase in the T3 level in an athyreotic person. The MCR of serum T4 is decreased and the T112 of serum T4 is prolonged, probably due to the lack of intrathyroidal deiodination. These findings support the conclusion that the D1 activity in the thyroid is one of the major determinants in the metabolic clearance of serum T4. Wenzel et al. [5] reported that the maximum concentration of serum T3 after oral intake of an excessive dose (3000 ,ug) of Levothyroxine (L-T4) at one time did not exceed the upper limit of normal range in normal subjects.Nevertheless, the contribution of the thyroid to systemic T4 metabolism is not clear and the precise consequence has not been well documented in reference to the high T3 level in patients with hyperthyroid Graves' disease. In order to evaluate the effect of the thyroid on the metabolism of circulating thyroid hormones, we examined the metabolism of thyroid hormones in an athyreotic patient who had taken an excessive dose of L-T4 at one time.

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Simultaneous Measurement of Thyroxine and Triiodothyronine Peripheral Turnover Kinetics in Man

Cited by 216 publications

References 28 publications

An assessment of daily production and significance of thyroidal secretion of 3, 3', 5'-triiodothyronine (reverse T3) in man.

An assessment of daily production and significance of thyroidal secretion of 3, 3', 5'-triiodothyronine (reverse T3) in man.

Role of serum carrier proteins in the peripheral metabolism and tissue distribution of thyroid hormones in familial dysalbuminemic hyperthyroxinemia and congenital elevation of thyroxine-binding globulin.

Thyroxine (T4) Metabolism in an Athyreotic Patient Who Had Taken a Large Amount of T4 at One Time.

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