SAN FRANCISCO – Administering daily hydrocortisone prescriptions in four divided doses, instead of three, can improve control of congenital adrenal hyperplasia and obviate the need for additional steroids, British researchers found in a retrospective cross-sectional study.
A decade ago, it was assumed that children with poorly controlled moderate-to-severe disease "needed higher doses rather than more frequent dosing; if patients were not controlled on three-times-a-day dosing, we’d increase the dose. Now, we go four times a day, and don’t necessarily have to increase the dose. We see better control with QID dosing," said lead investigator Dr. Anbezhil Subbarayan, a pediatric endocrinologist at Great Ormond Street Hospital for Children in London.
Dr. Anbezhil Subbarayan
His team compared 107 children under treatment there with a similar cohort treated a decade ago and found that the approach led to a reduction in mean daily hydrocortisone doses from 17.5 mg/m2 to 13.3 mg/m2 and a drop in mean daily doses of 9 alpha-fludrocortisone, administered in one or two divided doses, from 112 mcg/m2 to 102 mcg/m2.
That led to a corresponding drop in the prevalence of steroid-induced systolic hypertension from 58% of patients to 21%; a drop in diastolic hypertension prevalence from 24% to 9%; and improvement in mean body mass index standard deviation scores (BMI-SDS) from 1.57 to 0.98. The results were also published online(Clin. Endocrinol [Oxf] 2013 [doi:10.1111/cen.12265]).
"Our message" is that "patients under poor control should [try] four-times-a-day" hydrocortisone dosing. With a half-life of just 4-6 hours, spacing out hydrocortisone administration "should improve control in patients with moderate-to-severe disease without increasing the need for steroids, which can worsen cardiovascular risk factors," Dr. Subbarayan said at the Endocrine Society’s annual meeting.
"Ideally, the first hydrocortisone dose should be given at 4:00 a.m. Some parents are motivated" to do that; for those who find it impractical, "we try to encourage giving hydrocortisone first thing in the morning, maybe at 6:00 a.m." For children with mild disease, divided doses three times a day might be enough, he said.
Despite reduced steroid doses and cardiovascular risk factors, obesity and systolic hypertension remain problematic in kids with congenital adrenal hyperplasia.
The team found that 24% of their children were obese (BMI-SDS greater than 2), and that BMI-SD scores were significantly higher, compared with British children overall. The mean systolic blood pressure of 108 mm Hg (SD 13.5) was higher, as well. Differences in diastolic pressure did not reach statistical significance.
The values were assessed during annual reviews when the children were admitted to the hospital for 24 hours for serial monitoring of cortisol levels and clinical parameters, and dose adjustments. The median age in the study was 9.2 years; 64% were girls.
The authors said they have no disclosures.