Hostname: page-component-745bb68f8f-mzp66 Total loading time: 0 Render date: 2025-01-10T21:37:59.719Z Has data issue: false hasContentIssue false
  • English
  • Français

Periaortic fat thickness and cardiovascular risk factors in children with congenital adrenal hyperplasia

Published online by Cambridge University Press:  10 January 2025

Nesibe Akyürek Open the ORCID record for Nesibe Akyürek [Opens in a new window] ,
Beray Selver Eklioğlu ,
Mehmet Emre Atabek ,
Hayrullah Alp Open the ORCID record for Hayrullah Alp [Opens in a new window]  and
Halil Ibrahim Gün
Nesibe Akyürek*
Affiliation:
Department of Pediatric Endocrinology, Başkent University Faculty of Medicine, Konya Training and Research Hospital, Konya, Turkey
Beray Selver Eklioğlu
Affiliation:
Department of Pediatric Endocrinology, Necmettin Erbakan University Faculty of Medicine, Konya, Turkey
Mehmet Emre Atabek
Affiliation:
Department of Pediatric Endocrinology, Necmettin Erbakan University Faculty of Medicine, Konya, Turkey
Hayrullah Alp
Affiliation:
Department of Pediatric Cardiology, Karamanoğlu Mehmetbey Üniversity Faculty of Medicine, Karaman, Turkey
Halil Ibrahim Gün
Affiliation:
Department of Pediatric Endocrinology, Necmettin Erbakan University Faculty of Medicine, Konya, Turkey
*
Corresponding author: Nesibe Akyürek; Email: n_akyurek@yahoo.com.tr
Get access Rights & Permissions [Opens in a new window]

Abstract

Objective:

Children with congenital adrenal hyperplasia are considered to be at an elevated risk for cardiovascular morbidity and mortality. The objective of this study was to evaluate the association between periaortic fat thickness and the cardiometabolic profile in children diagnosed with congenital adrenal hyperplasia.

Method:

A total of 20 children and adolescents with congenital adrenal hyperplasia and 20 healthy control subjects were enrolled in the study. We investigated metabolic and anthropometric parameters, comparing these values to those of the control group. Periaortic fat thickness was assessed using an echocardiographic method that has not previously been applied to paediatric patients with congenital adrenal hyperplasia.

Results:

The subjects in the congenital adrenal hyperplasia group were significantly shorter than the control subjects (p = 0.021) and exhibited a higher body mass index (p = 0.044) and diastolic blood pressure (p = 0.046). No significant differences were observed between the congenital adrenal hyperplasia group and control subjects concerning age, weight, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol levels. Additionally, dyslipidemia was identified in 5% (N = 1) of the congenital adrenal hyperplasia group. The mean fasting glucose, fasting insulin, homeostasis model assessment of insulin resistance, and fasting glucose-to-fasting insulin ratio were similar between the congenital adrenal hyperplasia group and the control subjects. However, 15% (n = 3) of the congenital adrenal hyperplasia group had insulin resistance. Two children with congenital adrenal hyperplasia (10%) were diagnosed with hypertension.

Periaortic fat thickness was significantly greater in the congenital adrenal hyperplasia group compared to the control group (p = 0.000), with measurements of 0.2039 ± 0.045 mm in the congenital adrenal hyperplasia group and 0.1304 ± 0.022 mm in the control group. In children with congenital adrenal hyperplasia, periaortic fat thickness exhibited a negative correlation with high-density lipoprotein cholesterol (r = −0.549, p = 0.034) and a positive correlation with the dose of hydrocortisone (r = 0.688, p = 0.001).

Conclusion:

Our results provide further evidence of subclinical cardiovascular disease in children with congenital adrenal hyperplasia. It is crucial to regularly assess cardiometabolic risk in children with congenital adrenal hyperplasia. The measurement of periaortic fat thickness in this population may serve as a valuable tool for identifying individuals at high risk for developing early atherosclerosis.

