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Impaired Cognitive Function in Congential Adrenal Hyperplasia« Back to Volume 22, Issue 3, September 2006 - Table of Contents Cognitive function in individuals with congential adrenal hyperplasia (CAH) is a topic of considerable interest. Effects of the condition or its treatment on cognitive function are plausible, ie, a permanent influence of sex steroid hormones in utero on brain development, the genetics of CAH or allied alleles, or the effects of under- or over-treatment with glucocorticoids during early postnatal period. Johannsen and colleagues conducted a case-control study of cognitive function in adult women with CAH. Participants included 35 women (84% of the eligible sample) diagnosed with CAH between 1953 and 2003 at a university hospital in Denmark. The patients with CYP21 mutations were grouped into salt wasters (SWs; n = 19, mean age, 31.2 yr; range, 19–46 yr), simple virilizers (SVs; n = 6, 34.6 yr, 23–51), late-onset (LO) CAH (n = 5, 25.5 yr, 19–36) and a mixed group of patients (mixed; n = 5, 28.8 yr, 17–49) with steroidogenic acute regulatory protein (StAR) deficiency (n = 3), CYP21 deficiency diagnosed in adolescence (n = 1), and 17-hydroxylase deficiency (n = 1). Patients with CYP21 deficiency were categorized by mutation severity, salt-wasting status, and clinical presentation. Control group participants were recruited through a general population registry of women born in the same month and year as the patient (response rate = 38%). The woman with the closest match on education was selected for pair-wise matching with the index patient. All participants received a medical interview, physical examination, psychological interview, cognitive assessment, hormone analyses and personality, sexual, and social functioning questionnaires. Five subtests (3 of 6 Verbal and 2 of 5 Performance) from the Wechsler Adult Intelligence Scale (WAIS) provided 3 indices of intelligence (IQ): full-scale IQs (FSIQ), performance (PIQ), and verbal (VIQ). (WAIS IQ scores are defined to yield a population mean of 100 [SD = 15].) Examiners were not blinded with respect to patients’ diagnoses. The combined CAH patient group achieved significantly lower FSIQ (84.5 vs 99.1), VIQ (86.6 vs 97.3) and PIQ scores (85.7 vs 101.3) than the pair-matched control group (Table). The same pattern was true for the SW subgroup. The LO patients also achieved significantly lower FSIQ and VIQ scores than matched controls. Further, the mixed group received significantly lower scores than controls on all IQ indices. In contrast, the SV subgroup was not statistically different from control participants. The SW group received significantly lower FSIQ and VIQ than the SV group, and a nonsignificant trend was observed for PIQ. Patients with verified hyponatremic crises (n = 14) vs all other CAH patients (n = 21) revealed significantly lower FSIQ (78.6 vs 88.4) and VIQ (79.9 vs 91.0), but not PIQ (82.9 vs 87.6). Editor’s CommentPediatric endocrinologists have traditionally been taught that cognitive function and IQ in patients with CAH are not usually sources of concern. This study, and others,1,2 suggest the contrary: individuals with CAH, particularly the SW-variant, are at risk for lower IQ. Elevated prenatal androgen exposure may affect later patterns of cognitive development and cerebral lateralization, thus individuals with CAH may exhibit a male-typical pattern of cognitive strengths and hemispheric lateralization,3-5 although other research challenges this conclusion.6 This paper underscores the importance of partitioning the sample in data analyses according to genetic mutation and clinical sequelae. In particular, those individuals who had suffered multiple hyponatremic episodes should be considered a particularly high-risk group for neuropsychological sequelae. Although these investigators grouped CAH participants into categories according to corticosteroid replacement dose, it is puzzling that accompanying analyses were not reported. Nevertheless, the authors noted that glucocorticoids are important for normal maturation of the developing central nervous system and that excessive doses in infancy (reduced in current treatment recommendations7) might be partially responsible for the pattern of intellectual deficits observed in this cohort. This study and corroborating findings underscore the importance of surveilling cognitive function among children born with CAH. To this condition, one could add Turner, Noonan, and Klinefelter syndromes, congenital hypothyroidism, children born small for gestational age, early-onset diabetes, and many others who frequent pediatric endocrinology clinics. Forging collaborations between pediatric endocrinology and hospital-based pediatric psychology or child psychiatry programs that can offer neuropsychological evaluations would likely spare many youths (and their families) needless academic failure and frustration. David E. Sandberg, PhD References - (linked to
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Volume 25 Number 1
June 2009
www.GGHjournal.com
ISSN 1932-9032
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