Pediatric Cardiology

, Volume 39, Issue 4, pp 786–793 | Cite as

Determinants of Increased Aortic Diameters in Young Normotensive Patients With Turner Syndrome Without Structural Heart Disease

  • A. Uçar
  • Melike Tuğrul
  • Bülent Oğuz Erol
  • Ensar Yekeler
  • Banu Aydın
  • Seher Yıldız
  • Kemal Nişli
  • Firdevs Baş
  • Şükran Poyrazoğlu
  • Feyza Darendeliler
  • Nurçin Saka
  • Aylin Yetim Şahin
  • Yasin Yılmaz
  • Rüveyde Bundak
Original Article


Factors associated with aortic dilation and dissection in patients with Turner syndrome (TS) remain unclear. We assessed magnetic resonance imaging-based aortic diameters at nine predefined anatomic positions and examined associations of increased aortic diameters with B-type natriuretic peptide (BNP), A-type NP (ANP), growth hormone treatment, insulin-like growth factor 1 (IGF1), and estrogen status. Forty-seven patients with TS aged 7.3–21 years and 34 healthy peers were enrolled in this study. Aortic diameters were higher in patients with TS at three positions than in controls (p < 0.05). History of GH treatment, pubertal status, and serum estradiol levels were not associated with increased aortic diameters. Patients with TS had higher plasma BNP and ANP levels than controls. BNP and IGF1 were independently associated with the increase in aortic diameters in TS at three positions of the ascending aorta (R2 = 0.361–0.458, p < 0.05 for all). At two positions of the descending aorta, only BNP emerged as an independent variable (R2 = 0.130–0.139, p < 0.05). We conclude that young, normotensive patients with TS had greater aortic diameters at several positions than healthy controls. BNP and IGF1 were independently associated with increased aortic diameters in TS.


Turner syndrome Aortic diameters B-natriuretic peptide Insulin-like growth factor 1 



We thank all the patients and controls who participated in this study. We also thank Mr. David Chapman for editing this manuscript.


This project was partially funded by Scientific Research Projects Coordination Unit of Istanbul University. Grant Number: 39521.

Compliance with Ethical Standards

Conflict of interest

No potential conflict of interest exists with this research, and no sponsors were involved.

Ethical Approval

All procedures were performed in accordance with the ethical standards of the institutional research committee and with 1964 Helsinki declaration or comparable ethical standards.


