Effect of Sodium Ethylmercurithiosalicylate (Thimerosal) on Serum Binding of Thyroid Hormones

1973 ◽  
Vol 51 (2) ◽  
pp. 156-159 ◽  
Author(s):  
Diego Bellabarba ◽  
Raymonde Tremblay
Keyword(s):  
Thyroid Hormones ◽  
Binding Proteins ◽  
Serum Proteins ◽  
Free Fraction ◽  
Inhibitory Effect ◽  
Free T4 ◽  
Thyroxine Binding Globulin ◽  
Free T3 ◽  
Serum Binding Protein ◽  
Barbital Buffer

Sodium ethylmercurithiosalicylate (Thimerosal, Merthiolate) has been found to interfere with the binding of thyroid hormones to serum proteins. Dialysis studies showed that this compound, added to serum in concentrations varying from 90 to 360 mg/100 ml, caused an increase of the dialyzable or free fraction of thyroxine (T4) and triiodothyronine (T3). The increase was higher for the free T4 (3.8- to 18-fold) than for the free T3 fraction (2.3- to 5-fold). Electrophoretic studies on the distribution of tracer amounts of labeled T4 among the serum binding proteins revealed that the inhibitory effect of sodium ethylmercurithiosalicylate was exerted mainly on thyroxine binding globulin (TBG). In presence of this compound (180 mg/100 ml of serum) the percentage of tracer T4 bound to TBG was reduced from 53% to 9%. These findings were also confirmed by examining the binding of tracer amounts of labeled T4 and T3 in a serum diluted in barbital buffer, which inhibits the hormonal binding to thyroxine binding prealbumin and albumin. In presence of sodium ethylmercurithiosalicylate a significant displacement of both T4 and T3 from the serum binding protein (TBG) was observed.

The Transport of Thyroid Hormones

1983 ◽  
Vol 65 (4) ◽  
pp. 337-342 ◽  
Author(s):  
R. Hoffenberg ◽  
D. B. Ramsden
Keyword(s):  
Thyroid Hormones ◽  
Binding Proteins ◽  
Serum Proteins ◽  
High Capacity ◽  
Free Fraction ◽  
Total Serum ◽  
Free T4 ◽  
Specific Serum ◽  
Target Organs ◽  
Serum T4

1. Hormones have to be transported from their sites of synthesis to their target organs. For lipophilic hormones, such as steroids and thyroid hormones, transport is accomplished by binding to specific serum proteins, in the case of thyroxine (T4) and tri-iodothyronine (T3) to thyroxine-binding globulin (TBG) and prealbumin (PA). Normally about 70% of circulating T4 and 75–80% of T3 is bound to TBG, about 20% of T4 and 10% of T3 to PA and 10–15% of each to albumin, which has a low affinity but high capacity for both hormones [1, 2]. Apart from facilitating transport, binding to serum protein prevents excessive loss of hormone into the urine by glomerular filtration or flooding into cells, and may provide a readily available reservoir in times of need. The union between binding proteins and their ligands is reversible, so that a small proportion of hormone is non-protein-bound or ‘free’, in equilibrium with that which is protein-bound. For T4 this free fraction is normally 0.02-0.04% of the total serum T4 concentration, for T3 about 0.3% [3, 4]. 2. The major binding proteins of T4 and T3 will briefly be described and the nature of free T4 and T3 considered.

scholarly journals Quantifying Spurious Free T4 Results Attributable to Thyroxine-Binding Proteins in Serum Dialysates and Ultrafiltrates

2007 ◽  
Vol 53 (5) ◽  
pp. 985-988 ◽  
Author(s):  
Kristofer S Fritz ◽  
R Bruce Wilcox ◽  
Jerald C Nelson
Keyword(s):  
Serum Protein ◽  
Total Protein ◽  
Binding Proteins ◽  
Serum Proteins ◽  
Equilibrium Dialysis ◽  
Free T4 ◽  
Serum Total Protein ◽  
Semipermeable Membranes ◽  
Serum Free ◽  
Thyroxine Binding Globulin

Abstract Background: Direct equilibrium dialysis and direct ultrafiltration free thyroxine (T4) assays rely on semipermeable membranes to exclude T4-binding serum proteins from dialysates and ultrafiltrates. The presence of these proteins in dialysates or ultrafiltrates will yield spuriously high free T4 values when free T4 is quantified by RIA. Methods: We used a nonanalog free T4 RIA that detects and quantifies dialyzable and ultrafilterable serum free T4 to detect T4-binding serum proteins. Two equilibrium dialysis devices and 3 ultrafiltration devices were used to illustrate this application. Displacements of [125I]T4 from anti-T4 by various concentrations of T4-depleted thyroxine-binding globulin, albumin, and serum total protein were compared to displacements by various concentrations of free T4. Results: Both dialysis devices excluded detectable T4-binding serum proteins from dialysates. Two of 3 ultrafiltration devices excluded detectable T4-binding serum proteins from ultrafiltrates. One did not, and its ultrafiltrate yielded spurious free T4 values that correlated directly with serum protein concentrations. Conclusion: The presence or absence of T4-binding proteins in dialysates and ultrafiltrates and the spurious free T4 values that these proteins cause can be documented using a nonanalog free T4 RIA.

