Thyroxine Transport Proteins of Plasma. Molecular Properties and Biosynthesis

Robbins, Jacob; Cheng, Sheue-yann; Gershengorn, Marvin C.; Glinoer, Daniel; Cahnmann, H. J.; Edelnoch, Harold

doi:10.1016/b978-0-12-571134-0.50017-x

Cited by 82 publications

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“…The best characterized effect of estrogens is a dose-dependent increase of serum thyroxine-binding globulin (TBG), due to both a decrease in the clearance of heavily sialyated TBG secreted by the liver (24) and an increase in its biosynthesis (25). Recent data indicate that women with primary hypothyroidism need a higher T 4 dose when under estrogen treatment (26).…”

Section: Discussionmentioning

confidence: 99%

Clinical and hormonal characteristics of central hypothyroidism at diagnosis and during follow-up in adult patients

et al. 2004

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Objective: We studied the clinical and hormonal profiles of patients with central hypothyroidism (CH), the adequacy of levothyroxine (L-T4) treatment and the influence of other pituitary hormone replacement therapies. Methods: We reviewed medical records of 108 adult patients with child-onset (CO; n ¼ 26) or adultonset (AO; n ¼ 82) CH. Results: At diagnosis, the most frequently reported symptoms were fatigue and headaches in AO patients, and growth retardation in CO patients. Serum TSH was normal in a majority of CH patients, low in 8% and elevated in 8%. Serum free thyroxine (fT 4 ) was usually reduced, but remained within the low normal range in 28% of the study population (mostly CO patients). Similarly, serum total T 4 (tT 4 ), total triiodothyronine (tT 3 ) and free T 3 (fT 3 ) were found to be within the normal range in significant subsets of patients. Interestingly, the clinical and biochemical characteristics of CH patients with normal f/t T 4 levels were not different from those of the patients with low fT 4 values. The thyroid hormonal profile was not influenced by gender, etiology or by the number of hormone deficiencies. At last evaluation, the mean dose of L-T 4 was 1.6^0.5 mg/kg/day and was negatively correlated to current age (P , 0.001) but positively correlated to the number of hormone deficiencies (P , 0.05). Treatment suppressed TSH in 75% of the patients, induced normal fT 4 in 94%, but normal fT 3 in only 49% of them. Male GH-treated patients and estrogen-treated females needed a higher L-T 4 dose compared with non-treated patients. Conclusions: fT 4 is clearly the best indicator of CH, but remains in the low normal range in a significant subset of patients, especially in those with CO disease. Adequacy of therapy is mostly reflected by the combination of upper normal fT 4 and low normal fT 3 levels. Pituitary hormone replacement therapy may require an adjustment of T 4 treatment, as female patients under estrogen treatment and male patients under GH treatment will need a higher T 4 dose in order to remain in the euthyroid range.European Journal of Endocrinology 150 1-8

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Section: Discussionmentioning

confidence: 99%

Clinical and hormonal characteristics of central hypothyroidism at diagnosis and during follow-up in adult patients

et al. 2004

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“…Protein-bound and total T 4 concentrations vary (correlate) directly with free T 4 concentrations when serum T 4 -binding proteins are constant. When free T 4 is constant, protein-bound T 4 and total T 4 concentrations vary directly with concentrations of T 4 -binding proteins.…”

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confidence: 99%

“…When free T 4 is constant, protein-bound T 4 and total T 4 concentrations vary directly with concentrations of T 4 -binding proteins. There are reports of direct analog-based free T 4 results that vary directly with serum concentrations of T 4 -binding protein (7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18) or vary as total T 4 concentrations vary (while free T 4 is held constant) (19,20 ). These relationships imply that these analog-based direct free T 4 assays detect total T 4 concentrations.…”

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confidence: 99%

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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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“…The respective affinities of the three binding proteins for TH are not significantly modified. Hence, the proportion of T4 carried by TBG reaches 75% during gestation [14].…”

Section: Thyroid Hormones Transport Proteinsmentioning

confidence: 98%