  1. 1.
    Stochholm K, Juul S, Juel K, Naeraa RW, Gravholt CH (2006) Prevalence, incidence, diagnostic delay, and mortality in Turner syndrome. J Clin Endocrinol Metab 91:3897–3902CrossRefPubMedGoogle Scholar
  2. 2.
    Natwani NC, Unwin R, Brook CG, Hindmarsh PC (2000) The influence of renal and cardiovascular abnormalities on blood pressure in Turner syndrome. Clin Endocrinol 52:371–377CrossRefGoogle Scholar
  3. 3.
    Gravholt CH, Hansen KW, Erlandsen M, Ebbehøj E, Christiansen JS (2006) Nocturnal hypertension and impaired sympathovagal tone in Turner syndrome. J Hypertens 24:353–360CrossRefPubMedGoogle Scholar
  4. 4.
    Ross JL, Feuillan P, Long LM, Kowal K, Kushner H, Cutler GB Jr (1995) Lipid abnormalities in Turner syndrome. J Pediatr 126:242–245CrossRefPubMedGoogle Scholar
  5. 5.
    Mortensen KH, Andersen NH, Gravholt CH (2012) Cardiovascular phenotype in Turner syndrome—integrating cardiology, genetics, and endocrinology. Endocr Rev 33:677–714CrossRefPubMedGoogle Scholar
  6. 6.
    Subramaniam DR, Stoddard WA, Mortensen KH, Ringgaard S, Trolle C, Gravholt CH (2017) Continuous measurements of aortic dimensions in Turner syndrome: a cardiovascular magnetic resonance study. J Cardiovasc Magn Reson 19(1):20. CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Mortensen KH, Erlandsen M, Andersen NH, Gravholt CH (2013) Prediction of aortic dilation in Turner syndrome—the use of serial cardiovascular magnetic resonance. J Cardiovasc Magn Reson 15:47CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Mavinkurve M, O’Gorman Clodagh S (2017) Can brain natriuretic peptides and osteoprotegerin serve as biochemical markers for the detection of aortic pathology in children and adolescents with Turner syndrome? Front Endocrinol 8:142. CrossRefGoogle Scholar
  9. 9.
    Quezada E, Lapidus J, Shaughnessy R, Chen Z, Silberbach M (2015) Aortic dimensions in Turner syndrome. Am J Med Genet Part A 167A:2527–2532CrossRefPubMedGoogle Scholar
  10. 10.
    Gutin LS, Bakalov VK, Douglas R, Rosing DR, Arai AE, Gharib AM, Bondy CA (2012) N-terminal pro-brain natriuretic peptide levels and aortic diameters. Am Heart J 164:419–424CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Castillo C, Cruzado M, Ariznavarreta C, Gil-Loyzaga P, Lahera V, Cachofeiro V, Tresguerres JA (2005) Effect of recombinant growth hormone administration on body composition and vascular function and structure in old male Wistar rats. Biogerontology 6:303–312CrossRefPubMedGoogle Scholar
  12. 12.
    Stochholm K, Laursen T, Green A, Laurberg P, Andersen M, Kristensen L, Feldt-Rasmussen U, Christiansen JS, Frydenberg M, Gravholt CH (2008) Morbidity and GH deficiency: a nationwide study. Eur J Endocrinol 158:447–457CrossRefPubMedGoogle Scholar
  13. 13.
    Bengtsson BA, Edén S, Ernest I, Odén A, Sjögren B (1988) Epidemiology and long-term survival in acromegaly. A study of 166 cases diagnosed between 1955 and 1984. Acta Med Scand 223:327–335CrossRefPubMedGoogle Scholar
  14. 14.
    Matura LA, Sachdev V, Bakalov VK, Rosing DR, Bondy CA (2007) Growth hormone treatment and left ventricular dimensions in Turner syndrome. J Pediatr 150:587–591CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Van den Berg J, Bannink EM, Wielopolski PA, Hop WC, van Osch-Gevers L, Pattynama PM, de M Keizer-Schrama, Helbing SM WA (2008) Cardiac status after childhood growth hormone treatment of Turner syndrome. J Clin Endocrinol Metab 93:2553–2558CrossRefPubMedGoogle Scholar
  16. 16.
    Uçar A, Oz F, Bas F, Oflaz H, Nişli K, Tuğrul M, Yetim A, Darendeliler F, Saka N, Poyrazoğlu Ş, Bundak R (2015) Increased arterial stiffness in young normotensive patients with Turner syndrome: associations with vascular biomarkers. Clin Endocrinol 82:719–727CrossRefGoogle Scholar
  17. 17.
    Guven B, Can M, Mungan G, Acіkgoz S (2013) Reference values for serum levels of insulin-like growth factor 1 (IGF-1) and IGF-binding protein 3 (IGFBP-3) in the West Black Sea region of Turkey. Scand J Clin Lab Invest 73(2):135–140CrossRefPubMedGoogle Scholar
  18. 18.
    Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC (1985) Homeostasis model assessment: insulin resistance and b-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 28:412–419CrossRefPubMedGoogle Scholar
  19. 19.
    Keskin M, Kurtoglu S, Kendirci M, Atabek ME, Yazici C (2005) Homeostasis model assessment is more reliable than the fasting glucose/insulin ratio and quantitative insulin sensitivity check index for assessing insulin resistance among obese children and adolescents. Pediatrics 115:e500–e503CrossRefPubMedGoogle Scholar
  20. 20.
    Zimmet P, Alberti KG, Kaufman F, Tajima N, Silink M, Arslanian S, Wong G, Bennett P, Shaw J, Caprio S, IDF Consensus Group (2007) The metabolic syndrome in children and adolescents–an IDF consensus report. Pediatr Diab 8, 299–306CrossRefGoogle Scholar
  21. 21.
    Urbina E, Alpert B, Flynn J et al (2008) Ambulatory blood pressure monitoring in children and adolescents: recommendations for standard assessment: a scientific statement from the American Heart Association Atherosclerosis, Hypertension, and Obesity in Youth Committee of the Council on Cardiovascular Disease in the Young and the Council for High Blood Pressure Research. Hypertension 52:433–444CrossRefPubMedGoogle Scholar
