title: The impact of adrenal insufficiency and its treatment on regulation of glucose, cardiovascular health, and growth parameters.
Creators: name: Park, Julie
Publisher: name: University of Liverpool Repository
Year: 2024

description: Introduction: Cortisol affects glycaemic control, raising concerns for children with both primary (PAI) and secondary (SAI). Cardiovascular events are rare in childhood, however increased cardiovascular morbidity and mortality are described in adults. Obesity, hypertension, increased carotid intima media thickness (CIMT), decreased flow mediated dilation (FMD) and insulin resistance are independent risk factors for cardiovascular disease. Salivary hormone sampling may be useful to guide diagnosis and treatment. Materials and methods: Two studies, one assessing children with PAI and the second assessing children with SAI, investigated glucose concentrations via continuous glucose monitoring (CGM) for seven days using Dexcom G6®. Data were compared with healthy children. Study participants also underwent assessment of clinic blood pressure (BP), ambulatory blood pressure monitoring (ABPM), measurement of CIMT and FMD, fasting blood glucose, homeostatic model assessment of insulin resistance (HOMA-IR) and lipid profiling to assess cardiovascular risk. Salivary cortisol and cortisone and other adrenal biomarker concentrations were measured throughout the day. Results: 26 children with PAI and 20 children with SAI took part. Mean glucose concentrations were significantly higher in AI groups compared to healthy children (PAI: 6.1±0.6mmol/L); SAI:5.9±0.40mmol/L; controls 5.5±0.36mmol/L, p&lt;0.001 in both cohorts). Glucose variability was not different. One child with PAI had hypoglycaemia (&lt;3mmol/L for 2% of the time) which improved with an increase in hydrocortisone dose (9.2mg/m2/day to 9.8mg/m2/day). Both cohorts showed evidence of increased body mass index (BMI) and HOMA-IR, particularly the SAI group. Hypertension was prevalent in younger children with PAI on higher doses of fludrocortisone, and in SAI. Increased CIMT and reduced FMD were seen across both groups. Salivary cortisol was high in both groups, likely due to contamination with hydrocortisone. Both groups showed salivary cortisone had similar total cortisone exposure compared to healthy children. However, when pre and post dosing salivary samples were taken in the SAI group peaks and troughs were seen. Testosterone and A4 were higher in children with Addison’s disease compared to the healthy population. 11KT and 11OHA4 were lower in Addison’s disease. Testosterone, A4, 11KT and 11OHA4 were higher in children with congenital adrenal hyperplasia (CAH) compared to healthy children. Discussion: Novel findings shows higher mean glucose concentrations in children with AI compared to healthy children, of which has an unclear significance. Cardiovascular risk factors are evident in childhood. Interventions to ensure a healthy lifestyle, weight management, diet and exercise are important to address regularly with children with AI. Interventions are needed to reduce cardiovascular morbidity and mortality in this cohort. Salivary hormone markers including cortisol, cortisone, testosterone, A4, 11KT and 11OHA4 may be useful for monitoring disease and treatment. 11KT and 11OHA4 needs further research to assess their underlying effect and what concentrations suggest good control of disease. Conclusion: These two observational studies show higher mean glucose concentrations measured by CGM and increased cardiovascular risk factors in children with AI. Salivary hormones are different to those found in healthy children and may be useful markers for monitoring treatment of CAH.