Pathophysiology
Clinical meaning
Acromegaly results from chronic excess secretion of growth hormone (GH) in adults after epiphyseal plate closure. In over 95% of cases, the source is a GH-secreting pituitary adenoma (somatotroph adenoma) in the anterior pituitary gland. GH stimulates the liver to produce insulin-like growth factor 1 (IGF-1), the primary mediator of GH's tissue effects. IGF-1 promotes proliferation of bone, cartilage, soft tissue, and visceral organs. Because growth plates have fused in adults, GH excess cannot increase height - instead, it causes periosteal bone apposition (widening and thickening) of the hands, feet, jaw (prognathism), and skull, along with soft tissue hypertrophy of the tongue (macroglossia), skin, and internal organs (organomegaly). Cardiovascular complications are the leading cause of death: GH/IGF-1 excess causes cardiomyopathy (biventricular hypertrophy), accelerated atherosclerosis, and hypertension. Metabolic effects include insulin resistance and diabetes mellitus (GH is a counter-regulatory hormone that antagonizes insulin action at skeletal muscle and liver). The pituitary adenoma itself may cause mass effect symptoms: compression of the optic chiasm (bitemporal hemianopia), headaches, and hypopituitarism from destruction of surrounding normal pituitary tissue.