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Endocrine

pp 1–7 | Cite as

Evaluation of cardiovascular risk by growth-differentiation factor-15 and tissue Doppler imaging in children with subclinical hypothyroidism

  • Derya ArslanEmail author
  • Muammer Buyukinan
  • Celil Uysal
  • Cigdem Damla Deniz
Original Article

Abstract

Objective

Subclinical hypothyroidism, defined as increased TSH serum levels and normal serum free T4 concentrations, has been associated with an increased risk of heart disease in adults. But, data in children and adolescents are scanty and treatment of subclinical hypothyroidism is controversial. Growth differentiation factor-15 (GDF-15) is a promising biomarker of cardiac remodeling. This study aimed to evaluate the cardiovascular risk factors in children with subclinical hypothyroidism, measured with tissue Doppler echocardiography (TDE), and conventional echocardiography and GDF-15 level.

Methods

The study comprised a total of 41 pediatric patients with subclinical hypothyroidism (SH) (mean age 9.6 ± 4.7 years) and 31 healthy children (mean age 11.2 ± 3.4 years) as the control group. Subclinical hypothyroidism was defined as a thyroid-stimulating hormone level higher than 4 mIU/l and a normal free-thyroxine level (0.6–1.8 ng/dl). Tissue Doppler echocardiography was performed to all individuals in the control group and patient group at the beginning of the study. Global systolic function as assessed by left ventricular ejection fraction was compared between groups. The serum GDF-15 level was measured.

Results

There were no significant differences in demographic parameters between the SH and control groups. The left ventricular internal diameter end systole, interventricular septal end diastole, left ventricular posterior wall end diastole, and tricuspid annular plane systolic excursion values were significantly different between the SH and control groups (p = 0.038, 0.028, 0.005, and 0.000, respectively). The mean mitral isovolumic relaxation time value of the SH group was 57.2 ± 9.3 ms, compared to 44.5 ± 5.6 ms for the control group (p = 0.000). The mean tricuspid isovolumic contraction time value of the SH group was 58.7 ± 9.4 ms, and that of the control group was 45.1 ± 5.3 ms (p = 0.000). The mean tricuspid isovolumic relaxation time value of the SH group was 58.03 ± 9.5 ms, and that of the control group was 45.1 ± 5.3 ms (p = 0.000). There were no significant differences in the other m-mode or pulse Doppler echocardiography values between two groups. The GDF-15 value of the SH group was 382.6 ± 268.2 pg/mL, and that of the control group was 473.6 ± 337.9 pg/mL; this difference was not significant.

Conclusion

Patients with subclinical hypothyroidism versus healthy individuals had some changes in echocardiographic parameters that indicate involvement of diastolic function of the left ventricle. They were significantly different when compared SH group and the control group. This study demonstrated ventricle diastolic dysfunction in pediatric patients with hypothyroidism. The results of our study suggest that cardiac follow-up may be useful in patients with subclinical hypothyroidism and clinical trials are needed to explore therapeutic effects of T4 and T3 administration in this patients.

Keywords

Subclinical hypothyroidism Cardiovascular risk GDF-15 Child 

Notes

Acknowledgements

The authors thank the children and parents at the participating study.

Funding

This work was funded by University of Health Sciences Konya Training and Research Hospital Medical Board of Education.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

The study was approved by the Ethics Committee of Necmettin Erbakan University Meram Medical Faculty. All procedures performed in studies involving human participants were in accordance with the ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

