Background: Classic 21-hydroxylase deficiency (21HD) presents some traits of the metabolic syndrome. Aim: To characterize discrete alterations of lipid and carbohydrate metabolism in children and young adults with classic 21HD, which could predict early atherogenesis. Patients and Methods: Twenty-seven Caucasian patients with classic 21HD (4–31 years); 27 sex-, age- and BMI-matched controls. Clinical parameters, hormonal status and genotype were assessed in all patients. Lipid parameters, including relative (%) and absolute (mg/dl) small-dense low-density lipoproteins subfractions (sd-LDL) were measured in patients and controls. Oral glucose tolerance tests were performed in both groups. Results: sd-LDL (%) was significantly higher in patients than controls (39.7 ± 5.9 vs. 35.5 ± 5.7%; p = 0.008). The same applies for absolute sd-LDL (mg/dl) (42.6 ± 11.9 vs. 36.4 ± 7.5; p = 0.029). HDL-cholesterol was lower in patients (p = 0.032). Fasting glucose and insulin were significantly higher in patients. Similar differences were noticed for HOMA-IR (p = 0.001), IRI (p = 0.001) and HOMA-B (p = 0.002). IRI correlated directly and significantly with the total hydrocortisone dose and the duration of treatment. Fasting glucose correlated with absolute sd-LDL. No obvious differences were seen between clinical forms or genotype groups. Conclusions: Substitution therapy should be adapted particularly at young ages to prevent early atherogenesis and cardiovascular risk in later life.

1.
Speiser PW, White PC: Congenital adrenal hyperplasia. N Engl J Med 2003;349:776–788.
2.
New MI, Ghizzoni L: Congenital adrenal hyperplasia; in Lifschitz F (ed): Pediatric Endocrinology, ed 4. New York, Marcel Dekker, 2003, pp 175–178.
3.
Merke DP, Bornstein SR: Congenital adrenal hyperplasia. Lancet 2005;365:2125–2136.
4.
Völkl TM, Simm S, Beier C, Dorr HG: Obesity among children and adolescents with classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Pediatrics 2006;117:e98–e105.
5.
Stikkelbroeck NM, Oyen WJG, Van der Wilt GJ, Hermus MM, 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.
6.
Charmandari E, Weise M, Bornstein S, Eisenhofer G, Keil MF, Chrousis GP, Merke DP: Children with classic congenital hyperplasia have elevated serum leptin concentrations and insulin resistance: potential clinical implications. J Clin Endocrinol Metab 2002;87:2114–2120.
7.
Riepe FG, Krone N, Krüger SN, Sweep FC, Lenders JW, Dötsch J, Mönig H, Sippel WG, Partsch CJ: Absence of exercise-induced leptin suppression associated with insufficient epinephrine reserve in patients with classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Exp Clin Endocrinol Diabetes 2006;114:105–110.
8.
Roche E, 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;58:589–596.
9.
Falhammar H, Filipsson H, Holmdahl G, Janson PO, Nordenskjold A, Hagenfeldt K, Thoren M: Metabolic profile and body composition in adult women with congenital adrenal hyperplasia due to 21-hydroxylase deficiency. J Clin Endocrinol Metab 2007;92:110–116.
10.
Paula FJ, Gouveia GM, Piccinato CE, Moreira AC, Foss MC: Androgen – related effects on peripheral glucose metabolism in women with congenital adrenal hyperplasia. Horm Metab Res 1994;26:552–556.
11.
Bachelot A, Plu-Bureau G, Thibaud E, Laborde K, Pinto G, Samara D, Nihoul-Fékété C, Kuttenn F, Polak M, Touraine P: Long-term outcome of patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Horm Res 2007;67:268–276.
12.
Fleischman A, Paltiel H, Chow J, Ringelheim J, Gordon CM: Normal ovarian structure and function with normal glucose tolerance in girls with early treatment of classic congenital adrenal hyperplasia. J Pediatr Adolesc Gynecol 2007;20:67–72.
13.
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 NY Acad Sci 2006;1083:37–53.
14.
Chapman MJ, Goldstein S, Lagrange D, Laplaud PM: A density gradient ultracentrifugal procedure for the isolation of the major lipoprotein classes from human serum. J Lipid Res 1981;22:339–358.
15.
Nigon F, Lesnik P, Rouis M, Chapman MJ: Discrete subspecies of human low density lipoproteins are heterogenous in their interaction with the cellular LDL receptor. J Lipid Res1991;32:1741–1753.
16.