Free triiodothyronine and free thyroxin in sera of pregnant women and subjects with congenitally increased or decreased thyroxin-binding globulin.

1983 ◽  
Vol 29 (8) ◽  
pp. 1527-1530 ◽  
Author(s):  
J A Franklyn ◽  
M C Sheppard ◽  
D B Ramsden ◽  
R Hoffenberg
Keyword(s):  
Pregnant Women ◽  
Binding Proteins ◽  
Free Triiodothyronine ◽  
Free T4 ◽  
Free T3 ◽  
Low Concentrations ◽  
Euthyroid Status ◽  
In Pregnancy

Abstract Concentrations of free thyroxin (T4) and free triiodothyronine (T3) were measured in sera from pregnant women, in subjects with congenitally increased or decreased thyroxin-binding globulin (TBG), and in euthyroid controls. Measured free hormone concentrations were compared with calculated values for free hormone derived from concentrations of total T4, total T3, and binding proteins. Measured and calculated concentrations of free T4 and free T3 were below normal in the pregnant subjects but were normal in subjects with congenital increases of TBG. The low concentrations of free hormone in pregnancy are at variance with the euthyroid status of these subjects. Measured free T4 was normal, but concentrations of free T3 were less in the euthyroid congenitally low-TBG group.

scholarly journals Cold Exposure Distinctively Modulates Parathyroid and Thyroid Hormones in Cold-Acclimatized and Non-Acclimatized Humans

Endocrinology ◽  
2020 ◽  
Vol 161 (7) ◽  
Author(s):  
Zuzana Kovaničová ◽  
Tímea Kurdiová ◽  
Miroslav Baláž ◽  
Patrik Štefanička ◽  
Lukáš Varga ◽  
...  
Keyword(s):  
Thyroid Hormones ◽  
Cold Exposure ◽  
Neck Surgery ◽  
Whole Body ◽  
Free T4 ◽  
Free T3 ◽  
Brown Adipose ◽  
Induced Changes ◽  
Ice Water

Abstract Cold-induced activation of thermogenesis modulates energy metabolism, but the role of humoral mediators is not completely understood. We aimed to investigate the role of parathyroid and thyroid hormones in acute and adaptive response to cold in humans. Examinations were performed before/after 15 minutes of ice-water swimming (n = 15) or 120 to 150 minutes of cold-induced nonshivering thermogenesis (NST) applied to cold-acclimatized (n = 6) or non-acclimatized (n = 11) individuals. Deep-neck brown adipose tissue (BAT) was collected from non-acclimatized patients undergoing elective neck surgery (n = 36). Seasonal variations in metabolic/hormonal parameters of ice-water swimmers were evaluated. We found that in ice-water swimmers, PTH and TSH increased and free T3, T4 decreased after a 15-minute winter swim, whereas NST-inducing cold exposure failed to regulate PTH and free T4 and lowered TSH and free T3. Ice-water swimming-induced increase in PTH correlated negatively with systemic calcium and positively with phosphorus. In non-acclimatized men, NST-inducing cold decreased PTH and TSH. Positive correlation between systemic levels of PTH and whole-body metabolic preference for lipids as well as BAT volume was found across the 2 populations. Moreover, NST-cooling protocol-induced changes in metabolic preference for lipids correlated positively with changes in PTH. Finally, variability in circulating PTH correlated positively with UCP1/UCP1, PPARGC1A, and DIO2 in BAT from neck surgery patients. Our data suggest that regulation of PTH and thyroid hormones during cold exposure in humans varies by cold acclimatization level and/or cold stimulus intensity. Possible role of PTH in NST is indicated by its positive relationships with whole-body metabolic preference for lipids, BAT volume, and UCP1 content.

