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Semin Reprod Med 2009; 27(4): 316-321
DOI: 10.1055/s-0029-1225259
© Thieme Medical Publishers

Cardiovascular Disease Risk in Adult Women with Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency

Mimi S. Kim1 , Deborah P. Merke1
  • 1Reproductive Biology and Medicine Branch, The Eunice Kennedy Shriver National Institute of Child Health and Human Development, and The National Institutes of Health Clinical Center, Bethesda, Maryland
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Publication History

Publication Date:
15 June 2009 (online)

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ABSTRACT

Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is a common autosomal recessive disorder characterized by impaired cortisol biosynthesis, with or without aldosterone deficiency, and androgen excess. Patients with the classic (severe) form also have epinephrine deficiency. Patients with CAH have an increased prevalence of risk factors for cardiovascular disease including obesity, hypertension, and insulin resistance. Androgen excess in women appears to be an additional risk factor for cardiovascular disease. Carotid intima-media thickness, a measure of subclinical atherosclerosis, also has been found to be increased in adults with CAH. The multiple hormonal imbalances present in the adult woman with CAH, in combination with chronic glucocorticoid therapy, contribute to cardiovascular disease risk. Further investigation of the predisposition to cardiovascular disease in women with CAH is warranted. Longitudinal studies are needed, and interventions targeting obesity, insulin resistance, hypertension, and hyperandrogenism may offer improved outcome.

KEYWORDS

Cardiovascular risk - congenital adrenal hyperplasia - metabolic syndrome - hyperandrogenism

