Negative bias from analog methods used in the analysis of free thyroxine in rat serum containing perfluorooctanesulfonate (PFOS)

Shu Ching Chang, Julie R. Thibodeaux, Mary L. Eastvold, David J. Ehresman, James A. Bjork, John W. Froehlich, Christopher S. Lau, Ravinder Jit Singh, Kendall B. Wallace, John L. Butenhoff

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

Decreases in serum total thyroxine (TT4) and free thyroxine (FT4) without a compensatory rise in thyroid stimulating hormone (thyrotropin or TSH) or histological changes of the thyroid have been observed in studies with perfluorooctanesulfonate (PFOS) treatments in rats. Prior observations do not fit the clinical profile of a hypothyroid state. PFOS is known to compete with fatty acids for albumin binding, and serum free fatty acids (FFA) are known to interfere with FT4 measurement using analog methods due to competition for protein binding. Therefore, we hypothesized that measured decreases in serum FT4 by analog methods in the presence of PFOS were due to carrier protein binding interference. We compared FT4 analog assay methods with a reference method using equilibrium dialysis (ED-RIA) for FT4 measurement in rat sera in vitro and in vivo. We also measured hepatic malic enzyme mRNA transcripts and activity as a marker for hepatic thyroid hormone response. PFOS did not reduce serum TT4 and FT4 in vitro at concentrations up to 200 μM. After three daily 5 mg/kg oral doses of potassium PFOS to female rats, serum TSH and FT4 by ED-RIA were unchanged (although FT4 determined by two common analog methods was decreased), and malic enzyme was not suppressed. These data suggest that prior reports of reduced free thyroid hormone in the presence of PFOS were due to negative bias in analog methods and that short-term PFOS treatment does not suppress the physiological thyroid status in rats. A reference method such as ED-RIA should be used for determination of serum FT4 in the presence of PFOS.

Original languageEnglish (US)
Pages (from-to)21-33
Number of pages13
JournalToxicology
Volume234
Issue number1-2
DOIs
StatePublished - May 5 2007

Fingerprint

Thyroxine
Rats
Serum
Thyrotropin
Thyroid Hormones
Protein Binding
Thyroid Gland
Dialysis
perfluorooctane sulfonic acid
Liver
Enzymes
Nonesterified Fatty Acids
Serum Albumin
Albumins
Assays
Potassium
Carrier Proteins
Fatty Acids
Messenger RNA

Keywords

  • Analog method
  • Equilibrium dialysis
  • Negative bias
  • Perfluorooctanesulfonate (PFOS)
  • Rats
  • Thyroid hormones

ASJC Scopus subject areas

  • Toxicology

Cite this

Chang, S. C., Thibodeaux, J. R., Eastvold, M. L., Ehresman, D. J., Bjork, J. A., Froehlich, J. W., ... Butenhoff, J. L. (2007). Negative bias from analog methods used in the analysis of free thyroxine in rat serum containing perfluorooctanesulfonate (PFOS). Toxicology, 234(1-2), 21-33. https://doi.org/10.1016/j.tox.2007.01.020

Negative bias from analog methods used in the analysis of free thyroxine in rat serum containing perfluorooctanesulfonate (PFOS). / Chang, Shu Ching; Thibodeaux, Julie R.; Eastvold, Mary L.; Ehresman, David J.; Bjork, James A.; Froehlich, John W.; Lau, Christopher S.; Singh, Ravinder Jit; Wallace, Kendall B.; Butenhoff, John L.

In: Toxicology, Vol. 234, No. 1-2, 05.05.2007, p. 21-33.

Research output: Contribution to journalArticle

Chang, SC, Thibodeaux, JR, Eastvold, ML, Ehresman, DJ, Bjork, JA, Froehlich, JW, Lau, CS, Singh, RJ, Wallace, KB & Butenhoff, JL 2007, 'Negative bias from analog methods used in the analysis of free thyroxine in rat serum containing perfluorooctanesulfonate (PFOS)', Toxicology, vol. 234, no. 1-2, pp. 21-33. https://doi.org/10.1016/j.tox.2007.01.020
Chang, Shu Ching ; Thibodeaux, Julie R. ; Eastvold, Mary L. ; Ehresman, David J. ; Bjork, James A. ; Froehlich, John W. ; Lau, Christopher S. ; Singh, Ravinder Jit ; Wallace, Kendall B. ; Butenhoff, John L. / Negative bias from analog methods used in the analysis of free thyroxine in rat serum containing perfluorooctanesulfonate (PFOS). In: Toxicology. 2007 ; Vol. 234, No. 1-2. pp. 21-33.
@article{dccaeff969cc44b4818b0f8aa86a92cf,
title = "Negative bias from analog methods used in the analysis of free thyroxine in rat serum containing perfluorooctanesulfonate (PFOS)",
abstract = "Decreases in serum total thyroxine (TT4) and free thyroxine (FT4) without a compensatory rise in thyroid stimulating hormone (thyrotropin or TSH) or histological changes of the thyroid have been observed in studies with perfluorooctanesulfonate (PFOS) treatments in rats. Prior observations do not fit the clinical profile of a hypothyroid state. PFOS is known to compete with fatty acids for albumin binding, and serum free fatty acids (FFA) are known to interfere with FT4 measurement using analog methods due to competition for protein binding. Therefore, we hypothesized that measured decreases in serum FT4 by analog methods in the presence of PFOS were due to carrier protein binding interference. We compared FT4 analog assay methods with a reference method using equilibrium dialysis (ED-RIA) for FT4 measurement in rat sera in vitro and in vivo. We also measured hepatic malic enzyme mRNA transcripts and activity as a marker for hepatic thyroid hormone response. PFOS did not reduce serum TT4 and FT4 in vitro at concentrations up to 200 μM. After three daily 5 mg/kg oral doses of potassium PFOS to female rats, serum TSH and FT4 by ED-RIA were unchanged (although FT4 determined by two common analog methods was decreased), and malic enzyme was not suppressed. These data suggest that prior reports of reduced free thyroid hormone in the presence of PFOS were due to negative bias in analog methods and that short-term PFOS treatment does not suppress the physiological thyroid status in rats. A reference method such as ED-RIA should be used for determination of serum FT4 in the presence of PFOS.",
keywords = "Analog method, Equilibrium dialysis, Negative bias, Perfluorooctanesulfonate (PFOS), Rats, Thyroid hormones",
author = "Chang, {Shu Ching} and Thibodeaux, {Julie R.} and Eastvold, {Mary L.} and Ehresman, {David J.} and Bjork, {James A.} and Froehlich, {John W.} and Lau, {Christopher S.} and Singh, {Ravinder Jit} and Wallace, {Kendall B.} and Butenhoff, {John L.}",
year = "2007",
month = "5",
day = "5",
doi = "10.1016/j.tox.2007.01.020",
language = "English (US)",
volume = "234",
pages = "21--33",
journal = "Toxicology",
issn = "0300-483X",
publisher = "Elsevier Ireland Ltd",
number = "1-2",

