Prescribed hydrocortisone dose shrinks with weight gain in congenital adrenal hyperplasia
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Clinicians are prescribing children with congenital adrenal hyperplasia decreasing dosages of hydrocortisone per body surface area as weight and BMI increase, without worse treatment outcomes, according to study data.
In a retrospective analysis of data from the International Congenital Adrenal Hyperplasia Registry, researchers found large variability in 17-hydroxyprogesterone (17‐OH progesterone) and androstenedione levels between different centers. While neither biomarker varied by hydrocortisone dose or weight, multivariate linear mixed-effects models analysis revealed hydrocortisone dosage was associated with both weight and BMI standard deviation scores.
“Children with increasing weight and BMI standard deviation score are being prescribed less glucocorticoid dose per body surface area,” Nils Krone, MD, FRCPCH, professor of pediatric endocrinology and honorary consultant pediatric endocrinologist in the department of oncology and metabolism at University of Sheffield in the U.K., and colleagues wrote. “Assessment of biochemical markers within this relationship has not shown a clear detriment to their disease control, although this warrants further investigation in relation to a more holistic assessment of control.”
Researchers collected data from 345 children and adolescents aged 18 years and younger with a diagnosis of 21‐hydroxylase deficiency who were treated with oral hydrocortisone as a glucocorticoid replacement and cared for at 21 centers in 14 countries (52.2% girls; median age, 4.3 years). Clinic visits taking place from January 2000 to October 2020 were included. Serum 17‐OH progesterone and androstenedione concentrations, height and weight, data on the most recent hydrocortisone dose and serum biomarkers were collected. Measures were assessed using linear mixed-effects models.
Participants were prescribed a median hydrocortisone dose of 11.3 mg/m2 per day. The median 17‐OH progesterone concentration was 35.7 nmol/L, and the median androstenedione level was 0 nmol//L. Children younger than 12 years had a lower median 17‐OH progesterone level (29 nmol/L vs. 60.5 nmol/L) and a lower median androstenedione level (0 nmol/L vs. 10.5 nmol/L) than youth aged 12 years and older (P < .001 for both).
Centers with more than 10 readings available had differences in median 17‐OH progesterone, ranging from 2 nmol/L to 104.4 nmol/L (P < .001). There was no significant difference in the variance of median androstenedione concentrations. There was a significant correlation between 17‐OH progesterone and androstenedione in children younger than 12 years (R2 = 0.24; P < .001).
Of the cohort, 308 children with full biomarker and dose data available were included in cohort modeling. After adjusting for multiple variables, researchers found the relationship between dose decreasing with age was due to the confounding effect of increasing weight standard deviation score with age. Every 1-point increase in weight standard deviation score was associated with a decrease in hydrocortisone dose per body surface area of 1.02 mg/m2 per day, and every 1-point increase in BMI standard deviation score was associated with a decrease in hydrocortisone dose per body surface area of 0.47 mg/m2 per day.
“[Hydrocortisone] dose should be regularly reviewed taking into consideration their growth, pubertal development, biomarkers, side effects of treatment and compliance,” the researchers wrote. “Standard biomarker measurement practices are needed to evaluate biochemical evidence of disease control. Collection of real-world data within the established International Congenital Adrenal Hyperplasia platform is to be encouraged and will allow us to gain further insights into patients as they progress through puberty, helping to improve patient care and reducing unwarranted variation in practice.”
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