References

  1. 1.
    Y. Yadav, U.K. Saikia, D. Sarma, M. Hazarika, Cardiovascular risk factors in children and adolescents with subclinical hypothyroidism. Indian J. Endocrinol. Metab. 21(6), 823–829 (2017)CrossRefGoogle Scholar
  2. 2.
    X. Quan, Y. Ji, C. Zhang, X. Guo, Y. Zhang, S. Jia, W. Ma, Y. Fan, C. Wang, Circulating MiR-146a may be a potential biomarker of coronary heart disease in patients with subclinical hypothyroidism. Cell. Physiol. Biochem. 45(1), 226–236 (2018)CrossRefGoogle Scholar
  3. 3.
    T. Wu, J.W. Flowers, F. Tudiver, J.L. Wilson, N. Punyasavatsut, Subclinical thyroid disorders and cognitive performance among adolescents in the United States. BMC Paediatr. 6, 12 (2006)CrossRefGoogle Scholar
  4. 4.
    M. Salerno, D. Capalbo, M. Cerbone, F. De Luca, Subclinical hypothyroidism in childhood - current knowledge and open issues. Nat. Rev. Endocrinol. 12(12), 734–746 (2016)CrossRefGoogle Scholar
  5. 5.
    A. Altamirano Ufion, B. Zulfiqar, A. Hassan, R. Habibi, P. Boddu, Subclinical hypothyroidism and its association with increased cardiovascular mortality. Cardiol. Res. Pract. 2017, 7539735 (2017).  https://doi.org/10.1155/2017/7539735. CrossRefGoogle Scholar
  6. 6.
    D.K. Rohrer, R. Hartong, W.H. Dillmann, Influence of thyroid hormone and retinoic acid on slow sarcoplasmic reticulum Ca2+ ATPase and myosin heavy chain α gene expression in cardiac myocytes: delineation of cis-active DNA elements that confer responsiveness to thyroid hormone but not to retinoic acid. J. Biol. Chem. 266(13), 8638–8646 (1991)Google Scholar
  7. 7.
    N. Rodondi, A.B. Newman, E. Vittinghoff, N. de Rekeneire, S. Satterfield, T.B. Harris, D.C. Bauer, Subclinical hypothyroidism and the risk of heart failure, other cardiovascular events, and death. Arch. Int Med. 165(21), 2460–2466 (2005)CrossRefGoogle Scholar
  8. 8.
    A. Sharma, S.R. Stevens, J. Lucas, M. Fiuzat, K.F. Adams, D.J. Whellan, M.P. Donahue, D.W. Kitzman, I.L. Piña, F. Zannad, W.E. Kraus, C.M. O’Connor, G.M. Felker, Utility of growth differentiation factor-15, a marker of oxidative stress and inflammation, in chronic heart failure: insights from the HF-ACTION study. JACC Heart Fail. 5(10), 724–734 (2017)CrossRefGoogle Scholar
  9. 9.
    R.M. Lang, M. Bierig, R.B. Devereux, F.A. Flachskampf, E. Foster, P.A. Pellikka, M.H. Picard, M.J. Roman, J. Seward, J.S. Shanewise, S.D. Solomon, K.T. Spencer, M.S. Sutton, W.J. Stewart, Recommendations for chamber quantification: a report from the American Society of Echocardiography’s Guidelines and Standards Committee and the Chamber Quantification Writing Group, developed in conjunction with the European Association of Echocardiography, a branch of the European Society of Cardiology. J. Am. Soc. Echocardiogr. 18(12), 1440–1463 (2005)CrossRefGoogle Scholar
  10. 10.
    M.I. Surks, E. Ortiz, G.H. Daniels, C.T. Sawin, N.F. Col, R.H. Cobin, J.A. Franklyn, J.M. Hershman, K.D. Burman, M.A. Denke, C. Gorman, R.S. Cooper, N.J. Weissman, Subclinical thyroid disease: scientific review and guidelines for diagnosis and management. JAMA 291, 228–238 (2004)CrossRefGoogle Scholar
  11. 11.
    M. Cojić, L. Cvejanov-Kezunović, Subclinical hypothyroidism—whether and when to start treatment? Open Access Maced. J. Med. Sci. 5(7), 1042–1046 (2017)Google Scholar
  12. 12.
    M.D. Cheitlin, W.F. Armstrong, G.P. Aurigemma, G.A. Beller, F.Z. Bierman, J.L. Davis, P.S. Douglas, D.P. Faxon, L.D. Gillam, T.R. Kimball, W.G. Kussmaul, A.S. Pearlman, J.T. Philbrick, H. Rakowski, D.M. Thys, ACC/AHA/ASE 2003 guideline update for the clinical application of echocardiography--summary article: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (ACC/AHA/ASE Committee to Update the 1997 Guidelines for the Clinical Application of Echocardiography). J. Am. Coll. Cardiol. 42(5), 954–970 (2003)CrossRefGoogle Scholar
