Neonatal Cushing Syndrome: A Rare but Potentially Devastating Disease

Area of Science:

• Pediatric Endocrinology
• Oncology
• Genetics

Background:

• Neonatal Cushing syndrome (CS) is primarily caused by exogenous glucocorticoids, but endogenous causes, particularly adrenal lesions, are significant in infants.
• Adrenocortical tumors (ACTs) are the most frequent source of endogenous neonatal CS, often associated with TP53 gene mutations and Li-Fraumeni syndrome.
• Other rare causes include McCune-Albright syndrome and Beckwith-Wiedemann syndrome, highlighting the diverse etiology of this condition.

Purpose of the Study:

• To summarize the causes, associations, and management of neonatal Cushing syndrome.
• To emphasize the role of adrenocortical tumors and genetic syndromes in endogenous neonatal CS.
• To discuss the persistent manifestations of CS after treatment.

Main Methods:

• Review of existing literature on neonatal Cushing syndrome.
• Analysis of common and rare etiologies, including genetic predispositions.
• Summary of current management strategies and outcomes.

Main Results:

• Exogenous glucocorticoids are the most common cause of neonatal CS.
• Adrenocortical tumors (ACTs), frequently linked to TP53 mutations and Li-Fraumeni syndrome, are the leading cause of endogenous neonatal CS.
• Syndromic associations like McCune-Albright and Beckwith-Wiedemann syndromes are less common causes.

Conclusions:

• Adrenocortical tumors are the primary driver of endogenous neonatal Cushing syndrome, often with underlying genetic mutations.
• While surgical resection is the mainstay of treatment, persistent clinical manifestations highlight the complexity of managing neonatal CS.
• Further research into genetic factors and long-term outcomes is warranted.