Journal of Endocrinological Investigation

, Volume 38, Issue 8, pp 885–890 | Cite as

Ischemia-modified albumin levels in overt and subclinical hypothyroidism

  • S. V. Reddy
  • M. M. Suchitra
  • V. Pradeep
  • S. Alok
  • V. Suresh
  • A. R. Bitla
  • P. V. L. N. Srinivasa Rao
Original Article

Abstract

Background

Free radical-mediated oxidative stress (OS) has been implicated in the pathogenesis of thyroid disorders. The ischemia-modified albumin (IMA) has been proposed as a marker of protein oxidative damage, which has been found to reflect hypoxic stress.

Aim

Our aim was to evaluate IMA, malondialdehyde (MDA), and reduced glutathione (GSH) levels in patients with overt hypothyroidism (OHT) and subclinical hypothyroidism (SHT) in comparison to euthyroid controls.

Subjects and methods

Albumin, IMA, IMA/albumin ratio, MDA, GSH, total cholesterol (TC), triglycerides (TG), HDL-Cholesterol were assessed in 105 subjects grouped into OHT, SHT patients, and euthyroid controls with 35 subjects in each group.

Results

MDA and IMA levels were significantly elevated while the GSH concentrations were significantly lower in OHT and SHT patients compared to controls (p < 0.01). When IMA values were normalized for albumin concentrations, the IMA/albumin ratio was also significantly elevated in both patient groups compared to controls (p < 0.01). These changes were more pronounced in the OHT group when compared to SHT group. In OHT group, thyroid-stimulating hormone (TSH) levels showed significant positive correlation with MDA (r = 0.470, p = 0.004), IMA (r = 0.530, p = 0.001), and IMA/albumin ratio (r = 0.525, p = 0.001). Both IMA (r = −0.342, p = 0.041), IMA/albumin ratio (r = −0.378, p = 0.023) showed significant negative correlation with GSH in OHT patients. No significant correlation between variables was, however, observed in SHT group.

Conclusions

Increase of MDA and IMA levels with decreased antioxidant status indicate the presence of OS in hypothyroid patients, which was more pronounced in OHT patients. Elevated levels of IMA can be a clinically useful marker of protein oxidative damage and OS in hypothyroidism.

Keywords

Oxidative stress Malondialdehyde Ischemia-modified albumin Glutathione Hypothyroidism 

Abbreviations

OS

Oxidative stress

OHT

Overt hypothyroidism

SHT

Subclinical hypothyroidism

MDA

Malondialdehyde

PCO

Protein carbonyls

IMA

Ischemia-modified albumin

HSA

Human serum albumin

ROS

Reactive oxygen species

GSH

Reduced glutathione

TSH

Thyroid-stimulating hormone

T3

Triiodothyronine

T4

Thyroxine

TC

Total cholesterol

DTT

Dithiothreitol

ABSU

Absorbance units

DTNB

Dithiobis-nitro benzoic acid

SD

Standard deviation

ANOVA

Analysis of variance

Notes

Conflict of interest

Authors declare that they have no conflict of interest.

Ethical approval

The present study was approved by the Institutional ethical committee.

Informed consent

The study was carried out on human participants after obtaining informed consent from the participants.