  13. 13.
    N.B. Schiller, Two-dimensional echocardiographic determination of left ventricular volume, systolic function, and mass. Summary and discussion of the 1989 recommendations of the American Society of Echocardiography. Circulation 84(3), 1280–1287 (1991)Google Scholar
  14. 14.
    E. Schmid, J.N. Hilberath, G. Blumenstock, P.S. Shekar, S. Kling, S.K. Shernan, P. Rosenberger, M. Nowak-Machen, Tricuspid annular plane systolic excursion (TAPSE) predicts poor outcome in patients undergoing acute pulmonary embolectomy. Heart Lung Vessels 7(2), 151–158 (2015)Google Scholar
  15. 15.
    R. Gallizzi, C. Crisafulli, T. Aversa, G. Salzano, F. De Luca, M. Valenzise, G. Zirilli, Subclinical hypothyroidism in children: is it always subclinical? Ital. J. Pedia. 44(1), 25 (2018)CrossRefGoogle Scholar
  16. 16.
    S.H. Pearce, G. Brabant, L.H. Duntas, F. Monzani, R.P. Peeters, S. Razvi, J.L. Wemeau, ETA guideline: management of subclinical hypothyroidism. Eur. Thyroid J. 2(4), 215–228 (2013)CrossRefGoogle Scholar
  17. 17.
    J.R. Garber, R.H. Cobin, H. Gharib, J.V. Hennessey, I. Klein, J.I. Mechanick, R. Pessah-Pollack, P.A. Singer, K.A. Woeber, Clinical practice guidelines for hypothyroidism in adults: cosponsored by the American Association of Clinical Endocrinologists and the American Thyroid Association. Thyroid 22(12), 1200–1235 (2012)CrossRefGoogle Scholar
  18. 18.
    L.H. Duntas, L. Wartofsky, Cardiovascular risk and subclinical hypothyroidism: Focus on lipids and new emerging risk factors. What is the evidence? Thyroid 17(11), 1075–1084 (2007)CrossRefGoogle Scholar
  19. 19.
    A. Irdem, D. Aydın Sahin, M. Kervancioglu, O. Baspinar, M. Sucu, M. Keskin, M. Kilinc, Evaluation of P-wave dispersion, diastolic function, and atrial electromechanical conduction in pediatric patients with subclinical hypothyroidism. Echocardiography 33(9), 1397–1401 (2016)CrossRefGoogle Scholar
  20. 20.
    F. Franzoni, F. Galetta, P. Fallahi, L. Tocchini, G. Merico, L. Braccini, M. Rossi, A. Carpi, A. Antonelli, G. Santoro, Effect of L-thyroxine treatment on left ventricular function in subclinical hypothyroidism. Biomed. Pharmacother. 60(8), 431–436 (2006)CrossRefGoogle Scholar
  21. 21.
    F. Monzani, V. Di Bello, N. Caraccio, A. Bertini, D. Giorgi, C. Giusti, E. Ferrannini, Effect of levothyroxine on cardiac function and structure in subclinical hypothyroidism: a double blind, placebo-controlled Study. J. Clin. Endocrinol. Metab. 86, 1110–1115 (2001)CrossRefGoogle Scholar
  22. 22.
    T.K. Mishra, S.N. Routray, S. Das, M. Behera, Left ventricular dysfunction in patients with subclinical hypothyroidism and its reversibility after hormone therapy. J. Assoc. Physicians India 53, 943–946 (2005)Google Scholar
  23. 23.
    M.C. Vigone, D. Capalbo, G. Weber, M. Salerno, Mild hypothyroidism in childhood: who, when, and how should be treated? J. Endocr. Soc. 2(9), 1024–1039 (2018)Google Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Derya Arslan
    • 1
    Email author
  • Muammer Buyukinan
    • 2
  • Celil Uysal
    • 3
  • Cigdem Damla Deniz
    • 4
  1. 1.Department of Pediatric Cardiology, University of Health SciencesKonya Training and Research HospitalKonyaTurkey
  2. 2.Department of Pediatric EndocrinologyKonya Training and Research HospitalKonyaTurkey
  3. 3.Department of PediatricsPatnos State HospitalAgriTurkey
  4. 4.Department of BiochemistryKonya Training and Research HospitalKonyaTurkey

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