Advanced Biomedical Research

Cardiovascular risk factors in children and adolescents with congenital adrenal hyperplasia

Document Type : Original Article

Authors

1 Child Growth and Development Research Center, Research Institute for Primordial Prevention of Non-Communicable Disease, Isfahan University of Medical Sciences, Isfahan, Iran

2 Department of Pediatrics Endocrinology, Faculty of Medical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran

3 Endocrine and Metabolism Research Center, Isfahan University of Medical Sciences, Isfahan, Iran

Abstract

Background: Congenital adrenal hyperplasia (CAH) is an autosomal recessive disorder caused by impaired steroidogenesis. Glucocorticoid treatment with increased androgens may lead to cardiovascular and metabolic effects in these patients. In this study, we investigated the relationship between cardiovascular risk factors and androgen levels in children and adolescents with CAH due to 21 hydroxylase deficiency. Materials and Methods: A cross-sectional study of 78 patients (37 boys and 41 girls) with CAH aged 3–17 years. Anthropometric, body mass index (BMI), systolic (SBP), and diastolic (DBP) blood pressure were measured. Fasting blood glucose with plasma insulin and lipids were measured, and insulin resistance (HOMA-IR) calculated using the homeostasis assessment model. Furthermore, testosterone, Dehydroepiandrosterone sulfate (DHEAS), and 17-Hydroxyprogesterone (17OHP) were investigated. Results: The mean SBP and DBP were 112.01 ± 19.13 and 69.77 ± 7.56, respectively. The mean of HOMA-IR in patients was 2.25 ± 1.46. The frequency of patients with overweight and High HOMA index were, respectively, 33.3% and 29.3%. The correlation analysis between clinical characteristics and androgen serum levels showed that DBP and BMI had a significant positive correlation with 17OHP. The median regression analysis showed, only DBP in the adjusted model had a significant positive effect with 17OHP level (P < 0.05), and no significant relationship was observed for other characteristics. Conclusion: A significant association was found between BMI and DBP with serum concentrations of 17-OHP, suggesting that elevated 17-OHP can lead to an increased risk of cardiovascular disorders in children and adolescents with CAH.

Keywords

1.
Charmandari E, Chrousos GP. Metabolic syndrome manifestations in classic congenital adrenal hyperplasia: Do they predispose to atherosclerotic cardiovascular disease and secondary polycystic ovary syndrome? Ann N Y Acad Sci 2006;1083:37-53.  Back to cited text no. 1
    
2.
Yau M, Nimkarn S, New MI. Congenital adrenal hyperplasia. In: Genetic Diagnosis of Endocrine Disorders. Academic Press Elsevier; 2016. p. 203-10.  Back to cited text no. 2
    
3.
White PC, Speiser PW. Congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Endocr Rev 2000;21:245-91.  Back to cited text no. 3
    
4.
El-Maouche D, Arlt W, Merke DP. Congenital adrenal hyperplasia. Lancet 2017;390:2194-210.  Back to cited text no. 4
    
5.
Pande Dwipayana IM, Sudjana K, Semadi S, Suastika K, Ratna Saraswati M, Gotera W. Simple virilization type of classic congenital adrenal hyperplasia: Case report. Biomed Pharmacol J 2018;11:1345-50.  Back to cited text no. 5
    
6.
Mendes-Dos-Santos CT, De Lemos-Marini SH, Baptista MT, Guerra G, De-Mello MP, Paulino MF, et al. Normalization of height and excess body fat in children with salt-wasting 21-hydroxylase deficiency. J Pediatr (Rio J) 2011;87:263-8.  Back to cited text no. 6
    
7.
Rabbani B, Mahdieh N, Haghi Ashtiani MT, Akbari MT, Rabbani A. Molecular diagnosis of congenital adrenal hyperplasia in Iran: Focusing on CYP21A2 gene. Iran J Pediatr 2011;21:139-50.  Back to cited text no. 7
    
8.
Kim MS, Dao-Tran A, Davidowitz E, Tseng T, Gilsanz V, Ryabets-Lienhard A, 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;85:242-9.  Back to cited text no. 8
    
9.
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.  Back to cited text no. 9
    
10.
Falhammar H, Frisén L, Hirschberg AL, Norrby C, Almqvist C, Nordenskjöld A, 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;100:3520-8.  Back to cited text no. 10
    
11.
Falhammar H, Filipsson H, Holmdahl G, Janson PO, Nordenskjöld A, Hagenfeldt K, et al. Metabolic profile and body composition in adult women with congenital adrenal hyperplasia due to 21-hydroxylase deficiency. J Clin Endocrinol Metab 2007;92:110-6.  Back to cited text no. 11
    
12.
Falhammar H, Filipsson Nyström H, Wedell A, Thorén M. Cardiovascular risk, metabolic profile, and body composition in adult males with congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Eur J Endocrinol 2011;164:285-93.  Back to cited text no. 12
    
13.
Zimmermann A, Grigorescu-Sido P, AlKhzouz C, Patberg K, Bucerzan S, Schulze E, et al. Alterations in lipid and carbohydrate metabolism in patients with classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Horm Res Paediatr 2010;74:41-9.  Back to cited text no. 13
    
14.
Speiser PW, Azziz R, Baskin LS, Ghizzoni L, Hensle TW, Merke DP, et al. Congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency: An endocrine society clinical practice guideline. J Clin Endocrinol Metab 2010;95:4133-60.  Back to cited text no. 14
    
15.
Walker IV, Smith CR, Davies JH, Inskip HM, Baird J. Methods for determining pubertal status in research studies: literature review and opinions of experts and adolescents. J Dev Orig Health Dis. 2020; 11, 168-187.  Back to cited text no. 15
    