Keywords

cardiovascular diseasecongenital adrenal hyperplasiaperiaortic fat thickness
Type
Original Article
Information
Cardiology in the Young , First View , pp. 1 - 5
Check for updates
Copyright
© The Author(s), 2025. Published by Cambridge University Press

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Espinosa Reyes, TM, Pesántez Velepucha, AK, Cabrera Rego, JO, Valdés Gómez, W, Domínguez Alonso, E, Falhammar, H. Cardiovascular risk in Cuban adolescents and young adults with congenital adrenal hyperplasia. BMC Endocr Disord 2023; 23: 241.CrossRefGoogle Scholar
Kim, MS, Dao-Tran, A, Davidowitz, E et al. Carotid intima-media thickness is associated with increased androgens in adolescents and young adults with classical congenital adrenal hyperplasia. Horm Res Paediatr 2016; 85: 242–249.CrossRefGoogle Scholar
Improda, N, Barbieri, F, Ciccarelli, GP, Capalbo, D, Salerno, M. Cardiovascular health in children and adolescents with congenital adrenal hyperplasia due to 21-hydroxilase deficiency. Front Endocrinol (Lausanne) 2019; 10: 212.CrossRefGoogle ScholarPubMed
Falhammar, H, Frisén, L, Hirschberg, AL et al. Increased cardiovascular and metabolic morbidity in patients with 21-hydroxylase deficiency: a Swedish population-based national cohort study. J Clin Endocrinol Metab 2015; 100: 3520–3528.CrossRefGoogle ScholarPubMed
Subbarayan, A, Dattani, MT, Peters, CJ, Hindmarsh, PC. Cardiovascular risk factors in children and adolescents with congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Clin Endocrinol 2014; 80: 471–477.CrossRefGoogle ScholarPubMed
Falhammar, H, Filipsson Nystrom, H, Wedell, A, Thoren, M. Cardiovascular risk, metabolic profile, and body composition in adult males with congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Eur J Endocrinol 2011; 164: 285–293.CrossRefGoogle ScholarPubMed
Metwalley, KA, Farghaly, HS, Abdelhamid, A. Epicardial fat thickness in children with classic congenital adrenal hyperplasia. J Clin Res Pediatr Endocrinol 2019; 11: 61–69.CrossRefGoogle ScholarPubMed
Barreto, TM, Botelho, C, Soares, JL, Andrade, EM, Matos, AV, Novato, I. Cardiovascular risk factors and increased carotid intima-media thickness in young patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Arch Endocrinol Metab 2015; 59: 541–547.Google Scholar
Pacifico, L, Nobili, V, Anania, C, Verdecchia, P, Chiesa, C. Pediatric nonalcoholic fatty liver disease, metabolic syndrome and cardiovascular risk. World J Gastroenterol 2011; 17 : 3082–3091.Google ScholarPubMed
Joint LWPES/ESPE CAH Working Group. Consensus statement on 21-hydroxylase deficiency from the lawson wilkins pediatric endocrine society and the European society for paediatric endocrinology. J Clin Endocrinol Metab 2002; 87: 4048–4053.CrossRefGoogle Scholar
Kuczmarski, RJ, Ogden, CL, Guo, SS et al. CDC growth charts for the United States: methods and development. Vital Health Stat 11 2000; 246: 1–190.Google Scholar
Zimmet, P, Alberti, G, Kaufman, F et al. International diabetes federation task force on epidemiology and prevention of diabetes. The metabolicsyndrome in children and adolescents. Lancet 2007; 369: 2059–2061.CrossRefGoogle Scholar
Matthews, DR, Hosker, JP, Rudenski, AS, Naylor, BA, Treacher, DF, Turner, RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985; 28: 412–419.CrossRefGoogle ScholarPubMed
Keskin, M, Kurtoglu, S, Kendirci, M, Atabek, ME, Yazici, C. 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 2005; 115: 500–503.CrossRefGoogle Scholar
National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents. The fourth report on the diagnosis, evaluation, and treatmentof high blood pressure in children and adolescents. Pediatrics 2004; 114: 555–576.CrossRefGoogle Scholar