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

2007 ◽  
Vol 53 (5) ◽  
pp. 911-915 ◽  
Author(s):  
Kristofer S Fritz ◽  
R Bruce Wilcox ◽  
Jerald C Nelson
Keyword(s):  
Serum Protein ◽  
Binding Proteins ◽  
Serum Proteins ◽  
Equilibrium Dialysis ◽  
Free Thyroxine ◽  
Free T4 ◽  
Serum T4 ◽  
Presence And Absence

Abstract Background: Direct free thyroxine (T4) measurements have been linked to both T4-binding serum protein concentrations and protein-bound T4 concentrations. Whether this is evidence of a relationship to total T4 concentrations has not been reported. Methods: We compared an analog-based direct free T4 immunoassay and a total T4 immunoassay. Each assay was applied to the fractions of serum T4 obtained by ultrafiltration and equilibrium dialysis. Both were applied to serum-based solutions in which free T4, T4-binding proteins, protein-bound T4, and total T4 were systematically varied, held constant, or excluded. Results: Neither the free T4 assay nor the total T4 assay detected dialyzable or ultrafilterable serum T4. Both assays detected and reported the T4 retained with serum proteins. Both free and total T4 results were related to the same total T4 concentrations in the presence and absence of T4-binding proteins. Both results were similarly related to total T4 concentrations when free T4 was held constant while total T4 was varied. Both were similarly related to a total T4 concentration that was held constant while free T4 progressively replaced protein-bound T4. These free T4 results, like total T4 results, were unresponsive to a 500-fold variation in dialyzable T4 concentrations. Conclusion: New experiments extend the characterization of a longstanding and incompletely characterized analog-based free T4 immunoassay. These free T4 measurements relate to total T4 concentrations in the same way that total T4 measurements do.

Radioimmunoassay for Serum Triiodothyronine: Evaluation of Simple Techniques to Control Interference from Binding Proteins

1974 ◽  
Vol 20 (9) ◽  
pp. 1150-1154 ◽  
Author(s):  
Victor S Fang ◽  
Samuel Refetoff
Keyword(s):  
Binding Sites ◽  
Binding Proteins ◽  
Serum Proteins ◽  
Cross Reactivity ◽  
Heat Inactivation ◽  
Nonspecific Binding ◽  
High Concentration ◽  
Assay Sensitivity ◽  
Thyroxine Binding Globulin ◽  
Fixed Concentration

Abstract Simple techniques for controlling interference from binding proteins in serum, such as thyroxine-binding globulin, in radioimmunoassay for triiodothyronine (T3) have been evaluated for their efficacy, and their effect on assay sensitivity and on recovery of added T3. Ethanol precipitation of serum proteins decreased the assay sensitivity, nonspecific binding was increased, and recoveries of added T3 were inconsistent. Heat-inactivation of thyroxine-binding globulin or use of 8-anilino-1naphthalene sulfonic acid (ANS) to displace T3 from thyroxine-binding globulin produced comparable recovery rates. The heat-inactivation method slightly decreased the sensitivity of the assay and prolonged the procedure, whereas use of ANS is simple, and the assay sensitivity is maintained. When sera contain a high concentration of thyroxine-binding globulin, a fixed concentration of ANS (175 µg/100 µl of serum) might be too low to displace T3 from all its binding sites, but a concentration of ANS greater than 200 µg/100 µl of serum interferes with T3 quantitation by competitively binding to the antibodies. The cross-reactivity of thyroxine to T3-antibodies varies with the antiserum. Thyroxine-binding globulin appears to be the only protein in serum that competes with the antibody for T3 binding.

A Reassessment of 8-Anilino-1-Naphthalene Sulphonic Acid as a Thyroxine Binding Inhibitor in the Radioimmunoassay of Thyroxine

1977 ◽  
Vol 14 (1-6) ◽  
pp. 330-334 ◽  
Author(s):  
S. E. Evans ◽  
W. A. Burr ◽  
T. C. Hogan
Keyword(s):  
Polyethylene Glycol ◽  
Binding Proteins ◽  
Serum Proteins ◽  
Sulphonic Acid ◽  
Thyroxine Binding Globulin ◽  
Double Antibody ◽  
Resin Separation

The effectiveness of 8-anilino-1-naphthalene sulphonic acid (ANS) in the radioimmunoassay (RIA) of thyroxine (T4) as an inhibitor of the binding of T4 to serum T4-binding proteins is assessed. The optimum ANS concentration is dependent upon the antiserum and the method used for separating free and bound T4. If T4 binding to serum proteins is not completely inhibited, resin separation methods may yield low values, while polyethylene glycol and double-antibody methods may produce high values for T4 concentration. Even with optimum ANS concentration gross errors in measurement of T4 may occur in patients with high thyroxine-binding globulin (TBG) concentrations.

scholarly journals Adherence to a Mediterranean Diet and Thyroid Function in Obesity: A Cross-Sectional Apulian Survey

