Endemic Goiter in Greece: Thyroid Hormone Kinetics

Koutras, Demetrios A.; Berman, Mones; Sfontouris, J.; Rigopoulos, G. A.; Koukoulommati, A. S.; Malamos, B.

doi:10.1210/jcem-30-4-479

Cited by 17 publications

(20 citation statements)

References 1 publication

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“…However, our estimate of the clearance rate of Ts, based on the threecompartment model, was still lower than the value obtained by Koutras and his co-workers (33). In contrast, the MCR and total distribution volume of T4 obtained by the extrapolation method agreed closely with those obtained by the three-compartmental analysis in all subjects studied in the present paper.…”

Section: 'supporting

confidence: 68%

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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Section: 'supporting

confidence: 68%

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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“…1) provides for secretion of hormonal and nonhormonal I from several compartments (12)(13)(14), but we did not find it necessary to introduce different lithium effects for each compartment (see legend to Fig. 1).…”

Section: Methodsmentioning

confidence: 89%

“…The kinetic data were analyzed using a general model of iodine metabolism ( Fig. 1) modified from Berman et al (12)(13)(14) and the digital computer program SAAM/25, the latest of the SAAM series (15). Beginning with a set of initial estimates for the rate constants L,,j (designated X,,j in previous papers [12,14]), the computer iteratively adjusted their values until a least squares fit of all the data for a particular study was obtained.…”

Section: Methodsmentioning

confidence: 99%

The Use of Lithium in the Treatment of Thyrotoxicosis

Temple¹,

Berman²,

Robbins³

et al. 1972

J. Clin. Invest.

Self Cite

128

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A B S T R A C T Since lithium has been showx%n to inhibit release of iodine from the thyroid, we have investigated its therapeutic potential in thvrotoxicosis. Eight detailed "lI kinetic studies were performed on seven thvrotoxic women and data was analy,zed using a computer program. Lithium at serum levels of about 1 mEq 'liter decreased the loss of '31I from the thyroid, led to a fall in serum "II levels and diminished urinary "'I excretion. Coinputer simulation of the lithium effect required, in every case, that lithium inhibit hormonal and( nonllormonal thyroid iodine release. In five cases a second lithium effect was required for a satisfactory fit of the model soluton with observed data: namely, an inhibition of hormone disappearance from serunm.Neither inhibition of release nor of hormone disappearance seemled to be affected by mlethimazole (release: 52% decrease without methimilazole, 60,% \w-ith mlethimazole; hormone disappearance: -60% decrease in both). Wlheni Li' was discontinued, recovery of the iodine release rate and hormiione disappearance rate over the observed time span -was variable, ranging from no recovery to rates that exceeded pre-Li' values. When Li' is used alone its effect on serum hormone levels is diminished due to continued accumulation of iodide by the thyroid. Thus, serum thyroxine-iodine levels fell 21-30% in 6-8 days in patients wlho did not receive methimazole and 15-67%C in the methimazoletreated subjects. For prolonged therapy, therefore, a thiocarbamide drug must be used in conjunction witlh Li'. The similarity of inhibition of iodine release from the thvroid produced by Li' and iodides is discussed.

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“…Either the failure to appreciate (4), or adequately compensate for (5), the presence of iodoproteins formed from Ts degradation may have been responsible for these differences. With the exception of the limited data reported by Surks and Oppenheimer (6), it is evident that all previously reported labeled Ts disappearance curves, whether in serum (2)(3)(4)(5)(13)(14)(15) or in the whole body studies (16), suffer from the same technical problem of failure to eliminate the influence of iodoproteins.…”

Section: Discussionmentioning

confidence: 96%

“…This error can be compensated for by using a two compartmental model (9). An apparent 20% overestimation of Ts DS would result in normal subjects if a single rather than a two compartmental model system were used (15).…”

Section: Discussionmentioning

confidence: 99%