Endocrine Abstracts

Background: Classic congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is characterized by impaired cortisol synthesis, requiring life-long glucocorticoid (GC) replacement therapy. Given the detrimental systemic effects of GCs in the long term, the aim of our study was to assess whether CAH patients have increased metabolic and cardiovascular alterations compared with age-matched controls.

Materials and methods: For this cross-sectional study 29 patients with CAH were submitted to biochemical and hormonal testing, oral glucose tolerance test (OGTT), intima-media thickness (IMT) evaluation and compared to 21 controls matched for age, sex, BMI and smoking-habits. The effects of different GC regimens (dexamethasone, DEX vs dual-release hydrocortisone, DR-HC) on metabolic parameters and quality of life were also assessed.

Results: IMT was higher in CAH than in controls at right and left common carotids (0.8 ± 0.3 vs 0.68 ± 0.12 mm, P < 0.001 and 0.8 ± 0.35 vs 0.68 ± 0.17 mm, P < 0.001) and carotid bulbs (0.8 ± 0.2 vs 0.64 ± 0.18 mm, P < 0.0001 and 1 ± 0.35 vs 0.62 ± 0.13 mm, P < 0.0001). Patients on DEX treatment had taken lower cumulative GC dose during the last 3 years compared to those on DR-HC and daily dose normalized for body surface area (7.18 ± 4.18 and 10.77 ± 2.76 mg/m², P = 0.045). Despite lower equivalent doses, patients taking DEX showed better disease control with lower 17-hydroxyprogesterone (respectively, 40.5 ± 230.76 vs 741 ± 893.5 nmol/l, P = 0.008) and ACTH (respectively, 32 ± 58 vs 652.5 ± 855.25 ng/l, P = 0.016). However, DEX therapy was associated with higher glucose levels during OGTT with an overall more elevated AUC__glucose (32.9 ± 9.58 vs 21.45 ± 6.77, P = 0.005) than DR-HC without differences in insulin curves. To add, DEX induced an increase in clotting factors II (143.95 ± 35.55% vs 109.55 ± 25.5%, P = 0.039) and X (106 ± 6.24% vs 96.5 ± 8.2%, P = 0.05), followed by a compensatory increase in antithrombin (106 ± 6.24% vs 96.5 ± 8.2%, P < 0.005), protein C (113.8 ± 23.99% vs 92.35 ± 27%, P = 0.006) and plasminogen (108.9 ± 17.04% vs 89.5 ± 28.03%, P = 0.025) compared to DR-HC.

Conclusions: Patients with CAH have a higher cardiovascular risk which is probably due to both chronic GC treatment and the disease itself. The negative effects of GCs on glucose metabolism and coagulative cascade depend not only on the total GC dose, but also on the type of drug taken and probably on its time of administration. DEX proved to be effective in suppressing adrenal androgen secretion to the detriment of a less favourable glucose profile. Conversely, DR-HC, even administered at higher equivalent dose, did not guarantee a comparable disease control, but showed a lower metabolic impact. Our results pinpointed the need to individualize GC therapy in CAH on the basis of each patient’s characteristics.