Hashemi Dehkordi, E, Khaheshi, S, Mostofizadeh, N, Hashemipour, M. Cardiovascular risk factors in children and adolescents with congenital adrenal hyperplasia. Adv Biomed Res 2021; 10: 19.CrossRefGoogle ScholarPubMed
Yang, L, Magnussen, CG, Yang, L, Bovet, P, Xi, B. Elevated blood pressure in childhood or adolescence and cardiovascular outcomes in adulthood: a systematic review. Hypertension 2020; 75: 948–955.CrossRefGoogle ScholarPubMed
Hansen, ML, Gunn, PW, Kaelber, DC. Underdiagnosis of hypertension in children and adolescents. JAMA 2007; 298: 874–879.CrossRefGoogle ScholarPubMed
Sorof, JM, Lai, D, Turner, J, Poffenbarger, T, Portman, RJ. Overweight, ethnicity, and the prevalence of hypertension in school-aged children. Pediatrics 2004; 113: 475–482.CrossRefGoogle ScholarPubMed
Maccabee-Ryaboy, N, Thomas, W, Kyllo, J et al. Hypertension in children with congenital adrenal hyperplasia. Clin Endocrinol 2016; 85: 528–534.CrossRefGoogle ScholarPubMed
Akyürek, N, Atabek, ME, Eklioğlu, BS. Alp H.Ambulatory blood pressure and subclinical cardiovascular disease in patients with congenital adrenal hyperplasia: a preliminary report. J Clin Res Pediatr Endocrinol 2015; 7: 13–18.CrossRefGoogle ScholarPubMed
Roche, EF, Charmandari, E, Dattani, MT, Hindmarsh, PC. Blood pressure in children and adolescents with congenital adrenalhyperplasia (21-hydroxylase deficiency): a preliminary report. Clin Endocrinol 2003; 58: 589–596.CrossRefGoogle Scholar
Finkielstain, GP, Kim, MS, Sinaii, N et al. Clinical characteristics of a cohort of 244 patients with congenital adrenal hyperplasia. J Clin Endocrinol Metab 2012; 97: 4429–4438.CrossRefGoogle ScholarPubMed
Mooij, CF, Kroese, JM, Sweep, FCGJ, Hermus, ARMM, Tack, CJ. Adult patients with congenital adrenal hyperplasia have elevated blood pressure but otherwise a normal cardiovascular risk profile. PLoS One 2011; 6: e24204.CrossRefGoogle ScholarPubMed
Ubertini, G, Bizzarri, C, Grossi, A et al. Blood pressure and left ventricular characteristics in young patients with classical congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Int J Pediatr Endocrinol 2009; 2009: 383610–383616.CrossRefGoogle Scholar
de Silva, KSH, Kanumakala, S, Brown, JJ, Jones, CL, Warne, GL. 24-hour ambulatory blood pressure profile in patients with congenital adrenal hyperplasia: a preliminary report. J Pediatr Endocrinol Metab 2004; 17: 1089–1095.CrossRefGoogle ScholarPubMed
Sartorato, P, Zulian, E, Benedini, S et al. Cardiovascular risk factors and ultrasound evaluation ofintima-media thickness at common carotids,carotid bulbs, and femoral and abdominal aorta arteries in patients with classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency. J Clin Endocrinol Metab 2007; 92: 1015–1018.CrossRefGoogle ScholarPubMed
Januś, D, Wójcik, M, Tyrawa, K et al. Circadian blood pressure profiles and ambulatory arterial stiffness index in children and adolescents with congenital adrenal hyperplasia due to 21-hydroxylase deficiency in relation to their genotypes. Neuroendocrinol Lett 2017; 38: 509–518.Google ScholarPubMed
Merke, DP, Chrousos, GP, Eisenhofer, G et al. Adrenomedullary dysplasia and hypofunction in patients with classic 21-hydroxylase deficiency. N Engl J Med 2000; 343: 1362–1368.CrossRefGoogle ScholarPubMed
Balagamage, C, Lawrence, NR, Krone, R, Bacila, IA, Krone, NP. Blood pressure in children with congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Horm Res Paediatr 2024; 97(4):315–325. DOI: 10.1159/000533465.CrossRefGoogle ScholarPubMed
