Acromegaly
Timely and effective treatment is crucial to managing symptoms.
Treatment improves quality of life and mitigates serious complications
To help reduce morbidity and mortality associated with acromegaly, early diagnosis and timely treatment, involving a multidisciplinary team, is critical.1,2 The negative effects associated with this disorder can be improved by achieving adequate biochemical and symptom control through various modalities, including a combination of surgical therapy, medical therapy, and radiotherapy.3-7
The goals of treatment for acromegaly include:1,2,8,9
- Biochemical remission (the primary assessment for treatment outcome)
- Maintaining serum IGF-1 levels in the mid to upper half of the age-related reference range to avoid GH deficiency
- Reduction of signs and symptoms
- Improve quality of life
- Reduction of co-morbidities
- Minimize long-term mortality risk
There are several approaches used to treat:1,8
Surgical intervention is considered to be the first-line treatment of choice for micro or macroadenomas. The goal of surgery is to remove pituitary tumors.8,9 The most common surgery used to remove pituitary tumors is called a transsphenoidal endoscopic surgery.1
Medical therapy is considered for patients who may not be good surgical candidates or for those with recurrent disease after tumor resection but patients are not suitable for repeat surgery. In some instances, medical therapy will be given before surgery.1
Radiotherapy (RT) is considered adjunctive treatment for patients not controlled by surgery and not responding to medical treatment or in patients who prefer RT.8,10
Medical therapies available:1,8
Somatostatin Analogs (SSAs)
Directly binds to somatostatin receptors in both the normal pituitary and pituitary adenoma cells to suppress GH secretion.
First-line treatment for acromegaly. Suppresses GH secretion in both normal pituitary and adenoma. SSAs also suppress IGF-1 secretion in the liver, thus controlling hormonal overproduction and tumor growth.
Dopamine Receptor Agonists
Works indirectly in acromegaly by stimulating dopamine receptors in the brain which inhibit GH secretion from the pituitary gland.
Often used as an adjunctive therapy (used in conjunction with somatostatin analogs). They are considered less effective than somatostatin analogs and considered for patients with mild biochemical abnormalities and mild symptoms.
GH-Receptor Antagonists
Lowers IGF-1 levels via competitive inhibition of endogenous GH binding to GH receptors.
Adjunctive therapy is unable to suppress GH secretion but lowers IGF-1 by competitive inhibition of endogenous GH binding to hepatocyte receptors. There is no anti-proliferative effects on the GH-secreting pituitary tumor; therefore, GH hypersecretion will persist and there is no affect to tumor size.
Adapted from: Daniel, CP et al.20
Somatostatin analog drugs
(1st and 2nd generation)8,9,11
- Have inhibitory actions on GH secretion
- Net effect will be to decrease levels of IGF-1 and GH over time and reduce tumor size
Somatostatin analogs (SSAs) – a closer look at first-line therapies12
Somatostatin (SST) is a hormone produced by various tissues in the body, including the hypothalamus, as a result of excess levels of GH. However, native SST in the body has a very short half-life — minutes due to the rapid degradation by peptidases in plasma and tissues, rendering it a poor candidate for therapeutic utility in its natural form.12 SSAs of natural SST have been synthetically developed to improve stability and retain pharmacological activity so that they can be used as an effective therapeutic modality.
To better understand the differences between SSA therapies available, it is important to recognize how SST elicits biological activity, specifically its impact on reducing levels of GH and IGF-1 in acromegaly patients. SST must bind to specific somatostatin receptors (SSTR) on the surface of somatotroph cells — 5 receptor subtypes have been identified (SSTR1 – SSTR5).12 Once SST binds to the SSTR, a signaling cascade is triggered and the inhibition of GH release is elicited.12
GH inhibition: biochemical control in patients with acromegaly13
Studies have shown that SSAs are effective in GH inhibition.13 However, newer analogs have a broader affinity to SSTRs, resulting in a higher effect on the inhibition of IGF-1 release.13 This may be in part to secondary changes in non-GH in the liver effecting IGF-1 secretion.13 In summary, somatostatin analogs have been demonstrated to achieve biochemical control.14
With the increased selectivity across multiple SSTRs with newer somatostatin analogs, there has been an observed increased incidence of hyperglycemia with this group of therapy.12 This adverse event is thought to be mechanism-based, given that insulin-producing beta cells express SSTR2 and SSTR5, and binding to these receptors results in the inhibition of insulin secretion.12 Data to date suggests hyperglycemia has been managed with oral diabetic medications.14
Explore a second-generation SSA with a unique binding profile.
Join our community of healthcare professionals interested in and dedicated to diagnosing and treating rare endocrine disorders.
