Thyroxine Turnover and Transport in Laennec's Cirrhosis of the Liver*

Inada, Mitsuo; Sterling, Kenneth

doi:10.1172/jci105620

Cited by 63 publications

(22 citation statements)

References 18 publications

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“…Similar situation has also been observed in normal fetus in whom serum T3 is less than, and serum rT3 is much higher than the adult levels (8). These observations suggest the possibility that alterations in monodeiodination of T4 observed in hepatic cirrhosis and the fetus may also be the explanation in other situations where serum T3 is low and rTs is high (9,36,38).…”

Section: Discussionsupporting

confidence: 76%

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: 76%

“…The Journal of Clinical Investigation Volume 58 July 1976- [32][33][34][35][36][37][38][39][40] turnover rate of reverse T3. Similarly, little information is available regarding the relative significance of the contribution of the thyroidal secretion and the peripheral metabolism of T4 to serum rTa in man.…”

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 MCR obtained by the three-compartme and the T4 production rate were 1.04+0.1 per 60 kg body wt and 83±20 Ag/day per 60 in normal subjects, respectively (Table II) most the same as those of normal subject, reported (8)(9)(10)(11)(12). The patients with untreat roidism had diminished clearance rates of 1 T4 production rates were also markedly diminished (Table II).…”

Section: Resultsmentioning

confidence: 69%

“…Semilogarithmic plots were made of the disappearance curves of radioactive thyroid hormones in serum. The final slope was taken as the fractional turnover rate, the time-zero intercept of this slope was used to estimate the total distribution volume, and the products of the fractional turnover rate and the total distribution volume were the metabolic clearance rates of thyroid hormones (MCR) (8)(9)(10)(11)(12).…”

Section: Methods Of Analysismentioning

confidence: 99%

Estimation of thyroxine and triiodothyronine distribution and of the conversion rate of thyroxine to triiodothyronine in man.

Inada¹,

Kasagi²,

Kurata³

et al. 1975

J. Clin. Invest.

120

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A B S T R A C T Studies on peripheral metabolism of simultaneously administered 125I-labeled L-thyroxine (['I1]T4) and "1'I-labeled L-triiodothyronine ([.1.I]T3) were performed in five normal subjects, in four patients with untreated hypothyroidism, and in 3 hypothyroid patients made euthyroid by the administration of T4. The fractional turnover rate (Xos) of thyroid hormones irreversibly leaving the site of degradation and the volumes of pool 1 (serum, Vi), of pool 2 (interstitial fluid, V2), and of pool 3 (all tissues, V3) were obtained by using a three-compartment analysis. In addition to the turnover studies, the ratios for the in vivo To to T3 conversion were determined by paper chromatographic study in sera obtained 4, 7, and 10 days after the injection. The rate (K12) of the extrathyroidal conversion of T4 to T3 was also estimated by the compartment analysis. The T3 distribution volume (V3) of pool 3, in which T3 is utilized and degraded, was about 60% of total distribution volume (V = V1 + V2+ V3) in normal subjects, whereas only about 25% of the extrathyroidal T4 pool was in the intracellular compartment, indicating that T3 is predominantly an intracellular hormone. The V3/V ratios of T3 were almost constant in a normal ratio of about 60% in hypothyroid patients before and after treatment. On the other hand, the V3/V ratios of T4 were elevated in patients with untreated hypothyroidism, and they returned almost to the normal range after administration of T4. Thus, the V3/V ratio of T4 bore a significant inverse relation to the free T4 concentration in all subjects (r = -0.68, P < 0.05). The findings suggested a redistribution of T4 into the cellular compartment in patients with untreated hypothyroidism. In normal subjects values for K12 averaged 3.00±0.68% per day of the extrathyroidal T4 pool, and the amount of T3 generated by the conversion of T4 (mean-SD, 17±5 Mg/day) was found to contribute approximately 70% of the daily T3 production (mean +SD, 24±5 /Lg/day). The patients with untreated hypothyroidism had elevated Ku2 (mean+SD, 4.16+0.72% per day). Because of diminution of extrathyroidal T4 pool, the amount of T3 converted from T4 was markedly diminished in the untreated patients (mean+SD, 4+3 jug/day), and it agreed closely with T3 production rate (mean±+SD, 3±2 Mg/day). In the patients treated with T4 K,2 returned almost to the normal range (mean±SD, 2.59+0.47% per day), and the amount of T3 arising from deiodination of T4 (mean±+SD, 24±6 Mg/day) corresponded closely to T3 production rate (mean+SD, 21±5 jug/day). Furthermore, a highly significant correlation was evident in the plots of serum T3 concentrations against the amounts of T3 generated by the conversion of T4 in all subjects (r = + 0.85, P < 0.001). The results indicated that the amount of T3 formed by the extrathyroidal conversion of T4 is a major determinant of serum T3 concentration in normal subjects and in patients with hypothyroidism before and after treatment.

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“…Change in colloid osmotic pressure, pressure alterations within the liver, thyroid and cortisone metabolism, as well as changes in the nutritional state, all could influence albumin synthesis (29,32,33,(38)(39)(40)(41)(42)(43)(44).…”

Section: Discussionmentioning

confidence: 99%