References

  1. 1.
    Nanda N, Bobby Z, Hamide A (2008) Association of thyroid stimulating hormone and coronary lipid risk factors with lipid peroxidation in hypothyroidism. Clin Chem Lab Med 46:674–679PubMedCrossRefGoogle Scholar
  2. 2.
    Torun AN, Kulaksizoglu S, Kulaksizoglu M et al (2009) Serum total antioxidant status and lipid peroxidation marker malondialdehyde levels in overt and subclinical hypothyroidism. Clin Endocrinol (Oxf) 70:469–474CrossRefGoogle Scholar
  3. 3.
    Santi A, Duarte MMMF, Moresco RN et al (2010) Association between thyroid hormones, lipids and oxidative stress biomarkers in overt hypothyroidism. Clin Chem Lab Med 48:1635–1639PubMedCrossRefGoogle Scholar
  4. 4.
    Kebapcilar L, Akinci B, Bayraktar F et al (2007) Plasma thiobarbituric acid-reactive substance levels in subclinical hypothyroidism. Med Princ Pract 16:432–436PubMedCrossRefGoogle Scholar
  5. 5.
    Duarte MMMF, Rocha JB, Moresco RN et al (2009) Association between ischemia-modified albumin, lipids and inflammation biomarkers in patients with hypercholesterolemia. Clin Biochem 42:666–671PubMedCrossRefGoogle Scholar
  6. 6.
    Sbarouni E, Georgiadou P, Voudris V (2011) Ischemia modified albumin changes-review and clinical implications. Clin Chem Lab Med 49:177–184PubMedCrossRefGoogle Scholar
  7. 7.
    Ivanov AI, Korolenko EA, Korolik EV et al (2002) Chronic liver and renal diseases differently affect structure of human serum albumin. Arch Biochem Biophys 408:69–77PubMedCrossRefGoogle Scholar
  8. 8.
    Kaefer M, Piva SJ, De Carvalho JA et al (2010) Association between ischemia modified albumin, inflammation and hyperglycemia in type 2 diabetes mellitus. Clin Biochem 43:450–454PubMedCrossRefGoogle Scholar
  9. 9.
    Bhagavan NV, Lai EM, Rios PA et al (2003) Evaluation of human serum albumin cobalt binding assay for the assessment of myocardial ischemia and myocardial infarction. Clin Chem 49:581–585PubMedCrossRefGoogle Scholar
  10. 10.
    Gaze DC (2009) Ischemia modified albumin: a novel biomarker for the detection of cardiac ischemia. Drug Metab Pharmacokinet 24:333–341PubMedCrossRefGoogle Scholar
  11. 11.
    Sharma R, Gaze DC, Pellerin D et al (2007) Evaluation of ischaemia-modified albumin as a marker of myocardial ischaemia in end-stage renal disease. Clin Sci (Lond) 113:25–32CrossRefGoogle Scholar
  12. 12.
    Jalan R, Schnurr K, Mookerjee RP et al (2009) Alterations in the functional capacity of albumin in patients with decompensated cirrhosis is associated with increased mortality. Hepatology 50:555–564PubMedCrossRefGoogle Scholar
  13. 13.
    Ma SG, Wei CL, Hong B et al (2011) Ischemia-modified albumin in type 2 diabetic patients with and without peripheral arterial disease. Clinics (Sao Paulo) 66:1677–1680Google Scholar
  14. 14.
    Turedi S, Gunduz A, Mentese A et al (2008) The value of ischemia-modified albumin compared with d-dimer in the diagnosis of pulmonary embolism. Respir Res 9:49PubMedCentralPubMedCrossRefGoogle Scholar
  15. 15.
    Haribabu A, Reddy VS, Pallavi Ch et al (2013) Evaluation of protein oxidation and its association with lipid peroxidation and thyrotropin levels in overt and subclinical hypothyroidism. Endocrine 44:152–157PubMedCrossRefGoogle Scholar
  16. 16.
    Reddy VS, Gouroju S, Suchitra MM et al (2013) Antioxidant defence in overt and subclinical hypothyroidism. Horm Metab Res 45:754–758PubMedCrossRefGoogle Scholar
  17. 17.
    Zurawska-Płaksej E, Grzebyk E, Marciniak D et al (2014) Oxidatively modified forms of albumin in patients with risk factors of metabolic syndrome. J Endocrinol Invest 37:819–827PubMedCentralPubMedCrossRefGoogle Scholar
  18. 18.
    Piva SJ, Duarte MM, Da Cruz IB et al (2011) Ischemia modified albumin as an oxidative stress biomarker in obesity. Clin Biochem 44:345–347PubMedCrossRefGoogle Scholar
  19. 19.
    Ma SG, Yang LX, Bai F et al (2012) Ischemia-modified albumin in patients with hyperthyroidism and hypothyroidism. Eur J Intern Med 23:e136–e140PubMedCrossRefGoogle Scholar
  20. 20.
    Ersoy K, Anaforoğlu İ, Algün E (2013) Serum ischemic modified albumin levels might not be a marker of oxidative stress in patients with hypothyroidism. Endocrine 43:430–433PubMedCrossRefGoogle Scholar
  21. 21.
