Radiothyroxine Turnover Studies in Thyroid Disease After Therapy

Sterling, Kenneth

doi:10.1172/jci103724

Cited by 31 publications

(11 citation statements)

References 12 publications

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“…Thus, one cannot readily ascribe any of the age-dependent changes in thyroxine turnover to the metabolic effects of other hormones, the levels of which might in turn be agerelated. Thyroxine fractional turnover rate is increased in hyperthyroidism (6,7,13,14), but it is thought to be decreased in myxedema (7,13). Our present observations may have some bearing upon the latter contention.…”

Section: Resultssupporting

confidence: 50%

“…Since a significant number of the studied myxedematous subjects were in an older age group, the decreased turnover may perhaps be attributable, at least in part, to age. A study of thyroxine turnover in myxedematous individuals before and after thyroid replacement therapy, in which treatment resulted in increased fractional turnover in most of the subjects (13), suggests that the hypothyroid state is indeed accompanied by a decrease in thyroxine fractional turnover rate. In view of earlier results (6), however, lack of uniform response to treatment (13), lack of statistical comparison of the paired turnover curves, and the presently demonstrated effect of age on thyroxine turnover, one might yet be cautious in concluding that myxedema results in decreased thyroxine turnover.…”

Section: Resultsmentioning

confidence: 99%

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Thyroxine Turnover in Euthyroid Man With Special Reference to Changes With Age

Gregerman¹,

Gaffney²,

Shock³

1962

J. Clin. Invest.

170

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For many years the thyroid was thought to be involved in the decrease of basal metabolic rate that accompanies advancing age. Although recent evidence suggests that the change in oxygen consumption may merely reflect a decrease in "metabolic mass" (1), the advent of radioisotope techniques and methods for measuring the level of thyroid hormone in blood led to the hope that new information bearing on the role of the thyroid might become available. We have reviewed the investigations of others and presented our own results in previous publications dealing with the relationship of age to serum protein-bound iodine (PBI) and the thyroidal accumulation of radioiodide in euthyroid man (2, 3). The data suggest that the PBI does not change, but that radioiodide accumulation and thyroidal plasma radioiodide clearance decrease with age.Unfortunately, the radioiodide data are difficult to interpret, since it is not possible to equate a decrease in the uptake of tracer radioiodide with a decrease in thyroid hormone formation (3). Moreover, although the statistical significance of the age-dependent decrease in uptake is clear, the scatter of the individual values is such that the magnitude of the change can be only approximated. Although clinically useful for studying the extremes of thyroid function, there is little evidence that the basal metabolic rate, the serum PBI, or the thyroidal uptake of radioiodide is closely related to the rate of thyroid hormone production in euthyroid man. None of the available studies, therefore, particularly clarifies the issue of whether thyroid activity changes with age.About ten years ago Riggs reviewed the methods available for estimating quantitatively the rate of thyroid hormone formation, but these have not been used in studies of the relationship of age to thyroid function (4). A few years later several investigators described the radiothyroxine turnover technique that permits quantitative estimation of thyroid hormone output in man (5, 6, 7). An important advantage of this method is that it also allows independent determinations of the thyroxine distribution space, pool size, and fractional turnover rate. We undertook the present study hoping to define the range of thyroid function in euthyroid man and the relationship of age both to over-all gland activity and these parameters of thyroid hormone utilization. A preliminary report of our results has been presented (8). METHODSIn general the methods used here have been described by Ingbar and Freinkel (6) and by Sterling and Chodos (7). Radioactive thyroxine labeled with I"31 was obtained from the Abbott Co. as a 50 per cent propylene glycol solution containing approximately 500 1uc per ml, with specific activity ranging from 20 to 40 mc per mg. Over the period of this study (from early 1957 to the middle of 1958) many thyroxine preparations were used. The thyroxine was administered within a few days to a week after receipt, although a few determinations were made with material as old as three weeks. Although the labeled material is ma...

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Section: Resultssupporting

confidence: 50%

Section: Resultsmentioning

confidence: 99%

Thyroxine Turnover in Euthyroid Man With Special Reference to Changes With Age

Gregerman¹,

Gaffney²,

Shock³

1962

J. Clin. Invest.

170

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“…Despite the high concentrations of both hormones, one cannot assume markedly elevated removal rates in these patients in the absence of kinetic data. Even after many months of replacement therapy, persistently prolonged biologic half-time of T4 has been observed in myxedema (35). It has generally been assumed that maintenance of a euthyroid state with L-T4 requires doses sufficient to raise the serum T4 concentration well above the normal range, since the metabolic contribution normally afforded by T3 is lacking.…”

Section: Discussionmentioning

confidence: 99%

Conversion of Thyroxine (T4) to triiodothyronine (T3) in athyreotic human subjects

Braverman¹,

Ingbar²,

Sterling³

1970

J. Clin. Invest.

Self Cite

466

167

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A B S T R A C T Studies of the possibility that thyroxine (T4) is converted to 3,5,3'-triiodo-L-thyronine (T3) in the extrathyroidal tissues in man have been conducted in 13 patients, all but two of whom were athyreotic or hypothyroid, and all of whom were receiving at least physiological replacement doses of synthetic sodium-Lthyroxine.T3 was found in the sera of all patients, in concentrations ranging between 243 and 680 ng/100 ml (normal range 170-270 ng/100 ml). These concentrations were far in excess of those which would have been expected on the basis of the T3 contamination of the administered T4, as measured by the same technique employed in the analysis of serum. When oral medication was enriched with 'I-labeled T4 for 8 or more days, labeled T3 and tetraiodothyroacetic acid (Tetrac or TA4) were found in the serum to the extent of approximately 2-5% of total radioactivity, as assessed by unidimensional paper chromatography. The same results were obtained with a specially purified lot of radioactive T4 containing less than 0.1% T3 as a contaminant. The identities of the 'I-labeled T3 and TA4 were verified by two-dimensional chromatography as well as by specific patterns of binding in serum. The labeled T3 isolated was bound by albumin and by T4-binding globulin (TBG), but not by T4-binding prealbumin (TBPA); in contrast the labeled TA4 was bound by albumin and TBPA, but not by TBG.To exclude the possibility that the conversion of T4 to T3 was a peculiarity of the oral route of administra- There is no doubt whatsoever that at least a portion of the T3 in the blood results from direct secretion by the thyroid gland, T3 having been found in the thyroid venous effluent, and in concentrations substantially higher than in the concurrently sampled arterial blood (4, 5). What has remained uncertain, however, is what fraction, if any, of the T3 in the blood arises from the

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“…In thyroid disease the deviations from the normal range in the calculated absolute values for free thyroxine iodine were quite pronounced and could conceivably explain the differences in removal rate reported several years ago (21,22). In the discussions of these papers at that time, the variations from normal were considered primarily in relation to possible differences in tissue metabolism, although mention was made of possible differences in serum protein binding.…”

Section: Discussionmentioning

confidence: 99%