A new method for measuring the free thyroid hormone in human serum and an analysis of the factors that influence its concentration.

Ingbar, Sidney H.; Braverman, Lewis E.; Dawber, Nancy A.; Lee, Glenn Y.

doi:10.1172/jci105275

Cited by 173 publications

(80 citation statements)

References 34 publications

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“…We determined that T4 was bound to plasma proteins about 10 times as avidily as T3 both in man and the rat. This finding agrees with previous estimates (21,22 is a larger cellular clearance rate of T3, a finding which is related to the fractional removal rates from the cellular pools of T3 and T4 (kc) which can be calculated to be about 0.7 and 0.2 (day-') respectively. The difference in the cellular metabolic clearance rates in man is therefore determined by the fractional removal of the intracellular hormones whereas in the rat, the difference in cellular metabolic clearance rates is determined by cellular binding of T3 and T4.…”

Section: Discussionsupporting

confidence: 92%

“…Since it is difficult experimentally to determine the proportion of cellular binding sites which are metabolically linked it is more convenient for most purposes simply to determine the cellular metabolic clearance rate, Bck., which is numerically equal to the free hormone clearance rate, a concept previously used by Ingbar, Braverman, Dawber, Lee (21). Determination of total cellular binding, however, can be useful under certain circumstances in obtaining indications about the precise tissue or organ in which metabolic changes occur.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

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.

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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.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

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.

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“…The percentage and absolute concentrations of free T4 in the serum of patients with normal and molar pregnancy are also shown in Table III. In accord with earlier observations, the percentage of free T4 in serum was significantly decreased during normal pregnancy (9,20). The absolute concentration of free T4 in serum, however, was only slightly, and not significantly, lower than normal.…”

Section: Indices Of Thyroid Functionsupporting

confidence: 91%

“…In such cases, it would be expected that the proportion of free T4 would be substantially increased, and it seems anomalous that such was not the case; values in such cases being increased only moderately, if at all. Previous studies have suggested, however, that the extent of increase in the proportion of free T4 that occurs when binding sites on TBG are saturated depends upon the availability of binding sites on TBPA (9,30,31 With few exceptions (15,(32)(33)(34), previously reported cases of trophoblastic tumor which demonstrated thyroid hyperfunction or marked increases in serum PBI were peculiar in that they failed to display signs or symptoms of frank thyrotoxicosis. A similar paradox was evident in the present series of patients, who appeared clinically euthyroid and yet presented multiple lines of evidence suggesting hypersecretion of T4.…”

Section: Thyroid Hormone Economy In Molar Pregnancymentioning

confidence: 99%

Alterations in thyroid hormone economy in patients with hydatidiform mole

Galton¹,

Ingbar²,

Jimenez-Fonseca³

et al. 1971

J. Clin. Invest.

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A B S T R A C T Studies of several aspects of thyroid hormone economy have been conducted in 11 patients before and after removal of a molar pregnancy. Before evacuation of the mole, all patients demonstrated moderately to greatly elevated values for thyroidal 'I uptake, absolute iodine uptake, and serum protein-bound-I. Values for serum PBI and serum thyroxine (T4) concentration were consistently and often greatly increased, averaging more than twice those found in normal pregnancy and three times those in normal controls. On the other hand, the maximum binding capacity of the T4-binding globulin (TBG) was variably affected, and ranged between the values found in normal controls and those found in normal pregnancy. Values for the absolute concentration of free T4 in serum were, on the average, only moderately elevated, since the proportion of free To was moderately low, although not as low as in normal pregnancy. Sera of patients with molar pregnancy contained high levels of thyroid stimulating activity, as assessed in the McKenzie mouse bioassay system. The stimulator displayed a more prolonged duration of action than that of TSH and did not reveal a major immunological cross-reactivity with either human or bovine TSH, differing in the latter respect from the chorionic thyrotropin of normal human placenta. Abnormalities in iodine metabolism were rapidly ameliorated after removal of the molar pregnancy, and this was Despite the foregoing evidence of thyroid hyperfunction and hypersecretion of T4, patients with molar pregnancy were neither goitrous nor overtly thyrotoxic. They did display, however, high values of the urinary pigment/creatinine ratio, a possible indication of the presence of a hypermetabolic state.It is concluded that in patients with molar pregnancy, thyroid function and T4 secretion are stimulated, often greatly so, by an unusual thyroid stimulator which is demonstrable in the blood and which is probably of molar origin. The nature of the stimulator, as well as the reasons for both the variability of the increase in TBG which occurs in molar pregnancy and the lack of frank thyrotoxicosis, remain to be clarified.

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“…Interrelationships among serum free thyroxine (T 4 ), 3 the proteins that bind T 4 , protein-bound T 4 , and total T 4 are variable (1)(2)(3)(4)(5)(6). Protein-bound and total T 4 concentrations vary (correlate) directly with free T 4 concentrations when serum T 4 -binding proteins are constant.…”

mentioning

confidence: 99%

A Direct Free Thyroxine (T4) Immunoassay with the Characteristics of a Total T4 Immunoassay

Fritz¹,

Wilcox²,

Nelson

2007

Clinical Chemistry

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Background: Direct free thyroxine (T 4 ) measurements have been linked to both T 4 -binding serum protein concentrations and protein-bound T 4 concentrations. Whether this is evidence of a relationship to total T 4 concentrations has not been reported. Methods:We compared an analog-based direct free T 4 immunoassay and a total T 4 immunoassay. Each assay was applied to the fractions of serum T 4 obtained by ultrafiltration and equilibrium dialysis. Both were applied to serum-based solutions in which free T 4 , T 4 -binding proteins, protein-bound T 4 , and total T 4 were systematically varied, held constant, or excluded. Results: Neither the free T 4 assay nor the total T 4 assay detected dialyzable or ultrafilterable serum T 4 . Both assays detected and reported the T 4 retained with serum proteins. Both free and total T 4 results were related to the same total T 4 concentrations in the presence and absence of T 4 -binding proteins. Both results were similarly related to total T 4 concentrations when free T 4 was held constant while total T 4 was varied. Both were similarly related to a total T 4 concentration that was held constant while free T 4 progressively replaced proteinbound T 4 . These free T 4 results, like total T 4 results, were unresponsive to a 500-fold variation in dialyzable T 4 concentrations. Conclusion: New experiments extend the characterization of a longstanding and incompletely characterized analog-based free T 4 immunoassay. These free T 4 measurements relate to total T 4 concentrations in the same way that total T 4 measurements do.

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A new method for measuring the free thyroid hormone in human serum and an analysis of the factors that influence its concentration.

Cited by 173 publications

References 34 publications

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

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

Alterations in thyroid hormone economy in patients with hydatidiform mole

A Direct Free Thyroxine (T4) Immunoassay with the Characteristics of a Total T4 Immunoassay

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