Acromegaly is a rare, chronic endocrine disorder characterized by prolonged exposure to excessive growth hormone (GH) and insulin-like growth factor-1 (IGF-1), most commonly resulting from a GH-secreting pituitary adenoma. Despite its insidious onset, acromegaly is associated with substantial morbidity and increased mortality, primarily due to cardiovascular, metabolic, respiratory, and neoplastic complications. A delayed diagnosis remains a major clinical challenge, as early manifestations are often subtle and progress slowly over years.The etiopathogenesis of acromegaly involves dysregulation of the hypothalamic–pituitary–somatic axis, leading to autonomous GH secretion and subsequent elevation of circulating IGF-1. At the molecular level, somatic mutations, particularly in the GNAS gene, play a crucial role in pituitary adenoma development and hormonal hypersecretion. Persistent activation of GH and IGF-1 signaling pathways induces widespread anabolic, mitogenic, and anti-apoptotic effects, resulting in tissue overgrowth, organomegaly, and structural remodeling of multiple organ systems.Clinically, acromegaly presents with a broad spectrum of manifestations affecting the musculoskeletal, cardiovascular, respiratory, metabolic, and neurological systems. Characteristic phenotypic features include acral enlargement, facial dysmorphism, and soft tissue hypertrophy, while systemic complications such as cardiomyopathy, arterial hypertension, insulin resistance, type 2 diabetes mellitus, obstructive sleep apnea, and increased risk of malignancies significantly contribute to disease burden. The heterogeneity of clinical presentation underscores the importance of a multidisciplinary approach to diagnosis and management.

This review provides a comprehensive overview of the etiopathogenetic mechanisms underlying acromegaly and highlights the systemic nature of its clinical manifestations. A deeper understanding of the pathophysiological processes involved is essential for early recognition, risk stratification, and optimization of therapeutic strategies aimed at reducing long-term complications and improving patient outcomes.

Acromegaly; Growth hormone; Insulin-like growth factor-1; Pituitary adenoma; GH–IGF-1 axis; Clinical manifestations; Multisystem complications

Drewes AM, Arlien-Søborg MC, Lunde Jørgensen JO, Jensen MP. [Acromegaly and symptoms of the motor apparatus]. Ugeskr Laeger. 2018 Nov 12;180(46)

Pazarlı AC, Köseoğlu Hİ, Kutlutürk F, Gökçe E. Association of Acromegaly and Central Sleep Apnea Syndrome. Turk Thorac J. 2019 Apr;20(2):157-159

Postma MR, Wolters TLC, van den Berg G, van Herwaarden AE, Muller Kobold AC, Sluiter WJ, Wagenmakers MA, van den Bergh ACM, Wolffenbuttel BHR, Hermus ARMM, Netea-Maier RT, van Beek AP. Postoperative use of somatostatin analogs and mortality in patients with acromegaly. Eur J Endocrinol. 2019 Jan 01;180(1):1-9.

Vilar L, Vilar CF, Lyra R, Lyra R, Naves LA. Acromegaly: clinical features at diagnosis. Pituitary. 2017 Feb;20(1):22-32.

Vallar L, Spada A, Giannattasio G. Altered Gs and adenylate cyclase activity in human GH-secreting pituitary adenomas. Nature. 1987 Dec 10-16;330(6148):566-8.

Bogusławska A, Korbonits M. Genetics of Acromegaly and Gigantism. J Clin Med. 2021 Mar 29;10(7)

Melmed S. Acromegaly. N Engl J Med. 1990 Apr 05;322(14):966-77.

Esposito D, Ragnarsson O, Johannsson G, Olsson DS. Incidence of Benign and Malignant Tumors in Patients With Acromegaly Is Increased: A Nationwide Population-based Study. J Clin Endocrinol Metab. 2021 Nov 19;106(12):3487-3496.

Matyjaszek-Matuszek B, Obel E, Lewicki M, Kowalczyk-Bołtuć J, Smoleń A. Prevalence of neoplasms in patients with acromegaly - the need for a national registry. Ann Agric Environ Med. 2018 Sep 25;25(3):559-561.

Sharma AN, Tan M, Amsterdam EA, Singh GD. Acromegalic cardiomyopathy: Epidemiology, diagnosis, and management. Clin Cardiol. 2018 Mar;41(3):419-425.