Relationship Between Total Thyroxine and Absolute Free Thyroxine and the Influence of Absolute Free Thyroxine on Thyroxine Disposal in Humans<sup>1</sup>

Hennemann, G; Docter, R.; Dolman, A.

doi:10.1210/jcem-33-1-63

Cited by 25 publications

(5 citation statements)

References 15 publications

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“…In all, the PFT4 was increased. Values for the AFT4I fell at the lower end of the normal range in all four patients, a finding similar to that reported by Hennemann, Beckers, Docter, Dolman, and De Nayer (19). A pronounced increase in total Tc-clearance rate was also observed, values ranging between 2.5 and five times those expected on the basis of age and weight.…”

Section: Discussionsupporting

confidence: 89%

Effects of Norethandrolone on the Transport and Peripheral Metabolism of Thyroxine in Patients Lacking Thyroxine-Binding Globulin

Braverman¹,

AvRuskin²,

Cullen³

et al. 1971

J. Clin. Invest.

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A B S T R A C T Studies of the effect of norethandrolone on the transport and peripheral metabolism of thyroxine were carried out in four patients lacking thyroxine-binding globulin. Before norethandrolone administration, values for serum protein-bound iodine (PBI) were decreased (1.8 ±0.5 Ag/100 ml) and the proportion of free thyroxine increased (0.036 ±0.008%). As a result, values for the absolute concentration of free thyroxine iodine were at the lower end of the normal range (0.63 +0.12 mjug/100 ml). During the control thyroxineturnover study, the thyroxine distribution space was strikingly increased (18.2 ±7.9 liters) and the fractional rate of thyroxine turnover moderately increased (17.1 ±11.3%/day), as compared to the expected mean values for normal subjects. Therefore, calculated values for the daily rate of thyroxine clearance were increased even more, ranging between 255 and 500% of normal values. However, owing to the low PBI in these patients, the daily disposal of thyroxine iodine was similar to that expected in normals on the basis of age and weight. During the administration of norethandrolone, the thyroxine-binding capacity of the thyroxine-binding prealbumin increased strikingly in all patients, values averaging 162% of those found during the control period. This increase was associated with a highly significant increase in PBI (133% of control values) and a small but significant decrease in the proportion of free thyroxine, resulting in no significant change in the abReceived for publication 21 January 1971 and in revised form 3 March 1971. solute concentration of free thyroxine iodine. In all four patients, administration of norethandrolone was associated with a pronounced decrease in the thyroxine distribution space to values which averaged 69% of those found during the control period. Values for the fractional rate of thyroxine turnover increased slightly. As a result, thyroxine-clearance rate decreased in all patients. Owing to the reciprocal changes in clearance rate and PBJ, no significant change in total daily thyroxine disposal was observed. The present studies reveal that when the thyroxine-binding prealbumin is increased in patients lacking thyroxine-binding globulin, several indices of peripheral thyroxine transport and metabolism are altered. However, these changes were small, even in the absence of thyroxine-binding globulin. It is suggested, therefore, that the effect of changes in thyroxine-binding prealbumin would be even smaller in individuals in whom thyroxine-binding globulin is present.

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Section: Discussionsupporting

confidence: 89%

Effects of Norethandrolone on the Transport and Peripheral Metabolism of Thyroxine in Patients Lacking Thyroxine-Binding Globulin

Braverman¹,

AvRuskin²,

Cullen³

et al. 1971

J. Clin. Invest.

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“…FT4, determined in all three families, proved to be normal or slightly reduced, as also reported by others (1,2,3,8,10) in persons with TBG deficiency.…”

Section: Discussionsupporting

confidence: 88%

Familial Thyroxine‐binding Globulin Deficiency

Strunge

1974

Journal of Internal Medicine

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Three Danish pedigrees have been studied with a view to reduced thyroxine-binding globulin (TBG). The study confirmed that this defect is transmitted by Xchromosome-linked dominant inheritance, there being no man-to-man transmission, but also that it may occur in two types: deficient TBG and low, non-zero TBG. Definite changes of TBG and thyroid function tests were found in the hemizygous men, whereas the heterozygous women showed a marked variation in the range between the values for hemizygous men and normal persons. Determination of total thyroxine appears to afford more guidance than the protein-bound iodine suggested by others. Two of four women on oral contraception exhibited such deviating TBG values that they are assumed to be TBG heterozygous. In all persons free thyroxine proved normal or slightly reduced but all the persons tested were euthyroid. However, the propositus of one family had previously been treated for Graves' disease.

