Quantitative Brain MRI in Congenital Adrenal Hyperplasia: In Vivo Assessment of the Cognitive and Structural Impact of Steroid Hormones.

Context: Brain white matter hyperintensities are seen on routine clinical imaging in 46% of adults with congenital adrenal hyperplasia (CAH). The extent and functional relevance of these abnormalities have not been studied with quantitative magnetic resonance imaging (MRI) analysis. Objective: To examine white matter microstructure, neural volumes, and central nervous system (CNS) metabolites in CAH due to 21-hydroxylase deficiency (21OHD) and to determine whether identified abnormalities are associated with cognition, glucocorticoid, and androgen exposure. Design, Setting, and Participants: A cross-sectional study at a tertiary hospital including 19 women (18 to 50 years) with 21OHD and 19 age-matched healthy women. Main Outcome Measure: Recruits underwent cognitive assessment and brain imaging, including diffusion weighted imaging of white matter, T1-weighted volumetry, and magnetic resonance spectroscopy for neural metabolites. We evaluated white matter microstructure by using tract-based spatial statistics. We compared cognitive scores, neural volumes, and metabolites between groups and relationships between glucocorticoid exposure, MRI, and neurologic outcomes. Results: Patients with 21OHD had widespread reductions in white matter structural integrity, reduced volumes of right hippocampus, bilateral thalami, cerebellum, and brainstem, and reduced mesial temporal lobe total choline content. Working memory, processing speed, and digit span and matrix reasoning scores were reduced in patients with 21OHD, despite similar education and intelligence to controls. Patients with 21OHD exposed to higher glucocorticoid doses had greater abnormalities in white matter microstructure and cognitive performance. Conclusion: We demonstrate that 21OHD and current glucocorticoid replacement regimens have a profound impact on brain morphology and function. If reversible, these CNS markers are a potential target for treatment.

Clinical characteristics and management of cranial diabetes insipidus in infants.

AIM: Cranial diabetes insipidus (CDI) is rare in infants with no guidelines on its management. We describe the first case series, characterizing the clinical features and treatment challenges. METHOD: Retrospective case note review of infants diagnosed with CDI between April 1992 and February 2011. RESULTS: Nineteen infants (52% male) were identified. Eight were born preterm. Median (range) age at diagnosis was 24 days (5-300); preterm babies were younger at diagnosis (21 vs. 46 days). In 58% (11/19) of infants, hypernatraemia was discovered incidentally. In 37% of cases there was associated midline anomalies, however, only four patients (21%) had absent posterior pituitary signal on a magnetic resonance imaging brain scan. The most frequent (5/19) underlying diagnosis was septo-optic dysplasia. Eight patients had isolated CDI and 11 had multiple pituitary hormone deficiencies. Isolated CDI tended to be more common in preterm, compared to term babies (p=0.11). Des-amino arginine vasopressin (DDAVP) was administered intranasally in eight and orally in 11 infants. Plasma sodium nadir following DDAVP administration was lower following intranasal compared to an oral route of administration (median: 128 vs. 133 mmol/L, p=0.022). No cases resolved on follow-up. CONCLUSIONS: CDI in infants is often diagnosed incidentally. Aetiology, clinical, and imaging features are very variable, with some differences between preterm and term infants. Oral DDAVP appears to be superior to intranasal with less pronounced serum sodium fluctuations.

ThOMAs: the other means of assessment.

We describe a pilot study to investigate whether drawing "Thomas the Tank Engine" could be as effective a measure of developmental progress as the Goodenough-Harris Draw A Man test against the ThOMAs test (The Other Means of Assessment), with internal validation. The study included 95 children aged between 3 and 11 years of age, including a subgroup of 13 children with registered special needs from community and general pediatric clinics within Birmingham, UK, as a means of validation. There was no significant evidence that ThOMAS was either culturally or sex biased. Using regression analysis, nine items were found to correlate highly with actual age, and their total score gave a correlation of 0.563 with age. Adding further items did not increase this. After being converted into age-standardized scores, ThOMAS was as sensitive and specific as the Draw A Man test, and more so above a defined age-standardized threshold. This pilot study suggests that drawing Thomas the Tank Engine would appear to be as sensitive and specific a means of identifying children with special needs as the Goodenough-Harris Draw A Man test. The relatively small sample size means that further research is necessary to further define the age standardizations and to refine the ThOMAs test.