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Subclinical Hypothyroidism as a Risk Factor for the Development of Cardiovascular Disease in Obese Adolescents With Nonalcoholic Fatty Liver Disease

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Abstract

No data are available on the relationship between subclinical hypothyroidism and risk factors for the development of cardiovascular disease in obese adolescents with nonalcoholic fatty liver disease (NAFLD). This study aimed to determine whether an association exists between subclinical hypothyroidism and risk factors for the development of cardiovascular disease in obese adolescents with NAFLD. The study enrolled 111 obese adolescents and 42 lean subjects. The obese subjects were divided into two subgroups based on the presence or absence of fatty liver with high transaminases: a NAFLD group and a non-NAFLD group. Subclinical hypothyroidism was defined as a thyroid-stimulating hormone (TSH) level higher than 4 mIU/l and a normal free-thyroxine level (0.6–1.8 ng/dl). Insulin resistance was calculated by the homeostasis model assessment (HOMA-IR). Left ventricular mass (LVM), LVM index measurements, carotid intima media thickness (IMT), and HOMA-IR values were higher in the NAFLD obese group with TSH levels higher than 4 mIU/l than in the NAFLD obese group with TSH levels lower than 4 mIU/l. Elevated TSH values in the NAFLD obese group were positively correlated with most of the metabolic and cardiovascular risk parameters such as total cholesterol (r = 0.606, p = 0.001), triglycerides (r = 0.476, p = 0.016), low-density lipoprotein cholesterol (r = 0.461, p = 0.004), insulin (r = 0.607, p = 0.001), HOMA-IR (r = 0.596, p = 0.002), carotid IMT (r = 0.894, p < 0.0001), and LVM (r = 0.563, p = 0.003). The findings demonstrated that the obese adolescents with NAFLD and subclinical hypothyroidism had a more adverse cardiovascular risk profile and a higher carotid IMT and LVM.

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References

  1. Aeberli I, Jung A, Murer SB, Wildhaber J, Wildhaber-Brooks J, Knöpfli BH, Zimmermann MB (2010) During rapid weight loss in obese children, reductions in TSH predict improvements in insulin sensitivity independent of changes in body weight or fat. J Clin Endocrinol Metab 95:5412–5418

    Article  PubMed  CAS  Google Scholar 

  2. Alisi A, Manco M, Vania A, Nobili V (2009) Pediatric nonalcoholic fatty liver disease in 2009. J Pediatr 155:469–474

    Article  PubMed  Google Scholar 

  3. Biondi B, Fazio S, Palmieri A, Carella C, Panza N, Cittadini A, Bonè F, Lombardi G, Saccà L (1999) Left ventricular diastolic dysfunction in patients with subclinical hypothyroidism. J Clin Endocrinol Metab 84:2064–2067

    Article  PubMed  CAS  Google Scholar 

  4. Bluemke DA, Kronmal RA, Lima JA, Liu K, Olson J, Burke GL, Folsom AR (2008) The relationship of left ventricular mass and geometry to incident cardiovascular events: the MESA (multi-ethnic study of atherosclerosis) study. J Am Coll Cardiol 52:2148–2155

    Article  PubMed  Google Scholar 

  5. Carulli L, Ballestri S, Lonardo A, Lami F, Violi E, Losi L, Bonilauri L, Verrone AM, Odoardi MR, Scaglioni F, Bertolotti M, Loria P (2011) Is nonalcoholic steatohepatitis associated with a high-though-normal thyroid stimulating hormone level and lower cholesterol levels? Intern Emerg Med. Epub ahead of print 11 May 2011

  6. Dean JW, Fowler PB (1985) Exaggerated responsiveness to thyrotropin-releasing hormone: a risk factor in women with coronary artery disease. Br Med J 290:1555–1561

    Article  CAS  Google Scholar 

  7. Devereux RB, Alonso DR, Lutas EM, Gottlieb GJ, Campo E, Sachs I, Reichek N (1986) Echocardiographic assessment of left ventricular hypertrophy: comparison to necropsy findings. Am J Cardiol 57:450–458

    Article  PubMed  CAS  Google Scholar 

  8. Dörr M, Wolff B, Robinson DM, John U, Lüdemann J, Meng W, Felix SB, Völzke H (2005) The association of thyroid function with cardiac mass and left ventricular hypertrophy. J Clin Endocrinol Metab 90:673–677

    Article  PubMed  Google Scholar 

  9. Eckel RH, Grundy SM, Zimmet PZ (2005) The metabolic syndrome. Lancet 365:1415–1428

    Article  PubMed  CAS  Google Scholar 

  10. Hak AE, Pols HA, Visser T, Drexhage HA, Hofman A, Witteman JC (2000) Subclinical hypothyroidism is an independent risk factor for atherosclerosis and myocardial infarction in elderly women: the Rotterdam study. Ann Intern Med 132:270–278

