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Glucose pattern in children with classical congenital adrenal hyperplasia: evidence from continuous glucose
Alfonso Galderisi1,2, Dulanjalee Kariyawasam1,3,4,5, Athanasia Stoupa1,3,4,5
1Department of Paediatric Endocrinology, Diabetology, and Gynaecology, Necker-Enfants Malades University Hospital, Centre de Référence des Maladies endocriniennes Rares de la Croissance et du Développement (filière FIRENDO), AP-HP Centre, Paris, France.
Insights
Children with congenital adrenal hyperplasia (CAH) show disrupted daily glucose patterns, with increased hypoglycemia risk during nighttime and morning hours. Lower cortisol levels correlate with more frequent hypoglycemic events in CAH patients.
Area of Science:
- Pediatric Endocrinology
- Metabolic Disorders
- Genetics
Background:
- Classical congenital adrenal hyperplasia (CAH) poses risks for hypoglycemia, particularly during acute illness.
- Limited data exists on asymptomatic hypoglycemia and daily glucose patterns in children with CAH.
Purpose of the Study:
- To investigate the daytime glucose profile in children diagnosed with classical CAH.
- To explore the relationship between glucose patterns, cortisol, and adrenocorticotropic hormone (ACTH) levels.
Main Methods:
- An observational study involving 11 children with classical CAH on hydrocortisone and fludrocortisone therapy.
- Utilized 14-day continuous glucose monitoring (CGM) sessions and 24-hour serial cortisol/ACTH measurements.
- Analyzed glucose data across three daytime periods relative to hydrocortisone dosing and cortisol nadir.
Main Results:
- CGM revealed a disrupted daily glucose pattern in children with CAH.
- Higher percentages of time with glucose <70 mg/dL occurred during 10 PM-7 AM and 7 AM-4 PM compared to 4 PM-10 PM.
- Nighttime hypoglycemia (<65 mg/dL) was observed for 10.9% of the time, correlating with lower 7 AM and 10 PM cortisol levels.
Conclusions:
- Continuous glucose monitoring highlights a disturbed diurnal glucose rhythm in pediatric CAH.
- Lower cortisol concentrations are associated with increased hypoglycemia risk in children with CAH.
Background:
While the risk for hypoglycemia during acute illness is well described in children with classical congenital adrenal hyperplasia (CAH), there is little evidence for the prevalence of asymptomatic hypoglycemia and the daily glucose patterns in CAH. Herein, we explored the daytime glucose profile of children with classical CAH.
Methods:
We conducted an observational study in 11 children (6 female; age 3.1 years [1.4, 5.1]; body mass index 17.3 kg/m2 [15.6, 17.9]) with a genetic diagnosis of classical CAH receiving hydrocortisone and fludrocortisone replacement therapy. Participants underwent 2 14-day continuous glucose monitoring (CGM) sessions and an inpatient 24 h series cortisol and adrenocorticotropic hormone (ACTH) measures. Data were analyzed for 3 daytime lags (7 Am-4 Pm, 4 Pm-10pm, 10 Pm-7 Am) corresponding to the hydrocortisone dosing period with cortisol and ACTH measured before the hydrocortisone dose.
Results:
Eleven participants completed at least 1 CGM session, and 7 out of 11 underwent both the CGM session and the cortisol/ACTH serial measures. In the whole cohort, the percentage of time of sensor glucose values <70 mg/dL was higher during the 10 Pm-7 Am and the 7 Am-4 Pm time slots than in the late afternoon period (17% [7, 54] and 15% [6.8, 24] vs 2% [1.1, 16.7] during the periods 7 Am-4 Pm and 4 Pm-10 Pm, respectively [P = .006 and P = .003]). Nighttime hypoglycemia was mostly spent below the 65 mg/dL (10.9% [4.1, 34]). The glycemic pattern paralleled the nadir of daily cortisol at 7 Am (10.3±4.4 μg/dL). A greater percentage of time in hypoglycemia was associated with lower cortisol concentration at 7 Am and 10 Pm (P < .001 and P = .005).
Conclusions:
Continuous glucose monitoring demonstrated a disrupted daily glucose pattern in children with CAH, paralleled by a lower cortisol concentration.
Clinicaltrials.Gov Registration:
NCT04322435.
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