The kinetics of distribution between plasma and liver of 131-I-labeled L-thyroxine in man: observations of subjects with normal and decreased serum thyroxine-binding globulin.

Cavalieri, Ralph R.; Searle, G. L.

doi:10.1172/jci105409

Cited by 88 publications

(72 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Serum disappearance curves of radioactive thyroid hormones are curvilinear when plotted semilogarithmically, indicating that a multicompartmental system exists for removal of thyroid hormone from serum in man. Moreover, it has been demonstrated previously that a significant portion of thyroid hormones are removed by the liver and the kidney (29). The findings obtained by utilizing single-compartmental kinetics do not provide direct insight into the cellular clearance of thyroid hormones.…”

Section: Resultsmentioning

confidence: 92%

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

View full text Add to dashboard Cite

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.

show abstract

Section: Resultsmentioning

confidence: 92%

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

View full text Add to dashboard Cite

show abstract

“…Assuming a total cellular distribution of space of T3 of 33 liters (= total T3 distribution space of 40 liters [5] -albumin space of 7 liters [19]) the hepatic space of T3 would constitute only 8.3% of the total cellular T3 space. The same authors have estimated that the hepatic distribution space of T4 is 3.8 liters (20). The cellular distribution volume of T4 estimated from the difference of the total distribution volume given by these authors, 12.4 liters, and the protein distribution space of 7 liters is 5.4 liters.…”

Section: Discussionmentioning

confidence: 97%

Differences in primary cellular factors influencing the metabolism and distribution of 3,5,3′-L-triiodothyronine and L-thyroxine

Oppenheimer¹,

Schwartz²,

Shapiro³

et al. 1970

J. Clin. Invest.

View full text Add to dashboard Cite

A B S T R A C T Administration of phenobarbital, which acts exclusively on cellular sites, results in an augmentation of the liver/plasma concentration ratio of L-thyroxine (T4) in rats but no change in the liver/plasma concentration ratio of L-triiodothyronine (T3). Whereas phenobarbital stimulates the fecal clearance rate both of T3 and T4, it increases the deiodinative clearance rate of T4 only. These findings suggest basic differences in the cellular metabolism of T3 and T4. Further evidence pointing to cellular differences was obtained from a comparison of the distribution and metabolism of these hormones with appropriate corrections for the effect of differential plasma binding. The percentage of total exchangeable cellular T4 within the liver (28.5) is significantly greater than the corresponding percentage of exchangeable cellular T3 within this organ (12.3). Extrahepatic tissues bind T3 twice as firmly as T4. The cellular metabolic clearance rate (= free hormone clearance rate) of T3 exceeds that of T4 by a factor 1.8 in the rat. The corresponding ratio in man, 2.4, was determined by noncompartmental analysis of turnover studies in four individuals after the simultaneous injection of T4-'I and T3-2"I. The greater cellular metabolic clearance rate of T3 both in rat and man may be related to the higher specific hormonal potency of this iodothyronine.

show abstract

“…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%

Albumin synthesis in cirrhotic subjects with ascites studied with carbonate-14C

Rothschild¹,

Oratz²,

Zimmon³

et al. 1969

J. Clin. Invest.

139

View full text Add to dashboard Cite

The kinetics of distribution between plasma and liver of 131-I-labeled L-thyroxine in man: observations of subjects with normal and decreased serum thyroxine-binding globulin.

Cited by 88 publications

References 30 publications

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

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

Differences in primary cellular factors influencing the metabolism and distribution of 3,5,3′-L-triiodothyronine and L-thyroxine

Albumin synthesis in cirrhotic subjects with ascites studied with carbonate-14C

Contact Info

Product

Resources

About