CLINICAL STUDY Cardiovascular risk, metabolic profile, and body composition in adult males with congenital adrenal hyperplasia due to 21-hydroxylase deficiency Henrik Falhammar 1,2 , Helena Filipsson Nystro ¨m 3 , Anna Wedell 2 and Marja Thore ´n 1,2 1 Department of Endocrinology, Metabolism and Diabetes, and 2 Department of Molecular Medicine and Surgery, Karolinska University Hospital and Karolinska Institutet, SE-171 76 Stockholm, Sweden and 3 Department of Endocrinology, Sahlgrenska University Hospital and Sahlgrenska Academy, University of Gothenburg, Go ¨teborg, Sweden (Correspondence should be addressed to H Falhammar at Department of Endocrinology, Metabolism and Diabetes, Karolinska University Hospital and Karolinska Institutet; Email: henrik.falhammar@ki.se) Abstract Objective: Lifelong glucocorticoid therapy in patients with congenital adrenal hyperplasia (CAH) or the disease per se may result in increased cardiovascular risk. We therefore investigated cardiovascular and metabolic risk profiles in adult CAH males. Subjects and methods: We compared CAH males (nZ30), 19–67 years old, with age- and sex-matched controls (nZ32). Subgroups of different ages (!30 years or older) and CYP21A2 genotypes (null, I2splice, and I172N as the mildest mutation) were studied. Anthropometry, fat and lean mass measured by dual-energy X-ray absorptiometry, lipids, liver function tests, homocysteine, lipoprotein- (a), glucose and insulin during an oral glucose tolerance test (OGTT), urine albumin, adrenal hormones, and 24 h ambulatory blood pressure measurements were studied. Results: CAH males were shorter. Waist/hip ratio and fat mass were higher in older patients and the I172N group. Heart rate was faster in older patients, the I2splice, and I172N groups. Insulin levels were increased during OGTT in all patients and in the I172N group. g-glutamyl transpeptidase was increased in older patients and in the I172N group. Testosterone was lower in older patients. Homocysteine was lower in younger patients, which may be cardioprotective. The cardiovascular risk seemed higher with hydrocortisone/cortisone acetate than prednisolone. Urinary epinephrine was lower in all groups of patients except in I172N. Conclusions: Indications of increased risk were found in CAH males R30 years old and in the I172N group. In contrast, younger CAH males did not differ from age-matched controls. This is likely to reflect a better management in recent years. European Journal of Endocrinology 164 285–293 Introduction Congenital adrenal hyperplasia (CAH) causes adrenal androgen excess and varying extent of cortisol and aldosterone deficiency. More than 95% of cases are due to 21-hydroxylase deficiency and three phenotypes are recognized (1). There are two classic forms, the salt- wasting form (SW) manifested neonatally by severe salt loss, and the simple virilizing form (SV) where salt loss is mild or absent. The nonclassic (NC) variant is usually diagnosed with hyperandrogenism later in childhood or adulthood with most males being identified in the course of family investigations (1). There is generally a good phenotype-to-genotype correlation (2), and genotypes may predict outcomes better than phenotypes (3–7). The consequences of having CAH throughout adult life are incompletely investigated and there are circumstances with the potential to bring about increased cardiovascular morbidity and mortality. Glucocorticoids, the foundation of CAH treatment, is often given in supraphysiological doses to normalize the adrenal androgens, which may lead to unfavorable metabolic consequences: obesity, insulin resistance with type 2 diabetes (T2DM), and hypertension. Long- standing undertreatment with elevation of adrenal androgens may also reduce insulin sensitivity (8, 9) and induce hypogonadism with low testosterone values by gonadotropin suppression. Hypogonadotropic hypo- gonadism has been shown to be a risk factor for the metabolic syndrome and T2DM and to increase cardiovascular mortality (10). Inadequate mineralocor- ticoid therapy for aldosterone deficiency may also have negative impact on the vascular system (11). Previous reports on cardiovascular and metabolic profiles in CAH adults have mainly included young females, in spite of the fact that males in general have a higher European Journal of Endocrinology (2011) 164 285–293 ISSN 0804-4643 q 2011 European Society of Endocrinology DOI: 10.1530/EJE-10-0877 Online version via www.eje-online.org Downloaded from Bioscientifica.com at 04/23/2021 09:45:39AM via free access