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Infants with Congenital Adrenal Hyperplasia Exhibit Thalamic Discrepancies in Early Brain Structure
Vidya Rajagopalan1,2, Lloyd N Overholtzer3, William S Kim3
1Department of Radiology, Children's Hospital Los Angeles (CHLA), Los Angeles, California, USA.
Insights
Infants with congenital adrenal hyperplasia (CAH) show smaller thalamic volumes, indicating early brain development differences. These findings suggest prenatal influences on brain structure in CAH patients.
Area of Science:
- Neuroscience
- Developmental Biology
- Endocrinology
Background:
- Classical congenital adrenal hyperplasia (CAH) is characterized by prenatal and postnatal hormonal imbalances.
- Early life hormonal dysregulation in CAH may impact neurodevelopment.
- Understanding brain structure in infants with CAH is crucial for characterizing developmental trajectories.
Purpose of the Study:
- To investigate brain structure differences in infants with classical CAH compared to healthy controls.
- To identify specific brain regions affected by CAH during early development.
Main Methods:
- 16 infants with classical CAH and 14 control infants underwent 3-Tesla MRI.
- Regional brain volumes were analyzed, adjusting for post-conceptional age and sex.
- Regression and relaimpo analyses were used to compare brain region differentiation between groups.
Main Results:
- Infants with CAH exhibited significantly smaller thalamic volumes compared to controls (p=0.02).
- The temporal lobe was found to be larger in infants with CAH after adjusting for total brain volume (p=0.03).
- The thalamus (22%) and parietal lobe (10%) showed the most differentiation between CAH and control infants.
Conclusions:
- Infants with CAH display smaller thalamic regions early in life, suggesting prenatal developmental influences.
- The thalamus's early emergence makes it vulnerable to intrauterine environmental changes.
- Longitudinal studies are warranted to track brain development through adolescence in CAH patients.
Introduction:
Patients with classical congenital adrenal hyperplasia (CAH) have prenatal and postnatal hormonal imbalances. To characterize the ontogeny of reported brain and behavior changes in older children with CAH, we aimed to study the brain structure in infants with CAH compared to healthy controls.
Methods:
We performed neuroimaging in 16 infants with classical CAH due to 21-hydroxylase deficiency (8 males, gestational age 38.2 ± 1.7 weeks, post-conceptional age [PCA] 42.2 ± 3.0 weeks) and 14 control infants (9 males, gestational age 38.5 ± 1.8 weeks, PCA 42.5 ± 2.4 weeks) utilizing 3-Tesla magnetic resonance imaging. Regional brain volumes were adjusted for PCA and sex, along with an additional adjustment for total brain volume (TBV), for group comparisons by regression analyses (mean, 95% confidence interval [CI]). The degree to which each brain region was differentiated between CAH and control infants was examined by relaimpo analyses, adjusting for all other brain regions, PCA, and sex.
Results:
Infants with CAH had significantly smaller thalamic volumes (8,606 mm3, 95% CI [8,209, 9,002]) compared to age-matched control infants (9,215 mm3, 95% CI [8,783, 9,647]; β = -609; p = 0.02) which remained smaller after further adjustment for TBV. Upon further adjustment for TBV, the temporal lobe was larger in infants with CAH (66,817 mm3, CI [65,957, 67,677]) compared to controls (65,616 mm3, CI [64,680, 66,551]; β = 1,202, p = 0.03). The brain regions most differentiated between CAH versus controls were the thalamus (22%) and parietal lobe (10%).
Conclusions:
Infants with CAH exhibit smaller thalamic regions from early life, suggesting a prenatal influence on brain development in CAH. Thalamic emergence at 8-14 weeks makes the region particularly vulnerable to changes in the intrauterine environment, with potential implications for later maturing brain regions. These changes may take time to manifest, meriting longitudinal study through adolescence in CAH.
