ESPE Abstracts

Background: Hypoglycaemia and poor cardiovascular outcomes are described in children and young people (CYP) with primary adrenal insufficiency (PAI). In this study, we described cortisol exposure during hydrocortisone replacement therapy, glucose regulation by continuous glucose monitoring (CGM) and cardiovascular function. Here, we present the final study data.

Methods: CYP with PAI underwent CGM for 7 days using Dexcom G6. Vascular health was assessed from measurements of carotid intima media thickness (CIMT) and flow mediated dilatation (FMD). Office blood pressure (BP) and where possible, ambulatory blood pressure monitoring (ABPM) were performed. HOMA-IR was determined from fasting insulin and glucose concentrations. Data were analysed by the independent t-test and Mann Whitney U tests.

Results: 26 (15M) CYP with PAI (Addison’s disease n=4, congenital adrenal hyperplasia (CAH) n =21, and PAI of unknown aetiology n =1;) aged 9.4±5.1 years were recruited. Hydrocortisone doses were 11.0±4.4mg/m2/day, height SDS -0.04±1.21 and BMI SDS 0.89±1.36. Mean glucose levels were higher in the PAI group than in reference data from a healthy paediatric population (6.01±0.55mmol/l vs 5.47mmol/L±0.36, P<0.001).1 Coefficient variability did not differ between PAI and reference data (P=0.409), however, the percentage of time >8.8mmol/l and 7.7mmol/l was significantly higher (P<0.001). In 7/25 (28%) CYP systolic BP was >95th centile, and diastolic BP >95th centile in 4/25 (16%). ABPM was tolerated in only nine participants: 1/9 had a systolic BP >90th centile and 3/9 showed loss of nocturnal dipping of BP, a known risk factor of cardiovascular disease. CIMT measurements were obtained in 20 participants and was ≥95th centile in 5 (25%). FMD was measured in 18 participants and was low in 6 (33%). HOMA-IR was raised in 4/14 (28.6%) in whom it was measured.

Conclusion: Cardiovascular studies, such as ABPM and vascular ultrasound scanning can be poorly tolerated in CYP leading to challenges in obtaining full datasets. Poor cardiovascular outcomes have been reported in adults with childhood onset PAI. Our data suggest that cardiovascular morbidity may have its onset in childhood, through disrupted glucose metabolism, vascular dysfunction, raised blood pressure and insulin resistance. If these findings are confirmed in larger studies, it might be that early intervention in childhood, to modify these risk factors, may improve long term outcomes. 1 Shah, V.N., et al., Continuous Glucose Monitoring Profiles in Healthy Nondiabetic Participants: A Multicenter Prospective Study. J Clin Endocrinol Metab, 2019. 104(10): p. 4356-4364.