Nonmalignant Adrenocorticotrophic Hormone-Independent Cushing's Syndrome in Pediatric Patients: A Retrospective Observational Cohort Study

Abstract

Introduction: Adrenocorticotrophic hormone (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 and 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, 7 had MCAS, 7 had primary pigmented nodular adrenocortical disease (PPNAD) as part of CNC (Carney complex), and 1 had CS with no etiology found. Age at CS diagnosis was 0.3 years 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 7 MCAS patients had learning disabilities vs. only 2 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 hormone therapy. At the 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.

Conclusion: 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.

Keywords: Carney complex; Cushing’s syndrome; Growth; McCune-Albright syndrome.