Abstract
OBJECTIVE: Cushing syndrome (CS) often presents with obesity that is not as severe in children as it is in adults. The role of obesity in the severity of metabolic syndrome in children with CS has not been studied. This study evaluates whether pediatric patients with CS have obesity-specific differences in their demographic, biochemical, and presenting findings. DESIGN: Cohort study. PARTICIPANTS AND METHODS: We analyzed 273 patients with young onset of CS at ≤18 years old and who were classified as patients with or without obesity based on their BMI z scores. RESULTS: Patients without obesity (n = 84, 31%) were more frequently females with an older age of onset compared with patients with obesity (n = 189, 69%). Consistent with their older age, patients without obesity were also more likely to have advanced Tanner stages. Patients with and without obesity had a similar duration of disease, but patients with obesity showed higher markers of hypercortisolemia (urinary free cortisol, UFC). A higher prevalence of hypertension and insulin resistance was seen in patients with obesity than those without obesity, adjusting for UFC (P < .05 for all comparisons). While fatty liver disease was not statistically different among the entire cohort, elevated alanine transaminase and metabolic dysfunction-associated steatotic liver disease scores were more common in ACTH-dependent CS patients with obesity (P < .05). CONCLUSIONS: Weight gain appears to mediate some but not all the cortisol-associated complications in pediatric CS. Therefore, obesity may be a modifiable risk factor among these patients.