SAT-261 Prospective Study of the Association between Early Adrenarche and Cognitive Function in Children with Cushing Disease

Abstract

Background: Previously, we reported a decline in cognitive scores of children with endogenous Cushing syndrome (CS); however, the generalizability of the findings is limited due to the small sample size. The present study investigated the relationship between change in cognitive scores prior to and one-year post transsphenoidal surgery, with age at initial presentation, duration of illness, and history of premature adrenarche (PA) as covariates. Both cortisol and adrenal androgens have key roles in the organizational and the maturational changes in brain structure and function during adolescence. Method: Prospective study of 41 children (17 females; 12 ±3 yr.) diagnosed with Cushing’s disease (CD), who completed diverse sets of cognitive measures prior to and one-year post-remission: (Wechsler Intelligence Scale for Children (WISC) or Wechsler Adult Intelligence Scale of Intelligence (WASI), Woodcock Johnson Psychoeducational Battery, California Verbal Learning, and Trail making tests. Linear regression of delta change in IQ test scores (from baseline to 1-year remission) with covariates of age, duration of illness, and history of premature adrenarche was used to analyze the data. Results: At baseline, children with CD had average to above average intelligence. Change in scores from baseline to 1-year remission was significant for performance IQ (PIQ), verbal IQ (VIQ), full IQ (FIQ), subsets: information, similarities, arithmetic, vocabulary, coding, and block design (p<0.01). Younger age at baseline with a history of PA was associated with a greater decrement in scores PIQ VIQ FIQ, coding, and block design(p<0.01). At baseline, serum DHEAS levels were discordant with pubertal stage in subjects <14yrs age; this discrepancy resolved at 1-yr remission. Conclusion: Younger age at baseline was a predictor of decrement in all summary IQ measures and some subset measures (picture completion, coding, & block design, arithmetic), (p < 0.01). Older age at presentation was associated with less of a decline in cognitive function measures, which suggests that after a return to eucortisolemia, the response of older adolescents is more similar to adult CD patients. At baseline, younger children with CD had DHEAS levels discordant with pubertal stage and were more likely to experience cognitive decrement after remission, suggesting that timing of adrenarche is an important moderator of cognitive function in children with CD.