Brain White Matter Abnormality in a Newborn Infant with Congenital Adrenal Hyperplasia

Abstract

Several studies have described brain white matter abnormalities on magnetic resonance imaging (MRI) in children and adults with congenital adrenal hyperplasia (CAH), while the brain MRI findings of newborn infants with CAH have not been clarified. We report a newborn boy with CAH who presented brain white matter abnormality on MRI. He was diagnosed as having salt-wasting CAH with a high 17-OHP level at neonatal screening and was initially treated with hydrocortisone at 8 days of age. On day 11 after birth, he had a generalized tonic seizure. No evidence of serum electrolyte abnormalities was observed. Brain MRI revealed white matter abnormalities that consisted of bilateral small diffuse hyperintensities on T1-weighted images with slightly low intensity on T2-weighted images in the watershed area. Several factors associated with brain white matter abnormalities in adults with CAH, such as increasing age, hypertension, diabetes and corticosteroid replacement, were not applicable. Although the cause of the phenomenon in this case is unclear, brain white matter abnormality could be observed in newborn infants with CAH as well as in adult patients.

Effects of chromosomal sex and hormonal influences on shaping sex differences in brain and behavior: Lessons from cases of disorders of sex development

“…Another brain structural metric that has been assessed in XX and XY individuals with CAH is abnormalities in white matter distributions. MRI studies of adult patients with salt‐wasting, simple virilizing, and even nonclassical congenital adrenal hyperplasia have established white matter hyperintensities in various brain regions (Sinforiani et al, ; Nass et al, ; Kaga et al, ; Mnif et al, ; Winfeld et al, ). Areas of the brain that seem to be most frequently affected in CAH patients are the periventricular regions and areas of the cerebellum and the corpus callosum.…”

“…It has also been proposed that the imbalance of hormones during development contributes to improper oligodendrocyte differentiation and improper myelination (Bergamaschi et al, ). In addition to adult studies, there have been several documented cases of newborns with CAH exhibiting white matter anomalies (Kaga et al, ; Winfeld et al, ). Although it does appear that replacement therapies over a long time frame may affect white matter, findings in newborns with CAH raise the notion that long‐term glucocorticoid replacement therapies may not be the sole explanation for the disturbances in white matter.…”

Adrenal Disorders and the Paediatric Brain: Pathophysiological Considerations and Clinical Implications

“…Of note, several studies based on MRI have described brain white matter abnormalities in children with CAH, with the radiological changes that can be sometimes detected from the first days of life in children with classic CAH [ 49 , 55 ]. In addition to the white matter changes, moderate atrophy in the right temporal cortex, small volume hippocampus, and agenesis or thinning of the corpus callosum were observed in the long term follow-up of children with classic CAH [ 56 – 58 ].…”

“…Clinically, these children may present with seizures, lethargy, postural and intentional tremor, tendon reflex asymmetry, or cerebellar symptoms [ 49 , 55 – 58 ]. Standard MRI sequences performed in the first days of life in some newborns with classical CAH typically showed diffuse hyperintensity on T1-weighted sequences ( Figure 2(a) ), with reduced diffusion in the periventricular white matter on the diffusion-weighted imaging (DWI) sequences.…”

“…At 1 yr. of age, bilateral small diffuse hyperintensities are documented (white arrow) on T1-weighted images (b). (Reprinted with permission from [ 49 ], Copyright Japanese Society for Pediatric Endocrinology).…”