Unfavourable trends in cardiovascular and metabolic risk in paediatric and adult patients with congenital adrenal hyperplasia?

Aim: Adverse outcomes in adult congenital adrenal hyperplasia (CAH) patients are frequent. The determinants of them have not yet been established. Objective: To establish the prevalence of adverse outcomes and to find determining factors for each of them. Design, patients, and methods: Cross-sectional monocentric study of 104 patients with childhood onset of CAH (71 women, 33 men). Analysis established first the determinants of clinical, hormonal, genetic variables and second a composite criterion for some of the outcomes and determinants. Results: BMI was above 25 kg/m 2 in 44% of the cohort, adrenal hyperplasia and/or nodules were present in 45% of the patients, and irregular menstrual cycles and hyperandrogenism were found in 50 and 35% of the women respectively. In univariate analysis, the determinants of these outcomes were all linked to disease control, especially 17-hydroxyprogesterone (17OHP) and androstenedione concentrations. Low weight was a determinant of abnormal bone mineral density (BMD) (60% of the cohort). Multivariate analysis confirmed these data. A classic form (CF) of CAH was a determinant of testicular adrenal rest tumors (TARTs) (36% of the men). Total cumulative glucocorticoid dose was a determinant of BMI and TART, whereas fludrocortisone dose was a determinant of TART (PZ0.03). In men, the composite criterion was associated with androstenedione concentration and CF. In women, the composite criterion was associated with total testosterone concentration. Conclusion:The present study confirms the high prevalence of adverse outcomes in CAH patients. These are, most often, related to disease control. The impaired health status of adults with CAH could therefore be improved through the modification of treatment.

Section: Discussionmentioning

confidence: 52%

Determining clinical and biological indicators for health outcomes in adult patients with childhood onset of congenital adrenal hyperplasia

Bachelot¹,

Golmard²,

Jérôme³

et al. 2015

“…Hypogonadotropic hypogonadism has been shown to be a risk factor for the metabolic syndrome and T2DM and to increase cardiovascular mortality (10). Inadequate mineralocorticoid 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 cardiovascular risk, and the results have been contradictory (6,8,9,(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22).…”

Section: Introductionmentioning

confidence: 92%

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

Falhammar¹,

Nyström²,

Wedell³

et al. 2011

105

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.

“…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).…”

Section: Discussionmentioning

confidence: 99%

“…A recently published review suggests that adult CAH patients have a cluster of metabolic risk factors, consistent with the metabolic syndrome (14). However, many of the studies on adults with 21OHD included small patient samples and represent single specialist centres, which could imply selection bias.…”

Section: Introductionmentioning

confidence: 99%

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

Nermoen

Brønstad

Fougner

et al. 2012

Objective: The aim of this study was to determine the genetic, anthropometric and metabolic features in an unselected population of adult Norwegian patients with 21-hydroxylase deficiency (21OHD). Patients, methods and design: Sixty-four 21OHD patients participated (23 men and 41 women; median age 38.5 years; range 19-72 years) in a cross-sectional study including DNA sequencing of CYP21A2, anthropometric measurements including dual X-ray absorptiometry scanning and biochemical analyses. The results were compared with reference cohorts from the general population. Results: We identified four novel and plausibly disease-causing CYP21A2 mutations. Gene deletions/conversions (42.1% of alleles), the splice mutation I2 splice (23.0%) and point mutation I172 N (22.2%) were common. The genotype corresponded to clinical phenotype in 92% of the patients. The prevalence of osteopenia was 48% in males and 34% in females. Both men and women had normal BMI but markedly increased fat mass compared with the normal population. Diastolic blood pressure was higher than normal. Thirty-nine per cent of the women had testosterone levels above the normal range; 13% of the men had testosterone levels below normal. Reduced final height was more pronounced in men (median K11.2 cm, K1.77 SDS) than in women (K6.3 cm, K1.07 SDS). Conclusions: In this population-based survey of 21OHD, we identified four novel mutations and high concordance between genotype and phenotype. The patients had increased fat mass, increased diastolic blood pressure, reduced final height and high frequency of osteopenia among males. These results show unfavourable metabolic features in 21OHD patients indicating a need for improvement of treatment and follow-up.