Cardiovascular risk, metabolic profile, and body composition in adult males with congenital adrenal hyperplasia due to 21-hydroxylase deficiency

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.

Genetic, anthropometric and metabolic features of adult Norwegian patients with 21-hydroxylase deficiency

“…Although we did not find higher BMI than the reference population, we found markedly increased body fat mass in both men and women. The high fat mass in younger women is at variance with data from Sweden showing fat mass in female and male 21OHD patients similar to age-matched controls but increased fat mass in male patients older than 30 years (32,33). One explanation could be the higher hydrocortisone equivalent dose used by the young Norwegian females (38.9 mg/day) compared with the young Swedish females (33.3 mg/day).…”

“…The glucocorticoid doses were also higher than the hydrocortisone doses of 15-25 mg/day suggested by the Endocrine Society (3). We previously reported that only 47% of the Norwegian patients use mineralocorticoid (17), which compared with 84% of the Swedish patients (32,33), which could contribute to the differences in both glucocorticoid doses and body composition. High blood pressure, including isolated diastolic hypertension, is, like fat mass, a marker of risk of cardiovascular disease (34).…”

“…In paediatric and adolescent patients, blood pressure has showed a tendency towards elevation in some (35) but not in all studies (14). Some small studies have addressed blood pressure in adult patients, showing no difference in single blood pressure or 24-h blood pressure measurements compared with controls (32,33). However, Arlt et al (30) recently found increased diastolic blood pressure in 102 female 21OHD patients compared with national data in the UK.…”

Bone mineral density, bone markers, and fractures in adult males with congenital adrenal hyperplasia

“…Male controls, one for each patient and born on the same date as each patient, were recruited from the National Population Registry. Characteristics of this cohort have been reported earlier (25,26).…”

“…Testosterone, estradiol and dried blood spot 17OHP (measured at 0800, 1400, 1900, 0100, and 0600 h), and 24-h urinary pregnanetriol were measured as described previously (25,26 …”