The spectrum of growth hormone excess in Carney complex and genotype-phenotype correlations.

Context: Carney complex (CNC) is a familial neoplasia syndrome associated with growth hormone (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 one biochemical evaluation of GH secretion at our center from 1995-2021 (n=140) were included in the study. Diagnosis of GHE was based on levels of insulin-like growth factor-1 (IGF-1), GH suppression during oral glucose tolerance test (OGTT), GH stimulation after thyrotropin (TRH) 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 Intervals (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 an abnormal pituitary imaging had 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. The clinical spectrum of this disorder and its association with genetic and imaging characteristics of the patient make prompt diagnosis and management more successful.