The Spectrum of GH Excess in Carney Complex and Genotype-phenotype Correlations

Area of Science:

• Endocrinology
• Genetics
• Neoplasia Syndromes

Background:

• Carney complex (CNC) is a rare familial neoplasia syndrome.
• Growth hormone excess (GHE) is a known complication of CNC.

Purpose of the Study:

• To determine the frequency of GHE in a large cohort of CNC patients.
• To identify genotype-phenotype correlations related to GHE in CNC.

Main Methods:

• Retrospective analysis of 140 CNC patients with biochemical GH secretion evaluation.
• GHE diagnosis based on IGF-1 levels, GH suppression/stimulation tests, and overnight GH secretion.
• Analysis of PRKAR1A gene variants and pituitary imaging findings.

Main Results:

• GHE was present in 35.7% of patients; symptomatic acromegaly in 20%.
• PRKAR1A gene defects were found in 99.3% of patients.
• Specific PRKAR1A variants (null expression, c.491_492delTG) and abnormal pituitary imaging significantly increased GHE risk.

Conclusions:

• GH secretion dysregulation is a frequent occurrence in Carney complex.
• Understanding the clinical, genetic, and imaging spectrum facilitates earlier diagnosis and improved management of GHE in CNC.