Metabolic, Cardiovascular, and Cerebrovascular Outcomes in Growth Hormone-Deficient Subjects with Previous Cushing’s Disease or Non-Functioning Pituitary Adenoma

Abstract

Previous exposure to hypercortisolism due to Cushing's disease (CD) may adversely affect long-term metabolic and cardiovascular outcomes. In particular, metabolic and cardiovascular outcomes of patients with previous CD who require GH replacement have not been fully established. The aim of the study was to compare the prevalence and incidence of metabolic syndrome (Adult Treatment Panel III criteria), diabetes mellitus, cardiovascular disease, and cerebrovascular disease in GH-treated subjects with previous CD with GH-treated subjects with previous nonfunctioning pituitary adenoma (NFPA). We conducted post hoc analysis of the observational Hypopituitary Control and Complications Study conducted at 362 international centers (1995-2006). We studied adult-onset GH-deficient subjects with previous CD (n = 160) or NFPA (n = 879). All subjects received GH replacement therapy and were GH naive at enrollment. Multiple pituitary deficits were prevalent in both groups. We measured the prevalence and incidence of metabolic syndrome, diabetes mellitus, cardiovascular disease, and cerebrovascular disease at baseline and at 3 yr, standardized for age and sex differences between groups. Compared with subjects with previous NFPA, subjects with previous CD had a significantly greater 3-yr incidence of metabolic syndrome (CD, 23.4%; NFPA, 9.2%; P = 0.01), baseline (CD, 6.3%; NFPA, 2.2%; P < 0.01) and 3-yr (CD, 7.6%; NFPA, 3.9%; P = 0.04) prevalence of cardiovascular disease, and baseline (CD, 6.4%; NFPA, 1.8%; P = 0.03) and 3-yr (CD, 10.2%; NFPA, 2.9%; P = 0.01) prevalence of cerebrovascular disease. Previous hypercortisolism may predispose GH-treated, GH-deficient subjects with prior CD to an increased risk of metabolic syndrome, cardiovascular disease, and cerebrovascular disease.