, Volume 65, Issue 3, pp 601–607 | 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



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.


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.


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.


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.


Subclinical hypothyroidism Cardiovascular risk GDF-15 Child 



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


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.


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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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