Nutrients ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 3173
Author(s):  
Roberta Zupo ◽  
Fabio Castellana ◽  
Francesco Panza ◽  
Luisa Lampignano ◽  
Isanna Murro ◽  
...  
Keyword(s):  
Thyroid Hormones ◽  
Mediterranean Diet ◽  
Thyroid Function ◽  
Serum Levels ◽  
Overweight And Obesity ◽  
Free T4 ◽  
Cross Sectional ◽  
Free T3 ◽  
Obese Subjects ◽  
The Relationship

Much research suggests that Mediterranean eating habits and lifestyle contribute to counteract the risk of chronic diseases while promoting longevity, but little information is available on the effects of the Mediterranean diet (Med-Diet) on thyroid function, particularly among overweight/obese subjects. Nevertheless, consistent data reported a slight increase in serum levels of the thyroid-stimulating hormone (TSH) and a higher rate of conversion of thyroxine (T4) to triiodothyronine (T3) in obesity. This cross-sectional study was aimed at investigating the relationship between adherence to the Med-Diet and circulating thyroid hormones in a cohort of overweight/obese subjects from Apulia (Southern Italy). Methods: We studied 324 consecutive outpatient subjects (228 women and 96 men, age range 14–72 years) taking no drug therapy and showing normal levels of thyroid hormones, but complicated by overweight and obesity (body mass index (BMI) ≥ 25 Kg/m2). The PREDIMED (PREvención con DIeta MEDiterránea) questionnaire was cross-sectionally administered to assess the adherence to the Med-Diet, and hormonal, metabolic, and routine laboratory parameters were collected. Results: Higher adherence to Med-Diet was found to be inversely related to free T3 (p < 0.01) and T4 (p < 0.01) serum levels. Considering each item in the PREDIMED questionnaire, people consuming at least four spoonfuls of extra-virgin olive oil (EVOO) per day, as well as those consuming at least two servings of vegetables per day, had lower free T3 levels (p 0.033 and p 0.021, respectively). Furthermore, consuming at least four spoonfuls of EVOO per day was found to be associated to lower free T4 serum concentrations (p 0.011). Multinomial logistic regression models, performed on tertiles of thyroid hormones to further investigate the relationship with Med-Diet, corroborated the significance only for free T4. Conclusion: Increased adherence to the Med-Diet was independently associated to a slightly reduced thyroid function, but still within the reference range for free T3 and T4 serum levels. This first finding in this field opens up a research line on any underlying biological interplay.

Decreased free fraction of thyroid hormones after prolonged Antarctic residence

1990 ◽  
Vol 69 (4) ◽  
pp. 1467-1472 ◽  
Author(s):  
H. L. Reed ◽  
D. Brice ◽  
K. M. Shakir ◽  
K. D. Burman ◽  
M. M. D'Alesandro ◽  
...  
Keyword(s):  
Thyroid Hormones ◽  
Free Fraction ◽  
Cardiovascular Responses ◽  
Free T4 ◽  
Before And After ◽  
Total Triiodothyronine ◽  
Serum T3 ◽  
Total Thyroxine ◽  
Normal Men ◽  
First Time

We investigated the effects of Antarctic residence (AR) on serum thyroid hormone and cardiovascular responses to a 60-min standard cold air (0 degree C) test (SCAT). Serum total thyroxine (TT4) and serum total triiodothyronine (TT3), free T4 (FT4) and T3 (FT3), thyrotropin (TSH), and percent free fraction of T4 (%FT4) and T3 (%FT3) were measured in normal men (n = 15) before and after each of three SCATs. The SCAT was first carried out in California and then repeated after 24 and 44 wk AR. Mean arterial pressure (MAP) and sublingual oral temperature (Tor) were measured before and during each SCAT. The SCAT did not alter thyroid hormones before or after AR. The %FT4 decreased from 0.0334 +/- 0.0017 to 0.0295 +/- 0.0007% (P less than 0.002) with 44 wk AR but without a significant change in TT4 or FT4 for the same period. The %FT3 also decreased from 0.2812 +/- 0.0128 to 0.2458 +/- 0.0067% (P less than 0.005) after 44 wk AR. FT3 decreased (P less than 0.003) but TT3 and TSH were unchanged with 44 wk AR. The decrease in %FT4 and %FT3 may be theoretically accounted for by a 10% increase in either the capacity or the affinity of the serum binding proteins. The SCAT in California increased MAP and did not change Tor. After 44 wk AR, the SCAT no longer increased MAP but did lower Tor. The shift in the Tor and MAP response to the SCAT is consistent with the associated occurrence of cold adaptation during AR. We describe for the first time a decrease in the free fraction of both serum T3 and T4 present with extended polar residence and independent of a SCAT, further characterizing the recently reported “polar T3 syndrome.”

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