}

TY - JOUR

T1 - Negative bias from analog methods used in the analysis of free thyroxine in rat serum containing perfluorooctanesulfonate (PFOS)

AU - Chang, Shu Ching

AU - Thibodeaux, Julie R.

AU - Eastvold, Mary L.

AU - Ehresman, David J.

AU - Bjork, James A.

AU - Froehlich, John W.

AU - Lau, Christopher S.

AU - Singh, Ravinder Jit

AU - Wallace, Kendall B.

AU - Butenhoff, John L.

PY - 2007/5/5

Y1 - 2007/5/5

N2 - Decreases in serum total thyroxine (TT4) and free thyroxine (FT4) without a compensatory rise in thyroid stimulating hormone (thyrotropin or TSH) or histological changes of the thyroid have been observed in studies with perfluorooctanesulfonate (PFOS) treatments in rats. Prior observations do not fit the clinical profile of a hypothyroid state. PFOS is known to compete with fatty acids for albumin binding, and serum free fatty acids (FFA) are known to interfere with FT4 measurement using analog methods due to competition for protein binding. Therefore, we hypothesized that measured decreases in serum FT4 by analog methods in the presence of PFOS were due to carrier protein binding interference. We compared FT4 analog assay methods with a reference method using equilibrium dialysis (ED-RIA) for FT4 measurement in rat sera in vitro and in vivo. We also measured hepatic malic enzyme mRNA transcripts and activity as a marker for hepatic thyroid hormone response. PFOS did not reduce serum TT4 and FT4 in vitro at concentrations up to 200 μM. After three daily 5 mg/kg oral doses of potassium PFOS to female rats, serum TSH and FT4 by ED-RIA were unchanged (although FT4 determined by two common analog methods was decreased), and malic enzyme was not suppressed. These data suggest that prior reports of reduced free thyroid hormone in the presence of PFOS were due to negative bias in analog methods and that short-term PFOS treatment does not suppress the physiological thyroid status in rats. A reference method such as ED-RIA should be used for determination of serum FT4 in the presence of PFOS.

AB - Decreases in serum total thyroxine (TT4) and free thyroxine (FT4) without a compensatory rise in thyroid stimulating hormone (thyrotropin or TSH) or histological changes of the thyroid have been observed in studies with perfluorooctanesulfonate (PFOS) treatments in rats. Prior observations do not fit the clinical profile of a hypothyroid state. PFOS is known to compete with fatty acids for albumin binding, and serum free fatty acids (FFA) are known to interfere with FT4 measurement using analog methods due to competition for protein binding. Therefore, we hypothesized that measured decreases in serum FT4 by analog methods in the presence of PFOS were due to carrier protein binding interference. We compared FT4 analog assay methods with a reference method using equilibrium dialysis (ED-RIA) for FT4 measurement in rat sera in vitro and in vivo. We also measured hepatic malic enzyme mRNA transcripts and activity as a marker for hepatic thyroid hormone response. PFOS did not reduce serum TT4 and FT4 in vitro at concentrations up to 200 μM. After three daily 5 mg/kg oral doses of potassium PFOS to female rats, serum TSH and FT4 by ED-RIA were unchanged (although FT4 determined by two common analog methods was decreased), and malic enzyme was not suppressed. These data suggest that prior reports of reduced free thyroid hormone in the presence of PFOS were due to negative bias in analog methods and that short-term PFOS treatment does not suppress the physiological thyroid status in rats. A reference method such as ED-RIA should be used for determination of serum FT4 in the presence of PFOS.

KW - Analog method

KW - Equilibrium dialysis

KW - Negative bias

KW - Perfluorooctanesulfonate (PFOS)

KW - Rats

KW - Thyroid hormones

UR - http://www.scopus.com/inward/record.url?scp=34047167383&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34047167383&partnerID=8YFLogxK

U2 - 10.1016/j.tox.2007.01.020

DO - 10.1016/j.tox.2007.01.020

M3 - Article

C2 - 17368689

AN - SCOPUS:34047167383

VL - 234

SP - 21

EP - 33

JO - Toxicology

JF - Toxicology

SN - 0300-483X

IS - 1-2

ER -