    Article  PubMed  CAS  Google Scholar 

  11. Hollowell JG, Staehling NW, Flanders WD, Hannon WH, Gunter EW, Spencer CA, Braverman LE (2002) Serum TSH, T(4), and thyroid antibodies in the United States population (1988–1994): National health and nutrition examination survey (NHANES III). J Clin Endocrinol Metab 87:489–499

    Article  PubMed  CAS  Google Scholar 

  12. Iqbal A, Schirmer H, Lunde P, Figenschau Y, Rasmussen K, Jorde R (2007) Thyroid-stimulating hormone and left ventricular function. J Clin Endocrinol Metab 92:3504–3510

    Article  PubMed  CAS  Google Scholar 

  13. 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 115:500–503

    Article  Google Scholar 

  14. Kim SK, Kim SH, Park KS, Park SW, Cho YW (2009) Regression of the increased common carotid artery-intima media thickness in subclinical hypothyroidism after thyroid hormone replacement. Endocr J 56:753–758

    Article  PubMed  CAS  Google Scholar 

  15. Li X, Li S, Ulusoy E, Chen W, Srinivasan SR, Berenson GS (2004) Childhood adiposity as a predictor of cardiac mass in adulthood: the Bogalusa heart study. Circulation 110:3488–3492

    Article  PubMed  Google Scholar 

  16. Liangpunsakul S, Chalasani N (2003) Is hypothyroidism a risk factor for nonalcoholic steatohepatitis? J Clin Gastroenterol 37:340–343

    Article  PubMed  Google Scholar 

  17. Litwin M, Niemirska A (2009) Intima-media thickness measurements in children with cardiovascular risk factors. Pediatr Nephrol 24:707–719

    Article  PubMed  Google Scholar 

  18. Manco M, Bottazzo G, DeVito R, Marcellini M, Mingrone G, Nobili V (2008) Nonalcoholic fatty liver disease in children. J Am Coll Nutr 27:667–676

    PubMed  CAS  Google Scholar 

  19. Maratou E, Hadjidakis DJ, Kollias A, Tsegka K, Peppa M, Alevizaki M, Mitrou P, Lambadiari V, Boutati E, Nikzas D, Tountas N, Economopoulos T, Raptis SA, Dimitriadis G (2009) Studies of insulin resistance in patients with clinical and subclinical hypothyroidism. Eur J Endocrinol 160:785–790

    Article  PubMed  CAS  Google Scholar 

  20. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC (1985) Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in men. Diabetologia 28:412–429

    Article  PubMed  CAS  Google Scholar 

  21. Monzani F, Di Bello V, Caraccio N, Bertini A, Giorgi D, Giusti C, Ferrannini E (2001) Effect of levothyroxine on cardiac function and structure in subclinical hypothyroidism: a double-blind, placebo-controlled study. J Clin Endocrinol Metab 86:1110–1115

    Article  PubMed  CAS  Google Scholar 

  22. Monzani F, Caraccio N, Kozàkowà M, Dardano A, Vittone F, Virdis A, Taddei S, Palombo C, Ferrannini E (2004) Effect of levothyroxine replacement on lipid profile and intima-media thickness in subclinical hypothyroidism: a double-blind, placebo-controlled study. J Clin Endocrinol Metab 89:2099–2106

    Article  PubMed  CAS  Google Scholar 

  23. Ozturk A, Mazicioglu MM, Hatipoglu N, Budak N, Keskin G, Yazlak Z, Balci N, Yildiz H, Yildiz K, Ustunbas HB, Kurtoglu S (2008) Reference body mass index curves for Turkish children 6 to 18 years of age. J Pediatr Endocrinol Metab 21:827–836

    Article  PubMed  Google Scholar 

  24. Pacifico L, Nobili V, Anania C, Verdecchia P, Chiesa C (2011) Pediatric nonalcoholic fatty liver disease, metabolic syndrome and cardiovascular risk. World J Gastroenterol 17:3082–3091

    Article  PubMed  Google Scholar 

  25. Pacifico L, Anania C, Ferraro F, Andreoli GM, Chiesa C (2012) Thyroid function in childhood obesity and metabolic comorbidity. Clin Chim Acta 413:396–405

    Article  PubMed  CAS  Google Scholar 

  26. Paoli-Valeri M, Guzmán M, Jiménez-López V, Arias-Ferreira A, Briceño-Fernández M, Arata-Bellabarba G (2005) Atherogenic lipid profile in children with subclinical hypothyroidism. An Pediatr 62:128–134