REFERENCES

  • 1 Merke D P, Bornstein S R. Congenital adrenal hyperplasia.  Lancet. 2005;  365 2125-2136
    CrossrefPubMedGoogle Scholar
  • 2 Orio F, Palomba S, Colao A. Cardiovascular risk in women with polycystic ovary syndrome.  Fertil Steril. 2006;  86(Suppl 1) S20-S21
    PubMedGoogle Scholar
  • 3 Orio Jr F, Palomba S, Spinelli L et al.. The cardiovascular risk of young women with polycystic ovary syndrome: an observational, analytical, prospective case-control study.  J Clin Endocrinol Metab. 2004;  89 3696-3701
    CrossrefPubMedGoogle Scholar
  • 4 National Institutes of Health .Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). NIH Publication 01–3670. Bethesda, MD; National Institutes of Health 2001
    Google Scholar
  • 5 Kristo C, Ueland T, Godang K, Aukrust P, Bollerslev J. Biochemical markers for cardiovascular risk following treatment in endogenous Cushing's syndrome.  J Endocrinol Invest. 2008;  31 400-405
    PubMedGoogle Scholar
  • 6 Arnaldi G, Mancini T, Polenta B, Boscaro M. Cardiovascular risk in Cushing's syndrome.  Pituitary. 2004;  7 253-256
    CrossrefPubMedGoogle Scholar
  • 7 Merke D P. Approach to the adult with congenital adrenal hyperplasia due to 21-hydroxylase deficiency.  J Clin Endocrinol Metab. 2008;  93 653-660
    CrossrefPubMedGoogle Scholar
  • 8 Debono M, Ghobadi C, Rostami-Hodjegan A et al.. Modified-release hydrocortisone to provide circadian cortisol profiles.  J Clin Endocrinol Metab. 2009;  94 1548-1554
    CrossrefPubMedGoogle Scholar
  • 9 Chen M J, Yang W S, Yang J H, Chen C L, Ho H N, Yang Y S. Relationship between androgen levels and blood pressure in young women with polycystic ovary syndrome.  Hypertension. 2007;  49 1442-1447
    CrossrefPubMedGoogle Scholar
  • 10 Mantzoros C S, Georgiadis E I, Young R et al.. Relative androgenicity, blood pressure levels, and cardiovascular risk factors in young healthy women.  Am J Hypertens. 1995;  8 606-614
    CrossrefPubMedGoogle Scholar
  • 11 Wild R A, Applebaum-Bowden D, Demers L M et al.. Lipoprotein lipids in women with androgen excess: independent associations with increased insulin and androgen.  Clin Chem. 1990;  36 283-289
    PubMedGoogle Scholar
  • 12 Dokras A. Cardiovascular disease risk factors in polycystic ovary syndrome.  Semin Reprod Med. 2008;  26 39-44
    Article in Thieme ConnectPubMedGoogle Scholar
  • 13 Huppert J, Chiodi M, Hillard P J. Clinical and metabolic findings in adolescent females with hyperandrogenism.  J Pediatr Adolesc Gynecol. 2004;  17 103-108
    CrossrefPubMedGoogle Scholar
  • 14 Golden S H, Ding J, Szklo M, Schmidt M I, Duncan B B, Dobs A. Glucose and insulin components of the metabolic syndrome are associated with hyperandrogenism in postmenopausal women: the atherosclerosis risk in communities study.  Am J Epidemiol. 2004;  160 540-548
    CrossrefPubMedGoogle Scholar
  • 15 Moghetti P, Tosi F, Castello R et al.. The insulin resistance in women with hyperandrogenism is partially reversed by antiandrogen treatment: evidence that androgens impair insulin action in women.  J Clin Endocrinol Metab. 1996;  81 952-960
    CrossrefPubMedGoogle Scholar
  • 16 Nestler J E. Metformin for the treatment of the polycystic ovary syndrome.  N Engl J Med. 2008;  358 47-54
    CrossrefPubMedGoogle Scholar
  • 17 Charmandari E, Weise M, Bornstein S R 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
    CrossrefPubMedGoogle Scholar
  • 18 Sartorato P, Zulian E, Benedini S et al.. 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
    PubMedGoogle Scholar
  • 19 Falhammar H, Filipsson H, Holmdahl G et al.. Metabolic profile and body composition in adult women with congenital adrenal hyperplasia due to 21-hydroxylase deficiency.  J Clin Endocrinol Metab. 2007;  92 110-116
    PubMedGoogle Scholar
  • 20 Speiser P W, Serrat J, New M I, Gertner J M. Insulin insensitivity in adrenal hyperplasia due to nonclassical steroid 21-hydroxylase deficiency.  J Clin Endocrinol Metab. 1992;  75 1421-1424
    CrossrefPubMedGoogle Scholar
  • 21 Saygili F, Oge A, Yilmaz C. Hyperinsulinemia and insulin insensitivity in women with nonclassical congenital adrenal hyperplasia due to 21-hydroxylase deficiency: the relationship between serum leptin levels and chronic hyperinsulinemia.  Horm Res. 2005;  63 270-274
    CrossrefPubMedGoogle Scholar
  • 22 Bachelot A, Plu-Bureau G, Thibaud E et al.. Long-term outcome of patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency.  Horm Res. 2007;  67 268-276
    CrossrefPubMedGoogle Scholar
  • 23 Nonogaki K. New insights into sympathetic regulation of glucose and fat metabolism.  Diabetologia. 2000;  43 533-549
    CrossrefPubMedGoogle Scholar
  • 24 Riepe F G, Krone N, Krüger S N et al.. 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
    Article in Thieme ConnectPubMedGoogle Scholar
  • 25 Weise M, Mehlinger S L, Drinkard B et al.. Patients with classic congenital adrenal hyperplasia have decreased epinephrine reserve and defective glucose elevation in response to high-intensity exercise.  J Clin Endocrinol Metab. 2004;  89 591-597
    CrossrefPubMedGoogle Scholar
  • 26 Niswender K D, Magnuson M A. Obesity and the beta cell: lessons from leptin.  J Clin Invest. 2007;  117 2753-2756
