Current Advances in the Diagnosis and Management of Acromegaly

Abstract

Acromegaly is a rare endocrine disorder caused predominantly by growth hormone (GH)–secreting pituitary adenomas and is associated with substantial cardiometabolic, skeletal, and neoplastic morbidity. Despite advances in clinical care, diagnosis is frequently delayed owing to the insidious onset of symptoms, underscoring the need for improved detection strategies. This Review synthesizes recent progress in the diagnostic, therapeutic, and molecular characterization of acromegaly, highlighting how these advances are reshaping clinical management. Contemporary diagnosis centers on age-adjusted measurement of serum insulin-like growth factor-1, confirmatory GH suppression testing, and high-resolution pituitary magnetic resonance imaging. Beyond conventional diagnostics, molecular and genomic profiling, enabled by next-generation sequencing, has expanded understanding of the genetic landscape of GH-secreting adenomas, including alterations in GNAS, AIP, and other tumor suppressor and signaling pathway genes that influence tumor behavior, treatment response, and prognosis.

Management has evolved toward a precision-based, multimodal paradigm, with transsphenoidal surgery as first-line therapy, complemented by an expanding pharmacological armamentarium that includes long-acting somatostatin receptor ligands, GH receptor antagonists, dopamine agonists, and newer second-generation and oral agents. Emerging experimental approaches, such as targeted modulation of GH-secreting pathways and exploratory gene-editing strategies, hold promise for refractory disease, although their clinical application remains investigational. Together, these developments illustrate a shift toward integrated clinical and molecular frameworks that aim to enable earlier diagnosis, individualized therapy, and improved long-term outcomes for patients with acromegaly.