The effects of long-term growth hormone and insulin-like growth factor-1 exposure on the development of cardiovascular, cerebrovascular and metabolic co-morbidities in treated patients with acromegaly

Abstract

Acromegaly is characterized by the hypersecretion of growth hormone (GH) and insulin-like growth factor-1 (IGF-1). This leads to an increased cardiovascular, cerebrovascular and metabolic morbidity resulting in excess mortality. There is controversy over which biomarker, GH or IGF-1, better predicts this increased morbidity and mortality. The relationship between the cumulative exposure to GH and IGF-1 with co-morbidities in acromegaly has not previously been reported. To investigate the relationship between the cumulative exposure to GH and IGF-1 with cardiovascular, cerebrovascular and metabolic co-morbidities. Records of 116 acromegalic patients were retrospectively examined. Cardiovascular and cerebrovascular histories, serum GH and IGF-1, fasting glucose and oral glucose tolerance test results, were reviewed for the duration of follow-up. IGF-1 index was calculated by dividing each serum IGF-1 value by the upper limit of reference range for IGF-1. GH and IGF-1 burdens were calculated for each patient by multiplying known disease duration (in years) by mean level of basal GH or IGF-1 index recorded during the patients' entire follow-up. Patients with abnormal glucose tolerance had a significantly higher mean GH burden compared with euglycaemic patients (P = 0·005). Ischaemic heart disease was also associated with a higher GH burden (P = 0·009) whereas cerebrovascular disease and cardiomyopathy were associated with a significantly higher mean IGF-1 burden (P = 0·018, P = 0·011 respectively). This study identifies associations of raised GH and IGF-1 burden with cardiovascular, cerebrovascular and metabolic complications of acromegaly. Results from this study therefore suggest that consideration of the overall level of GH and IGF-1 exposure may provide important information for the management and surveillance of patients with treated acromegaly.