Early adrenal activation in boys with Cystic Fibrosis may explain impaired final height

Background
BMI increase in early childhood was found to be a contributing factor for impaired final height in boys with Cystic Fibrosis (CF). This may be explained by early adrenarche triggering an accelerated bone maturation resulting in a compromised growth spurt during puberty. In healthy Dutch boys and girls, adrenarche starts from the age of 9 and 8 yrs with DHEAS > 1 µmol/L respectively.

Aim
To analyse the timing of adrenarche in boys with CF, to associate early BMI increase to timing of adrenarche and to analyse differences in DHEAS-levels between boys and girls.  

Methods
Since 2018, anthropomorphic, pubertal and endocrine data were collected in children with CF. Early adrenal activation in boys was defined as a DHEAS ≥ 1 µmol/L before the age of 9 years.

Results
Thirteen boys (mean age 8.55 ± 0.27 yrs) and 13 girls (mean age 8.52 ± 0.31 yrs) were enrolled until June 2022. The median (range) DHEAS level was 1.3 µmol/L (0.40 – 6.30) and 0.96 µmol/L (0.25 – 1.80) in boys and girls respectively (p = 0.199). Eight boys (61.5%) had an early rise in DHEAS-levels ≥ 1 µmol/L (i.e. before the age of 9 years). Five out of 11 boys (45.5%) and 4 out of 8 girls (50%) had a mean accelerated bone-age of 1.55 ± 0.97 and 0.75 ± 0.96 yrs respectively.
The mean difference between chronological age and bone-age was more pronounced in boys and girls with DHEAS-levels ≥1 µmol/L (Δ0.65 ± 1.47 (n=8) and Δ0.75 ± 0.72 yrs (n=4)) in comparison to boys and girls with DHEAS-level <1 µmol/L (Δ-0.91 ± 0.29 (n=3) and Δ-0.25 ± 0.21 respectively (p = 0.11 and p = 0.036). A moderate, significant correlation was found between the ΔBMI-SDS and DHEAS-levels between 1-6 years (r=0.653, p = 0.029) in boys. This relationship was absent in girls.

Conclusion
In this small cohort, 61.5 % of boys with CF between 8-9 years had an early rise of DHEAS, which could be correlated to ΔBMI-SDS between 1-6 years in boys only. Therefore, early adrenal activation may be one of the factors contributing to early and suboptimal growth during puberty and impaired final height in boys with CF.