Austin MA, Breslow CH, Hennekens CH, Buring JE, Willet WC, Krauss RM: Low-density lipoprotein subclass patterns and risk of myocardial infarction. J Am Med Assoc 1988;260:1917–1921.
17.
Lamarche B, Tchernof A, Moorjani S, Chantin B, Dagenais GR, Lupien PJ, Despres JP: Small, dense low-density lipoprotein particles as a predictor of the risk of ischemic heart disease in men. Circulation 1997;95:69–75.
18.
Vakkilainen J, Steiner G, Ansquer JC, Aaubin F, Rattier S, Foucher C, Hamsten A, Taskinen MR: Relationships between LDL lipoprotein particle size, plasma lipoproteins and progression of coronary artery disease. Circulation 2003;107:1733–1737.
19.
Krone N, Braun A, Roscher AA, Knorr D, Schwartz HP: Predicting phenotype in steroid 21-hydroxylase deficiency? Comprehensive genotyping in 155 unrelated, well-defined patients from Southern Germany. J Clin Endocrinol Metab 2000;85:1059–1065.
20.
Grigorescu-Sido A, Weber MM, Grigorescu-Sido P, Clausmeyer S, Heinrich U, Schulze E: 21-Hydroxylase and 11β-hydroxylase mutations in Romanian patients with classic congenital adrenal hyperplasia. J Clin Endocrinol Metab 2005;90:5769–5773.
21.
Miller WL: The adrenal cortex; in Rudolph AM, Hofmann JIE (eds): Pediatrics. Norwalk, Appleton & Lange, 1991, pp 1584–1613.
22.
Reincken L, van Oost G: Longitudinale Körperentwicklung gesunder Kinder von 0–18 Jahren. Körperlänge, -höhe, Körpergewicht und Wachstumsgeschwindigkeit. Klin Pädiatr 1992;204:129–133.
23.
Greulich WW, Pyle SI: Radiographic Atlas of Skeletal Development of the Hand and Wrist, ed 2. Stanford, Stanford University Press, 1959.
24.
Geiss HC, Bremer S, Barrett PHR, Otto C, Parhofer KG: In vivo metabolism of LDL subfractions in patients with homozygous FH on statin therapy: rebound analysis of LDL subfractions after LDL apheresis. J Lipid Res 2004;45:1459–1467.
25.
Genuth S, Alberti KG, Bennett P, et al: Follow-up report on the diagnosis of diabetes mellitus. Diabetes Care 2003;26:3160.
26.
Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC: Homeostasis model assessment: insulin resistance and β-cells function from fasting plasma glucose and insulin concentration in men. Diabetologia 1985;28:412–419.
27.
Monzillo LU, Osama H: Evaluation of insulin sensitivity in clinical practice and in research settings. Nutr Rev 2003;61:397–412.
28.
Sartorato P, Zulian E, Benedini S, Mariniello B, Schiavi F, Bilora F, Pozzan G, Greggio N, Pagnan A, Mantero F, Scaroni C: Cardiovascular risk factors and ultrasound evaluation of intima-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.
29.
Wajchenberg BL: Subcutaneous and visceral adipose tissue: their relation to the metabolic syndrome. Endocr Rev 2000;21:697–738.
30.
Fernandez-Real JM, Ricart W: Insulin resistance and chronic cardiovascular inflammatory syndrome. Endocr Rev 2003;24:278–301.
31.
Daniels SR: Cardiovascular disease risk factors and atherosclerosis in children and adolescents. Curr Atheroscler Rep 2001;3:479–485.
32.
Lyon CJ, Law RE, Hsueh WA: Minireview: adiposity, inflammation and atherogenesis. Endocrinology 2003;144:2195–2200.
33.
Calles-Escandon J, Cipolla M: Diabetes and endothelial dysfunction: a clinical perspective. Endocr Rev 2001;22:36–52.
34.
Livingstone C, Collison M: Sex steroids and insulin resistance. Clin Sci 2002;102:151–166.
35.
Vitarius JA: The metabolic syndrome and cardiovascular disease. Mt Sinai J Med 2005;72:257–262.
36.
Quyyumi AA: Endothelial function in health and disease: new insights into the genesis of cardiovascular disease. Am J Med 1998;105:32S–39S.
37.
Dunaif A: Insulin resistance and the polycystic ovary syndrome: mechanism and implications for pathogenesis. Endcr Rev 1997;18:774–800.
38.
Cole TJ, Freeman JV, Preece MA: Body mass index reference curves for the UK, 1990. Arch Dis Childh 1995;73:25–29.
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