    CrossrefPubMedGoogle Scholar
  • 27 Martikainen H, Salmela P, Nuojua-Huttunen S et al.. Adrenal steroidogenesis is related to insulin in hyperandrogenic women.  Fertil Steril. 1996;  66 564-570
    PubMedGoogle Scholar
  • 28 New M I. Polycystic ovarian disease and congenital and late-onset adrenal hyperplasia.  Endocrinol Metab Clin North Am. 1988;  17 637-648
    PubMedGoogle Scholar
  • 29 Hague W M, Adams J, Rodda C et al.. The prevalence of polycystic ovaries in patients with congenital adrenal hyperplasia and their close relatives.  Clin Endocrinol (Oxf). 1990;  33 501-510
    CrossrefPubMedGoogle Scholar
  • 30 Ogden C L, Flegal K M, Carroll M D, Johnson C L. Prevalence and trends in overweight among US children and adolescents, 1999-2000.  JAMA. 2002;  288 1728-1732
    CrossrefPubMedGoogle Scholar
  • 31 Flegal K M, Carroll M D, Ogden C L, Johnson C L. Prevalence and trends in obesity among US adults, 1999-2000.  JAMA. 2002;  288 1723-1727
    CrossrefPubMedGoogle Scholar
  • 32 Ford E S, Giles W H, Dietz W H. Prevalence of the metabolic syndrome among US adults: findings from the third National Health and Nutrition Examination Survey.  JAMA. 2002;  287 356-359
    CrossrefPubMedGoogle Scholar
  • 33 National Institutes of Health . Clinical guidelines on the identification, evaluation, and treatment of overweight and obesity in adults–the evidence report.  Obes Res. 1998;  6(Suppl 2) 51S-209S
    PubMedGoogle Scholar
  • 34 Burke V, Beilin L J, Simmer K et al.. Predictors of body mass index and associations with cardiovascular risk factors in Australian children: a prospective cohort study.  Int J Obes (Lond). 2005;  29 15-23
    CrossrefPubMedGoogle Scholar
  • 35 Weiss R, Dufour S, Taksali S E et al.. Prediabetes in obese youth: a syndrome of impaired glucose tolerance, severe insulin resistance, and altered myocellular and abdominal fat partitioning.  Lancet. 2003;  362 951-957
    CrossrefPubMedGoogle Scholar
  • 36 Wajchenberg B L, Giannella-Neto D, da Silva M E, Santos R F. Depot-specific hormonal characteristics of subcutaneous and visceral adipose tissue and their relation to the metabolic syndrome.  Horm Metab Res. 2002;  34 616-621
    Article in Thieme ConnectPubMedGoogle Scholar
  • 37 Stikkelbroeck N M, Oyen W J, van der Wilt G J, Hermus A R, Otten B J. 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
    CrossrefPubMedGoogle Scholar
  • 38 Christiansen P, Mølgaard C, Müller J. Normal bone mineral content in young adults with congenital adrenal hyperplasia due to 21-hydroxylase deficiency.  Horm Res. 2004;  61 133-136
    CrossrefPubMedGoogle Scholar
  • 39 Hagenfeldt K, Martin Ritzén E, Ringertz H, Helleday J, Carlström K. Bone mass and body composition of adult women with congenital virilizing 21-hydroxylase deficiency after glucocorticoid treatment since infancy.  Eur J Endocrinol. 2000;  143 667-671
    CrossrefPubMedGoogle Scholar
  • 40 Cornean R E, Hindmarsh P C, Brook C G. Obesity in 21-hydroxylase deficient patients.  Arch Dis Child. 1998;  78 261-263
    PubMedGoogle Scholar
  • 41 Völkl T M, Simm D, Beier C, Dörr H G. Obesity among children and adolescents with classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency.  Pediatrics. 2006;  117 e98-e105
    CrossrefPubMedGoogle Scholar
  • 42 Isguven P, Arslanoglu I, Mesutoglu N, Yildiz M, Erguven M. Bioelectrical impedance analysis of body fatness in childhood congenital adrenal hyperplasia and its metabolic correlates.  Eur J Pediatr. 2008;  167 1263-1268
    CrossrefPubMedGoogle Scholar
  • 43 Pasquali R, Vicennati V, Gambineri A, Pagotto U. Sex-dependent role of glucocorticoids and androgens in the pathophysiology of human obesity.  Int J Obes (Lond). 2008;  32 1764-1779
    CrossrefPubMedGoogle Scholar
  • 44 Roche E F, Charmandari E, Dattani M T, Hindmarsh P C. Blood pressure in children and adolescents with congenital adrenal hyperplasia (21-hydroxylase deficiency): a preliminary report.  Clin Endocrinol (Oxf). 2003;  58 589-596
    CrossrefPubMedGoogle Scholar
  • 45 Völkl T M, Simm D, Dötsch J, Rascher W, Dörr H G. 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 4888-4895
    CrossrefPubMedGoogle Scholar
  • 46 Nebesio T D, Eugster E A. Observation of hypertension in children with 21-hydroxylase deficiency: a preliminary report.  Endocrine. 2006;  30 279-282
    CrossrefPubMedGoogle Scholar
  • 47 Botero D, Arango A, Danon M, Lifshitz F. Lipid profile in congenital adrenal hyperplasia.  Metabolism. 2000;  49 790-793
    CrossrefPubMedGoogle Scholar
  • 48 Bloomgarden Z T. Inflammation and insulin resistance.  Diabetes Care. 2003;  26 1922-1926
    CrossrefPubMedGoogle Scholar
  • 49 Hajer G R, van Haeften T W, Visseren F L. Adipose tissue dysfunction in obesity, diabetes, and vascular diseases.  Eur Heart J. 2008;  29 2959-2971
    CrossrefPubMedGoogle Scholar
  • 50 Witchel S F, DeFranco D B. Mechanisms of disease: regulation of glucocorticoid and receptor levels—impact on the metabolic syndrome.  Nat Clin Pract Endocrinol Metab. 2006;  2 621-631
    CrossrefPubMedGoogle Scholar

Deborah P MerkeM.D. M.S. 

National Institutes of Health Clinical Center

10 Center Drive, Building 10, Room 1-2740, MSC 1932, Bethesda, MD 20892-1932

Email: dmerke@nih.gov