PURPOSE: ACTH-independent Cushing's syndrome (CS) is a rare cause of pediatric CS. Our objective was to describe the features of pediatric ACTH-independent CS and to compare groups defined by etiology.
METHODS: We conducted a retrospective observational study of patients aged 0-18 years at diagnosis between 1992-2022 for ACTH-independent CS in three Paris pediatric hospitals. Additionally, we compared the outcomes of McCune-Albright syndrome (MCAS) patients with CS and without CS.
RESULTS: Of the 15 patients with CS, seven had MCAS, seven primary pigmented nodular adrenocortical disease (PPNAD) as part of CNC (Carney complex), and one had CS with no etiology found. Age at CS diagnosis was 0,3 year old (0,17;1) in MCAS and 9 years old (5;15) in PPNAD. The MCAS group had more impaired growth retardation (-4,75 SDS in MCAS vs -1 SDS in CNC, p = 0,006) and higher prevalences of intrauterine growth retardation (P=0.01) and liver dysfunction at diagnosis (P=0.04). All seven MCAS patients had learning disabilities vs. only two CNC patients. 12 out of 15 had bilateral adrenalectomy. None of the MCAS patients received Growth hormone therapy, while 4 CNC patients benefited from growth hormon therapy. At end of follow up, growth recovered in both groups, albeit less in the MCAS group (-1,5 SDS in MCAS vs -0,5 SDS in CNC), in which liver dysfunction often persisted.
CONCLUSIONS: ACTH-independent CS is rare but can lead to significant burden in children. Early diagnosis and management are essential. New drugs targeting adrenal steroid synthesis are awaited.
