Health status of adults with congenital adrenal hyperplasia: a cohort study of 203 patients

Wiebke Arlt, Debbie S Willis, Sarah H Wild, Nils Krone, Emma J Doherty, Stefanie Hahner, Thang S Han, Paul V Carroll, Gerry S Conway, D Aled Rees, Roland H Stimson, Brian R Walker, John M C Connell, Richard J Ross, United Kingdom Congenital Adrenal Hyperplasia Adult Study Executive (CaHASE), W Arlt, U Ayyagari, S Ball, J S Bevan, S A Booth, U Bradley, L Breen, P V Carroll, M Clements, T Chambers, T R Cole, J M C Connell, G Conway, M Daly, J R Davis, A Doane, E J Doherty, T S Han, I A Hughes, S Hunter, V Ibbotson, N Krone, J MacDonald, K Mullen, S Peacey, C Perry, D W Ray, D A Rees, R J M Ross, M Scanlon, H Simpson, P M Stewart, S E Stewart, R H Stimson, J P Vora, D Wake, E Walker, B R Walker, J A H Wass, P Whittingham, D S Willis, D Wright, F C Wu, Wiebke Arlt, Debbie S Willis, Sarah H Wild, Nils Krone, Emma J Doherty, Stefanie Hahner, Thang S Han, Paul V Carroll, Gerry S Conway, D Aled Rees, Roland H Stimson, Brian R Walker, John M C Connell, Richard J Ross, United Kingdom Congenital Adrenal Hyperplasia Adult Study Executive (CaHASE), W Arlt, U Ayyagari, S Ball, J S Bevan, S A Booth, U Bradley, L Breen, P V Carroll, M Clements, T Chambers, T R Cole, J M C Connell, G Conway, M Daly, J R Davis, A Doane, E J Doherty, T S Han, I A Hughes, S Hunter, V Ibbotson, N Krone, J MacDonald, K Mullen, S Peacey, C Perry, D W Ray, D A Rees, R J M Ross, M Scanlon, H Simpson, P M Stewart, S E Stewart, R H Stimson, J P Vora, D Wake, E Walker, B R Walker, J A H Wass, P Whittingham, D S Willis, D Wright, F C Wu

Abstract

Context: No consensus exists for management of adults with congenital adrenal hyperplasia (CAH) due to a paucity of data from cohorts of meaningful size.

Objective: Our objective was to establish the health status of adults with CAH.

Design and setting: We conducted a prospective cross-sectional study of adults with CAH attending specialized endocrine centers across the United Kingdom.

Patients: Participants included 203 CAH patients (199 with 21-hydroxylase deficiency): 138 women, 65 men, median age 34 (range 18-69) years.

Main outcome measures: Anthropometric, metabolic, and subjective health status was evaluated. Anthropometric measurements were compared with Health Survey for England data, and psychometric data were compared with appropriate reference cohorts.

Results: Glucocorticoid treatment consisted of hydrocortisone (26%), prednisolone (43%), dexamethasone (19%), or a combination (10%), with reverse circadian administration in 41% of patients. Control of androgens was highly variable with a normal serum androstenedione found in only 36% of patients, whereas 38% had suppressed levels suggesting glucocorticoid overtreatment. In comparison with Health Survey for England participants, CAH patients were significantly shorter and had a higher body mass index, and women with classic CAH had increased diastolic blood pressure. Metabolic abnormalities were common, including obesity (41%), hypercholesterolemia (46%), insulin resistance (29%), osteopenia (40%), and osteoporosis (7%). Subjective health status was significantly impaired and fertility compromised.

Conclusions: Currently, a minority of adult United Kingdom CAH patients appear to be under endocrine specialist care. In the patients studied, glucocorticoid replacement was generally nonphysiological, and androgen levels were poorly controlled. This was associated with an adverse metabolic profile and impaired fertility and quality of life. Improvements in the clinical management of adults with CAH are required.

Trial registration: ClinicalTrials.gov NCT00749593.

Figures

Figure 1
Figure 1
Expected and recruited number of CAH patients in the United Kingdom. Age distribution of recruited male (A) and female (B) CAH patients from 17 endocrine specialist centers across the United Kingdom (C) in comparison with the expected number of classic CAH patients based on United Kingdom population data (Office of National Statistics) and an assumed incidence of one in 12,000 newborns. A and B show absolute numbers (white bars, normal population; black bars, CAH patients); D shows percentage of the expected patient number per age group (gray bars, males; black bars, females).
Figure 2
Figure 2
Serum levels of the androgen precursor androstenedione (A, C) and the glucocorticoid precursor 17OHP (B, D) in male and female CAH patients sampled in the morning after intake of the usual glucocorticoid morning dose. The shaded areas represent recommended target range (2). Note the logarithmic scale used for representing the serum hormone concentrations.
Figure 3
Figure 3
Subjective health in status in CAH according to SF-36 (A) and HADS (B) questionnaires and shown for male classic (n = 65), female classic (n = 103), and female nonclassic (n = 31) CAH patients with box plots representing median and interquartile ranges; whiskers represent the 5th and 95th percentiles. A z-score of 0 represents the median of the normal reference population; the lower the SF-36 z-scores and the higher the HADS z-scores, the worse is self-perceived wellbeing and mood. SF-36 dimensions: PF, physical functioning; RP, role limitations due to physical problems; BP, bodily pain; GH, general health; VT, vitality; SF, social functioning; RE, role limitations due to emotional problems; MH, mental health.

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Source: PubMed

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