Charmandari, E, Weise, M, Bornstein, SR et al. Children with classic congenital adrenal hyperplasia have elevated serum leptin concentrations and insulin resistance: potential clinical implications. J Clin Endocrinol Metab 2002; 87: 2114–2120. DOI: 10.1210/jcem.87.5.8456.CrossRefGoogle ScholarPubMed
Arlt, W, Willis, DS, Wild, SH et al. Health status of adults with congenital adrenal hyperplasia: a cohort study of 203 patients. J Clin Endocrinol Metab 2010; 95 : 5110–5121.CrossRefGoogle ScholarPubMed
Amr, NH, Ahmed, AY, Ibrahim, YA. Carotid intima media thickness and other cardiovascular risk factors in children with congenital adrenal hyperplasia. J Endocrinol Invest 2014; 37: 1001–1008. DOI: 10.1007/s40618-014-0148-8.CrossRefGoogle ScholarPubMed
Zimmermann, A, Grigorescu-Sido, P, AlKhzouz, C et al. Alterations in lipid and carbohydrate metabolism in patients with classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Horm Res Paediatr 2010; 74: 41–49. DOI: 10.1159/000313368.CrossRefGoogle ScholarPubMed
Marra, AM, Improda, N, Capalbo, D et al. Cardiovascular abnormalities and impaired exercise performance in adolescents with congenital adrenal hyperplasia. J Clin Endocrinol Metab 2015; 100: 644–652. DOI: 10.1210/jc.2014-1805.CrossRefGoogle ScholarPubMed
Kim, MS, Ryabets-Lienhard, A, Dao-Tran, A. Increased abdominal adiposity in adolescents and young adults with classical congenital adrenal hyperplasia due to 21- hydroxylase deficiency. J Clin Endocrinol Metab 2015; 100: E1153–E1159. DOI: 10.1210/jc.2014-4033.CrossRefGoogle Scholar
Tamhane, S, Rodriguez-Gutierrez, R, Iqbal, AM et al. Cardiovascular and metabolic outcomes in congenital adrenal hyperplasia: a systematic review and meta-analysis. J Clin Endocrinol Metab 2018; 103: 4097–4103.CrossRefGoogle ScholarPubMed
Gonçalves, EM, de Lemos-Marini, SH, de Mello, MP et al. Impairment in anthropometric parameters and body composition in females with classical 21-hydroxylase deficiency. J Pediatr Endocrinol Metab 2009; 22: 519–529.CrossRefGoogle ScholarPubMed
Stikkelbroeck, NMML, Oyen, WJG, van der Wilt, G-J, Hermus, ARMM, Otten, BJ. Normal bone mineral density and lean body mass, but increased fat mass, in young adult patients with congenital adrenal hyperplasia. J Clin Endocrinol Metab 2003; 88: 1036–1042.CrossRefGoogle Scholar
Speiser, PW, Arlt, W, Auchus, RJ et al. Congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 2018; 103:4043–4088. DOI: 10.1210/jc.2018-01865.CrossRefGoogle ScholarPubMed
Watts, SW, Burnett, R, Dorrance, AM, Shaw, S. Indoleamine 2,3-diooxygenase in periaortic fat: mechanisms of inhibition of contraction. Am J Physiol Heart Circ Physiol 2011; 301: H1236–H1247.CrossRefGoogle ScholarPubMed
Yudkin, JS, Eringa, E, Stehouwer, CDA. “Vasocrine” signalling from perivascular fat: a mechanism linking insulin resistance to vascular disease. Lancet 2005; 365:1817–1820.CrossRefGoogle Scholar
Greenstein, AS, Khavandi, K, Withers, SB et al. Local inflammation and hypoxia abolish the protective anticontractile properties of perivascular fat in obese patients. Circulation 2009; 119: 1661–1670.CrossRefGoogle ScholarPubMed
Antonopoulos, AS, Antoniades, C, Bakogiannis, C et al. Adiponectin as a link between type 2 diabetes and vascular NADPH oxidase activity in the human arterial wall: the regulatory role of perivascular adipose tissue. Diabetes 2015; 64: 2207–2219.CrossRefGoogle ScholarPubMed
Antonopoulos, AS, Sanna, F, Sabharwal, N et al. Detecting human coronary inflammation by imaging perivascular fat. Sci Transl Med 2017; 9: eaal2658.CrossRefGoogle ScholarPubMed
Yun, CH, Bezerra, HG, Wu, TH et al. The normal limits, subclinical significance, related metabolic derangements and distinct biological effects of body site-specific adiposity in relatively healthy population. PLoS One 2013; 8: e61997.CrossRefGoogle ScholarPubMed