  22. 22.
    Verdecchia P, Schillaci G, Guerrieri M et al (1990) Circadian blood pressure changes and left ventricular hypertrophy in essential hypertension. Circulation 81:528–536CrossRefPubMedGoogle Scholar
  23. 23.
    Haycock GB, Schwartz GJ, Wisotsky DH (1978) Geometric method for measuring body surface area: a height-weight formula validated in infants, children, and adults. J Pediatr 93(1):62–66CrossRefPubMedGoogle Scholar
  24. 24.
    Mahabala C, Kamath P, Bhaskaran U, Pai ND, Pai AU (2013) Antihypertensive therapy: nocturnal dippers and nondippers. Do we treat them differently? Vasc Health Risk Manag 9:125–133CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Sas TC, de Muinck Keizer-Schrama SM, Stijnen T, Aanstoot HJ, Drop SL (2000) Carbohydrate metabolism during long-term growth hormone (GH) treatment and after discontinuation of GH treatment in girls with Turner syndrome participating in a randomized dose-response study. Dutch Advisory Group on Growth Hormone. J Clin Endocrinol Metab 85:769–775PubMedGoogle Scholar
  26. 26.
    Van den Berg J, Bannink EM, Wielopolski PA, Pattynama PM, de Muinck Keizer-Shrama SM, Helbing WA (2006) Aortic distensibility and dimensions and the effects of growth hormone treatment in the Turner syndrome. Am J Cardiol 97:1644–1649CrossRefPubMedGoogle Scholar
  27. 27.
    Bolar K, Hoffman AR, Maneatis T, Lippe B (2008) Long term safety of recombinant human growth hormone in Turner syndrome. J Clin Endocrinol Metab 93:344–351CrossRefPubMedGoogle Scholar
  28. 28.
    Bondy CA, Van PL, Bakalov VK, Ho VB (2006) Growth hormone treatment and aortic dimensions in Turner syndrome. J Clin Endocrinol Metab 91:1785–1788CrossRefPubMedGoogle Scholar
  29. 29.
    Ungvari Z, Gautam T, Koncz P, Henthorn JC, Pinto JT, Ballabh P, Yan H, Mitschelen M, Farley J, Sonntag WE, Csiszar A (2010) Vasoprotective effects of life span-extending peripubertal GH replacement in Lewis dwarf rats. J Gerontol A 65:1145–1156CrossRefGoogle Scholar
  30. 30.
    Ungvari Z, Sosnowska D, Podlutsky A, Koncz P, Sonntag WE, Csiszar A (2011) Free radical production, antioxidant capacity, and oxidative stress response signatures in fibroblasts from Lewis dwarf rats: effects of life span extending peripubertal GH treatment. J Gerontol A 66:501–510CrossRefGoogle Scholar
  31. 31.
    Baronio F, Mazzanti L, Girtler Y, Tamburrino F, Longhi LupiF, Fanolla S, Radetti A G (2017) The influence of GH treatment on glucose homeostasis in girls with Turner syndrome: a 7-year study. J Clin Endocrinol Metab 102(3):878–883. PubMedGoogle Scholar
  32. 32.
    Castillo C, Cruzado M, Ariznavarreta C, Gil-Loyzaga P, Lahera V, Cachofeiro V, Tresguerres JA (2005) Effect of recombinant human growth hormone administration on body composition and vascular function and structure in old male Wistar rats. Biogerontology 6:303–312CrossRefPubMedGoogle Scholar
  33. 33.
    Lombardi G, Galdiero M, Auriemma RS, Pivonello R, Colao A (2006) Acromegaly and the cardiovascular system. Neuroendocrinology 83:211–217CrossRefPubMedGoogle Scholar
  34. 34.
    Cintron D, Rodriguez-Gutierrez R, Serrano V, Latortue-Albino P, Erwin PJ, Murad MH (2017) Effect of estrogen replacement therapy on bone and cardiovascular outcomes in women with Turner syndrome: a systematic review and meta-analysis. Endocrine 55(2):366–375CrossRefPubMedGoogle Scholar
  35. 35.
    Lazo M, Young JH, Brancati LF, Coresh J, Whelton S, Ndumele CE, Hoogeveen R, Ballantyne CM, Selvin E (2013) NH2-terminal pro-brain natriuretic peptide and risk of diabetes. Diabetes 62:3189–3193CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Wang TJ, Larson MG, Levy D, Benjamin EJ, Leip EP, Omland T, Wolf PA, Vasan RS (2004) Plasma natriuretic peptide levels and the risk of cardiovascular events and death. N Engl J Med 350:655–663CrossRefPubMedGoogle Scholar
  37. 37.
    Habashi JP, Judge DP, Holm TM, Cohn RD, Loeys BL, Cooper TK, Myers L, Klein EC, Liu G, Calvi C, Podowski M, Neptune ER, Halushka MK, Bedja D, Gabrielson K, Rifkin DB, Carta L, Ramirez F, Huso DL, Dietz HC (2006) Losartan, an AT1 antagonist, prevents aortic aneurysm in a mouse model of Marfan syndrome. Science 312(5770):117–121CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • A. Uçar
    • 1
    • 5
  • Melike Tuğrul
    • 1
  • Bülent Oğuz Erol
    • 4
  • Ensar Yekeler
    • 4
  • Banu Aydın
    • 1
  • Seher Yıldız
    • 1
  • Kemal Nişli
    • 3
  • Firdevs Baş
    • 1
  • Şükran Poyrazoğlu
    • 1
  • Feyza Darendeliler
    • 1
  • Nurçin Saka
    • 1
  • Aylin Yetim Şahin
    • 2
  • Yasin Yılmaz
    • 1
  • Rüveyde Bundak
    • 1
  1. 1.Department of Pediatric Endocrinology and Diabetes, Faculty of MedicineIstanbul UniversityIstanbulTurkey
  2. 2.Department of Adolescent Medicine, Faculty of MedicineIstanbul UniversityIstanbulTurkey
  3. 3.Department of Pediatric Cardiology, Faculty of MedicineIstanbul UniversityIstanbulTurkey
  4. 4.Department of Pediatric Radiology, Faculty of MedicineIstanbul UniversityIstanbulTurkey
  5. 5.Pediatric Endocrinology & Diabetes Outpatient Clinic, Şişli Hamidiye Etfal Education & Research HospitalUniversity of Health SciencesŞişli, IstanbulTurkey

Personalised recommendations