16.
Frese EM, Fick A, Sadowsky HS. Blood pressure measurement guidelines for physical therapists. Cardiopulm Phys Ther J 2011;22:5-12.  Back to cited text no. 16
    
17.
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;28:412-9.  Back to cited text no. 17
    
18.
Beyazal Polat H, Çeliker M, Özyurt S, Terzi S, Özgür A. Insulin resistance and affecting factors in patients with obstructive sleep apnea syndrome. Int J Otorhinolaryngol Head Neck Surg 2017;3:986.  Back to cited text no. 18
    
19.
Manzoor Mughal A, Hassan N, Ahmed A. Bone age assessment methods: A critical review. Pak J Med Sci 2014;30:211-5.  Back to cited text no. 19
    
20.
Mtaweh H, Tuira L, Floh AA, Parshuram CS. Indirect calorimetry: History, technology, and application. Front Pediatr 2018;6:257.  Back to cited text no. 20
    
21.
Jéquier E, Felber JP. Indirect calorimetry. Baillieres Clin Endocrinol Metab 1987;1:911-35.  Back to cited text no. 21
    
22.
Kokubo Y, Iwashima Y. Higher Blood Pressure as a Risk Factor for Diseases Other Than Stroke and Ischemic Heart Disease. Hypertension 2015;66:254-9.  Back to cited text no. 22
    
23.
Mooij CF, Kroese JM, Claahsen-van der Grinten HL, Tack CJ, Hermus AR. Unfavourable trends in cardiovascular and metabolic risk in paediatric and adult patients with congenital adrenal hyperplasia? Clin Endocrinol (Oxf) 2010;73:137-46.  Back to cited text no. 23
    
24.
Tamhane S, Rodriguez-Gutierrez R, Iqbal AM, Prokop LJ, Bancos I, Speiser PW, et al. Cardiovascular and metabolic outcomes in congenital adrenal hyperplasia: A systematic review and meta-analysis. J Clin Endocrinol Metab 2018;103:4097-103.  Back to cited text no. 24
    
25.
Finkielstain GP, Kim MS, Sinaii N, Nishitani M, Van Ryzin C, Hill SC, et al. Clinical characteristics of a cohort of 244 patients with congenital adrenal hyperplasia. J Clin Endocrinol Metab 2012;97:4429-38.  Back to cited text no. 25
    
26.
Roche EF, Charmandari E, Dattani MT, Hindmarsh PC. Blood pressure in children and adolescents with congenital adrenal hyperplasia (21-hydroxylase deficiency): A preliminary report. Clin Endocrinol (Oxf) 2003;58:589-96.  Back to cited text no. 26
    
27.
Bonfig W, Roehl FW, Riedl S, Dörr HG, Bettendorf M, Brämswig J, et al. Blood pressure in a large cohort of children and adolescents with classic adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency. Am J Hypertens 2016;29:266-72.  Back to cited text no. 27
    
28.
Mooij CF, van Herwaarden AE, Sweep FC, Roeleveld N, de Korte CL, Kapusta L, et al. Cardiovascular and metabolic risk in pediatric patients with congenital adrenal hyperplasia due to 21 hydroxylase deficiency. J Pediatr Endocrinol Metab 2017;30:957-66.  Back to cited text no. 28
    
29.
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 (Oxf) 2014;80:471-7.  Back to cited text no. 29
    
30.
Nebesio TD, Eugster EA. Observation of hypertension in children with 21-hydroxylase deficiency: A preliminary report. Endocrine 2006;30:279-82.  Back to cited text no. 30
    
31.
Völkl TM, Simm D, Dötsch J, Rascher W, Dörr HG. Altered 24-hour blood pressure profiles in children and adolescents with classical congenital adrenal hyperplasia due to 21-hydroxylase deficiency. J Clin Endocrinol Metab 2006;91:4888-95.  Back to cited text no. 31
    
32.
Hoepffner W, Herrmann A, Willgerodt H, Keller E. Blood pressure in patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency. J Pediatr Endocrinol Metab 2006;19:705-11.  Back to cited text no. 32
    
33.
Völkl TM, Simm D, Beier C, Dörr HG. Obesity among children and adolescents with classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Pediatrics 2006;117:e98-105.  Back to cited text no. 33
    
34.
Paredes S, Alves M, Carvalho F, Gomes MM, Martins S, Marques O, et al. Cardiovascular and metabolic risk factors in children and adolescents with congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Endocr Abstr 2019; 63, 880  Back to cited text no. 34
    
35.
Diouf A, Adom T, Aouidet A, El Hamdouchi A, Joonas NI, Loechl CU, et al. Body mass index vs deuterium dilution method for establishing childhood obesity prevalence, Ghana, Kenya, Mauritius, Morocco, Namibia, Senegal, Tunisia and United Republic of Tanzania. Bull World Health Organ 2018;96:772-81.  Back to cited text no. 35
    
36.
Pasquali R. Obesity and androgens: Facts and perspectives. Fertil Steril 2006;85:1319-40.  Back to cited text no. 36
    
37.
Zhao Y, Hou L, Jie GH, Zhan D, Zhang C, Ping LX. Independent relationship between body mass index and LH peak value of GnRH stimulation test in ICPP girls: A cross-sectional study. J Huazhong Univ Sci Technolog Med Sci 2017;37:556-62.  Back to cited text no. 37
    
38.
Tony Nengom J, Sap Ngo Um S, Chelo D, Mbono Betoko R, Boombhi J, Mouafo Tambo F, et al. Assessment of cardiac function in children with congenital adrenal hyperplasia: A case control study in Cameroon. BMC Pediatr 2017;17:109.  Back to cited text no. 38
Advanced Biomedical Research
Volume 2021, july
July 2021
Pages 1-6