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

Abstract

Abstract Context Carney complex (CNC) is a familial neoplasia syndrome associated with GH excess (GHE). Objective To describe the frequency of GHE in a large cohort of patients with CNC and to identify genotype-phenotype correlations. Methods Patients with CNC with at least 1 biochemical evaluation of GH secretion at our center from 1995 to 2021 (n = 140) were included in the study. Diagnosis of GHE was based on levels of IGF-1, GH suppression during oral glucose tolerance test, GH stimulation after thyrotropin administration and overnight GH secretion. Results Fifty patients (35.7%) had GHE, and 28 subjects (20%) had symptomatic acromegaly, with median age at diagnosis of 25.3 and 26.1 years, respectively. Most of the patients (99.3%) had a PRKAR1A gene defect. There was a higher risk of GHE in patients harboring a variant that led to no expression of the affected allele [hazard risk (HR): 3.06, 95% confidence interval (CI): 1.2-7.8] and for patients harboring the hotspot variant c.491_492delTG (HR: 2.10, 95% CI: 1.1-4.1). Almost half of patients with CNC had an abnormal finding on pituitary imaging. CNC patients with abnormal pituitary imaging had a higher risk of GHE (HR: 2.94, 95% CI: 1.5-5.8), especially when single or multiple adenoma-like lesions were identified. Management of patients with symptomatic acromegaly involved surgical and medical approaches. Conclusion Dysregulation of GH secretion is a common finding in CNC. Knowing the clinical spectrum of this disorder and its association with genetic and imaging characteristics of the patient make more likely its prompt diagnosis and better management.