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“…We have previously analyzed published data on 24 families from which it was concluded that although only in one-third of the families was X-chromosome-linked transmission suggested by the authors, the remaining kindreds showed no evidence of incompatibility with such mode of inheritance (3). With a single exception (12), a similar conclusion can be drawn from the analyses of 10 pedigrees with TBG abnormalities published since our previous review (7,8,12,(28)(29)(30)(31)(32)(33) and from the two new families presented. The family in question included an XX female, brother, and son with undetectable serum TBG, reduced TBG in a daughter, and normal TBG in the parents (12).…”

Section: Clinical Materialssupporting

confidence: 67%

“…The observed changes in T4 kinetics seem to be related to changes in the fractional turnover rate and/or the extrathyroidal T4 pool associated with the increased or decreased total T4-binding capacity of TBG in serum (5). Though some reports have indicated that the free T4 concentration may be altered in the serum of subj ects with changes in the T4 capacity of TBG (6)(7)(8), the bulk of evidence and the hormone kinetic studies suggest that the free T4 level in serum remains within the normal range and that it determines the thyroid hormone-dependent metabolic status of the subjects.…”

Section: Introductionmentioning

confidence: 99%

Metabolism of thyroxine-binding globulin in man. Abnormal rate of synthesis in inherited thyroxine-binding globulin deficiency and excess.

Refetoff¹,

Fang²,

Marshall³

et al. 1976

J. Clin. Invest.

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A B S T R A C T It has been previously suggested that inherited thyroxine-binding globulin (TBG) abnormalities in man may be due to mutations at a single X-chromosome-linked locus controlling TBG synthesis. However, abnormalities in TBG degradation have not been excluded. The availability of purified human TBG and its successful labeling with radioiodide allowed us to examine such possibility.Human TBG was purified by affinity chromatography, labeled under sterile conditions with 'I or 'I, and mixed with ['I]thyroxine (T4) or ['I] T4, respectively, before their intravenous injection. Blood and urine samples were collected over a 10-day period, and the turnover parameters were calculated. In eight normal volunteers mean values +SD for TBG and T4 respectively, were as follows: Half time (ti) 5.3±0.4 and 7.0±0.6 days; distribution space (DS) 7.2± 1.0 and 10.8± 1.2 liters; and total daily degradation (D) 0.211±0.053 and 0.088±0.011 /smol/day. In all subjects, ti of TBG was shorter than that of T4; and the DS was smaller. 2.4 mol of TBG was degraded for each mole of T4. In five of six subjects from four families, comprising hemizygous and heterozygous carriers of TBG absence, decrease, and excess, the ti and DS for TBG were within the normal range. The D of TBG was proportional to the serum concentration of the protein. Changes in the T4 kinetics in these patients were compatible with euthyroidism and with the known alterations in the extrathyroidal T4 pool This work was published in part in abstract form (1973. Clin. Res. 21: 201) and was presented in part at the 49th Annual Meeting of the American Thyroid Association, Seattle, Wash., 12-15 September 1973. Received for publication 27 January 1975 and in revised form 18 October 1975. associated with the changes in serum TBG concentration. A striking decrease in the ti of TBG was found only in a patient with acquired diminution in TBG concentration and in patients with thyrotoxicosis or other conditions apparently unrelated to thyroid dysfunction.TBG ti was 2.5 days in a patient with multiple myeloma and 3.6 days in two patients with thyrotoxicosis. Decreased TBG ti was also observed in three of six patients with nonthyroidal pathology and was associated with an increase in TBG D disproportionate to their level of serum TBG.These studies indicate that changes in TBG concentration in patients with X-chromosome-linked TBG abnormalities are due to alterations in its rate of synthesis. In other conditions, abnormalities of TBG degradation and/or rate of synthesis may be found.

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Relationship Between Total Thyroxine and Absolute Free Thyroxine and the Influence of Absolute Free Thyroxine on Thyroxine Disposal in Humans¹

Cited by 25 publications

References 15 publications

Effects of Norethandrolone on the Transport and Peripheral Metabolism of Thyroxine in Patients Lacking Thyroxine-Binding Globulin

Effects of Norethandrolone on the Transport and Peripheral Metabolism of Thyroxine in Patients Lacking Thyroxine-Binding Globulin

Familial Thyroxine‐binding Globulin Deficiency

Metabolism of thyroxine-binding globulin in man. Abnormal rate of synthesis in inherited thyroxine-binding globulin deficiency and excess.

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Relationship Between Total Thyroxine and Absolute Free Thyroxine and the Influence of Absolute Free Thyroxine on Thyroxine Disposal in Humans1

Cited by 25 publications

References 15 publications

Effects of Norethandrolone on the Transport and Peripheral Metabolism of Thyroxine in Patients Lacking Thyroxine-Binding Globulin

Effects of Norethandrolone on the Transport and Peripheral Metabolism of Thyroxine in Patients Lacking Thyroxine-Binding Globulin

Familial Thyroxine‐binding Globulin Deficiency

Metabolism of thyroxine-binding globulin in man. Abnormal rate of synthesis in inherited thyroxine-binding globulin deficiency and excess.

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Relationship Between Total Thyroxine and Absolute Free Thyroxine and the Influence of Absolute Free Thyroxine on Thyroxine Disposal in Humans¹