    Nanda N, Bobby Z, Hamide A (2008) Oxidative stress and protein glycation in primary hypothyroidism. Male/female difference. Clin Exp Med 8:101–108PubMedCrossRefGoogle Scholar
  22. 22.
    Pasupathi P, Latha R (2008) Free radical activity and antioxidant defense mechanisms in patients with hypothyroidism. Thyroid Sci 3(12):CLS1–CLS6Google Scholar
  23. 23.
    Friedewald WT, Levy RI, Fredrickson DS (1972) Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without the use of preparative ultracentrifuge. Clin Chem 18:499–502PubMedGoogle Scholar
  24. 24.
    Sangeetha P, Das U, Koratkar R et al (1990) Increase in free radical generation and lipid peroxidation following chemotherapy in patients with cancer. Free Radic Biol Med 8:15–19PubMedCrossRefGoogle Scholar
  25. 25.
    Senes M, Kazan N, Coskun O et al (2007) Oxidative and nitrosative stress in acute ischaemic stroke. Ann Clin Biochem 44:43–47PubMedCrossRefGoogle Scholar
  26. 26.
    Ellman GL (1959) Tissue sulfhydryl groups. Arch Biochem Biophys 82:70–77PubMedCrossRefGoogle Scholar
  27. 27.
    Zhang YJ, Zhao W, Zhu MY et al (2013) Thyroid-stimulating hormone induces the secretion of tumor necrosis factor-α from 3T3-L1 adipocytes via a protein kinase A-dependent pathway. Exp Clin Endocrinol Diabetes 121:488–493PubMedCrossRefGoogle Scholar
  28. 28.
    Venditti P, Di Meo S (2006) Thyroid hormone-induced oxidative stress. Cell Mol Life Sci 63:414–434PubMedCrossRefGoogle Scholar
  29. 29.
    Oziol L, Faure P, Bertrand N et al (2003) Inhibition of vitro macrophage induced low density lipoprotein oxidation by thyroid compounds. J Endocrinol 177:137–146PubMedCrossRefGoogle Scholar
  30. 30.
    Resch U, Helsel G, Tatzber F et al (2002) Antioxidant status in thyroid dysfunction. Clin Chem Lab Med 40:1132–1134PubMedCrossRefGoogle Scholar
  31. 31.
    Dardano A, Ghiadoni L, Plantinga Y et al (2006) Recombinant human TSH reduces endothelium dependent vasodilation in patients monitored for differentiated thyroid carcinoma. J Clin Endocrinol Metab 91:4175–4178PubMedCrossRefGoogle Scholar
  32. 32.
    Varghese S, Shameena B, Oommen OV (2001) Thyroid hormones regulate lipid peroxidation and antioxidant enzyme activities in Anabas testudineus (Bloch). Comp Biochem Physiol 124B:185–192Google Scholar
  33. 33.
    Benov L (2001) How superoxide radical damages the cell. Protoplasma 217:33–36PubMedCrossRefGoogle Scholar
  34. 34.
    Ghosh S, Rahaman SO, Sarkar PK (1999) Regulation of neurofilament gene expression by thyroid hormone in the developing rat brain. NeuroReport 10:2361–2365PubMedCrossRefGoogle Scholar
  35. 35.
    Hakligör A, Kösem A, Seneş M et al (2010) Effect of albumin concentration and serum matrix on ischemia-modified albumin. Clin Biochem 43:345–348PubMedCrossRefGoogle Scholar
  36. 36.
    Lippi G, Montagnana M, Salvagno GL et al (2007) Standardization of ischemia-modified albumin testing: adjustment for serum albumin. Clin Chem Lab Med 45:261–262PubMedGoogle Scholar
  37. 37.
    Albarello K, Dos Santos GA, Bochi GV et al (2012) Ischemia modified albumin and carbonyl protein as potential biomarkers of protein oxidation in hemodialysis. Clin Biochem 45:450–454PubMedCrossRefGoogle Scholar
  38. 38.
    Porter NA (1984) Chemistry of lipid peroxidation. Methods Enzymol 105:273–282PubMedCrossRefGoogle Scholar
  39. 39.
    Grimsrud PA, Xie H, Griffin TJ et al (2008) Oxidative stress and covalent modification of protein with bioactive aldehydes. J Biol Chem 283:21837–21841PubMedCentralPubMedCrossRefGoogle Scholar
  40. 40.
    Mayes PA (1977) Metabolism of lipids. In: Harper HA, Rodwell VW, Mayes PA (eds) Review of physiological chemistry. Lange, California, pp 300–301Google Scholar
  41. 41.
    Bhagavan NV, Ha JS, Park JH et al (2009) Utility of serum fatty acid concentrations as a marker for acute myocardial infarction and their potential role in the formation of ischemia modified albumin: a pilot study. Clin Chem 55:1588–1590PubMedCrossRefGoogle Scholar

Copyright information

© Italian Society of Endocrinology (SIE) 2015

Authors and Affiliations

  • S. V. Reddy
    • 1
  • M. M. Suchitra
    • 1
  • V. Pradeep
    • 1
  • S. Alok
    • 1
  • V. Suresh
    • 1
  • A. R. Bitla
    • 1
  • P. V. L. N. Srinivasa Rao
    • 1
  1. 1.Sri Venkateswara Institute of Medical SciencesTirupatiIndia

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