Association Between Biochemical Control and Comorbidities and Symptoms Among Patients with Acromegaly in Italy: Stratified Analyses by Age and Gender

Acromegaly is characterized by overproduction of growth hormone (GH) and elevated insulin-like growth factor-1 (IGF-1). This is the first study characterizing the long-term association between GH/IGF-1 normalization (biochemical control) and comorbidities/symptoms in a real-world setting stratified by demographic characteristics. Medical records for adult acromegaly patients with ≥6 months of follow-up at an Italian endocrinology center were reviewed. Patients were followed from first GH/IGF-1 measurement until onset of comorbidities/symptoms, loss to follow-up, or death. Biochemical control was assessed annually and defined as >50% days with IGF-1 measurements ≤upper limit of normal or GH measurements ≤2.5µg/L. Cox models were used to assess the association between biochemical control and onset of comorbidities/symptoms, stratified by age (<45 vs. ≥45 years at diagnosis) and gender. Comorbidities/symptoms assessed consisted of arthropathy, cancer, cardiovascular system disorders, cerebrovascular disease, colon polyps, endocrine/metabolic system disorders, and sleep apnea. All 150 eligible patients were Caucasian and 47% were female. Mean age at diagnosis was 43.1. Mean follow-up time was 8 years. When stratified by age, biochemical control was significantly associated with a reduced hazard of cardiovascular system disorders among patients <45 (hazard ratio [HR]=0.42, 95%CI=0.20-85) and diabetes among patients ≥45 (HR=0.23, 95%CI=0.07-0.77). Biochemical control was significantly associated with a higher hazard of unspecified arthropathy (HR=2.03, 95%CI=1.10-3.74) and hypertriglyceridemia (HR=2.31, 95%CI=1.00-5.33) among patients ≥45. When stratified by gender, biochemical control was significantly associated with a reduced hazard of cancer among men (HR=0.14, 95%CI=0.03-0.66) and glucose metabolism abnormalities and diabetes among women (HR=0.34, 95%CI=0.12-0.91; HR=0.14, 95%CI=0.03-0.61, respectively). Other associations stratified by age/gender were observed, but didn't reach significance. Biochemical control was associated with delayed onset of certain comorbidities/symptoms across all patient subgroups, particularly cardiovascular system disorders and diabetes, underscoring the long-term benefit of biochemical control that transcends age and gender differences, and importance of therapies targeting biochemical control.