    Article  CAS  Google Scholar 

  27. Pearce EN, Yang Q, Benjamin EJ, Aragam J, Vasan RS (2010) Thyroid function and left ventricular structure and function in the Framingham heart study. Thyroid 20:369–373

    Article  PubMed  CAS  Google Scholar 

  28. Rodondi N, Newman AB, Vittinghoff E, de Rekeneire N, Satterfield S, Harris TB, Bauer DC (2005) Subclinical hypothyroidism and the risk of heart failure, other cardiovascular events, and death. Arch Intern Med 165:2460–2466

    Article  PubMed  Google Scholar 

  29. Rodondi N, Bauer DC, Cappola AR, Cornuz J, Robbins J, Fried LP, Ladenson PW, Vittinghoff E, Gottdiener JS, Newman AB (2008) Subclinical thyroid dysfunction, cardiac function, and the risk of heart failure. The cardiovascular health study. J Am Coll Cardiol 52:1152–1159

    Article  PubMed  CAS  Google Scholar 

  30. Simon A, Megnien JL, Chironi G (2010) The value of carotid intima-media thickness for predicting cardiovascular risk. Arterioscler Thromb Vasc Biol 30:182–185

    Article  PubMed  CAS  Google Scholar 

  31. Squizzato A, Gerdes VEA, Brandjes DPM, Büller HR, Stam J (2005) Thyroid diseases and cerebrovascular disease. Stroke 36:2302–2310

    Article  PubMed  CAS  Google Scholar 

  32. Stephen CH, Tri HL, Stacey MA (2002) Nonalcoholic steatohepatitis. In: Sciff’s disease of the liver, 9th edn. Lippincott William & Wilkins, Philadelphia, p 1261–1289

  33. Targher G, Montagnana M, Salvagno G, Moghetti P, Zoppini G, Muggeo M, Lippi G (2008) Association between serum TSH, free T4, and serum liver enzyme activities in a large cohort of unselected outpatients. Clin Endocrinol 68:481–484

    Article  CAS  Google Scholar 

  34. Targher G, Day CP, Bonora E (2010) Risk of cardiovascular disease in patients with nonalcoholic fatty liver disease. N Engl J Med 363:1341–1350

    Article  PubMed  CAS  Google Scholar 

  35. Tominaga K, Kurata JH, Chen YK, Fujimoto E, Miyagawa S, Abe I, Kusano Y (1995) Prevalence of fatty liver in Japanese children and relationship to obesity: an epidemiological ultrasonographic survey. Dig Dis Sci 40:2002–2009

    Article  PubMed  CAS  Google Scholar 

  36. Valentina VN, Marijan B, Chedo D, Branka K (2011) Subclinical hypothyroidism and risk to carotid atherosclerosis. Arq Bras Endocrinol Metabol 55:475–480

    Article  PubMed  Google Scholar 

  37. Vanderpump MP, Tunbridge WM, French JM, Appleton D, Bates D, Clark F, Grimley EJ, Rodgers H, Tunbridge F, Young ET (1996) The development of ischemic heart disease in relation to autoimmune thyroid disease in a 20-year follow-up study of an English community. Thyroid 6:155–160

    PubMed  CAS  Google Scholar 

  38. Willeit J, Kiechl S, Oberhollenrer F, Rungger G, Egger G, Bonora E, Mitterer M, Muggeo M (2000) Distinct risk profiles of early and advanced atherosclerosis. Arterioscler Tromb Vasc Biol 20:529–537

    Article  CAS  Google Scholar 

  39. Yazici M, Gorgulu S, Sertbas Y, Erbilen E, Albayrak S, Yildiz O, Uyan C (2004) Effects of thyroxin therapy on cardiac function in patients with subclinical hypothyroidism: index of myocardial performance in the evaluation of left ventricular function. Int J Cardiol 95:135–143

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Pediatric Cardiology, Konya Training and Research Hospital, 42080, Konya, Turkey

    Ahmet Sert, Ebru Aypar & Dursun Odabas

  2. Department of Pediatric Endocrinology and Diabetes, Faculty of Medicine, S. Demirel University, Isparta, Turkey

    Ozgur Pirgon

  3. Department of Radiology, Konya Training and Research Hospital, Konya, Turkey

    Hakan Yilmaz

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  1. Ahmet Sert
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  2. Ozgur Pirgon
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Correspondence to Ahmet Sert.

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Sert, A., Pirgon, O., Aypar, E. et al. Subclinical Hypothyroidism as a Risk Factor for the Development of Cardiovascular Disease in Obese Adolescents With Nonalcoholic Fatty Liver Disease. Pediatr Cardiol 34, 1166–1174 (2013). https://doi.org/10.1007/s00246-013-0638-z

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