REFERENCES: 1. Adigun OO, Nguyen M, Fox TJ, et al. Acromegaly. [Updated 2023 Feb 2]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan. Available from: https://www.ncbi.nlm.nih.gov/books/NBK431086/. 2. Giustina A, Biermasz N, Casanueva FF, et al. Acromegaly Consensus Group. Consensus on criteria for acromegaly diagnosis and remission. Pituitary. 2024 Feb;27(1):7-22. doi: 10.1007/s11102-023-01360-1. 3. Dekkers OM, Biermasz NR, Pereira AM, et al. Mortality in acromegaly: a meta-analysis. J Clin Endocrinol Metab. 2008;93: 61–67. doi: 10.1210/jc.2007-1191. 4. Ogedegbe OJ, Cheema AY, Khan MA, et al. A Comprehensive Review of Four Clinical Practice Guidelines of Acromegaly. Cureus. 2022;Sep 3;14(9):e28722. doi: 10.7759/cureus.28722. 5. Alhawyan FS. Mortality in Acromegalic Patients: Etiology, Trends, and Risk Factors. Cureus. 2021 Apr 2;13(4):e14265. doi: 10.7759/cureus.14265. 6. Biermasz NR, Dekker FW, Pereira AM, et al. Determinants of survival in treated acromegaly in a single center: predictive value of serial insulin-like growth factor I measurements. J Clin Endocrinol Metab. 2004;89: 2789–2796. doi: 10.1210/jc.2003-032041. 7. Bogazzi F, Colao A, Rossi G, et al. Comparison of the effects of primary somatostatin analogue therapy and pituitary adenomectomy on survival in patients with acromegaly: a retrospective cohort study. Eur J Endocrinol. 2013;169: 367–376. doi: 10.1530/EJE-13-0166. 8. Katznelson L, Atkinson JL, Cook DM, Ezzat SZ, Hamrahian AH, Miller KK; AACE Acromegaly Task Force. American Association of Clinical Endocrinologists Medical Guidelines for Clinical Practice for the Diagnosis and Treatment of Acromegaly–2011 update: executive summary. Endocr Pract. 2011 Jul-Aug;17(4):636-46. doi: 10.4158/ep.17.4.636. 9. Daniel CP, Wagner MJ, Borne GE, et al. Acromegaly: Pathophysiological Considerations and Treatment Options Including the Evolving Role of Oral Somatostatin Analogs. Pathophysiology. 2023 Sep 1;30(3):377-388. doi: 10.3390/pathophysiology30030029. 10. Cordido F, García Arnés JA, Marazuela Aspiroz M, Torres Vela E; grupo de Neuroendocrinología de la Sociedad Española de Endocrinología y Nutrición. Guía práctica de diagnóstico y tratamiento de la acromegalia [Practical guidelines for diagnosis and treatment of acromegaly. Grupo de Neuroendocrinología de la Sociedad Española de Endocrinología y Nutrición]. Endocrinol Nutr. 2013 Oct;60(8):457.e1-457.e15. Spanish. doi: 10.1016/j.endonu.2013.01.012. 11. Giustina A, Barkhoudarian G, Beckers A, et al. Multidisciplinary management of acromegaly: A consensus. Rev Endocr Metab Disord. 2020 Dec;21(4):667-678. doi: 10.1007/s11154-020-09588-z. 12. Gomes-Porras M, Cárdenas-Salas J, Álvarez-Escolá C. Somatostatin Analogs in Clinical Practice: a Review. Int J Mol Sci. 2020 Feb 29;21(5):1682. doi: 10.3390/ijms21051682. 13. Murray RD, Kim K, Ren SG, Chelly M, Umehara Y, Melmed S. Central and peripheral actions of somatostatin on the growth hormone-IGF-I axis. J Clin Invest. 2004 Aug;114(3):349-56. doi: 10.1172/JCI19933. 14. Colao A, Bronstein MD, Freda P, et al. Pasireotide C2305 Study Group. Pasireotide versus octreotide in acromegaly: a head-to-head superiority study. J Clin Endocrinol Metab. 2014 Mar;99(3):791-9. doi: 10.1210/jc.2013-2480. 15. SOMATULINE® DEPOT (lanreotide) injection, for subcutaneous use [prescribing information]. Cambridge, MA: Ipsen Biopharmaceuticals, Inc.; 2019. 16. SANDOSTATIN LAR® DEPOT (octreotide acetate) for injectable suspension, for gluteal intramuscular use [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corporation; 2021. 17. Poullot A-G, Chevalier N. New options in the treatment of Cushing’s disease: a focus on pasireotide. Res Rep Endocr Disord. 2013;3:31-38. doi: 10.2147/RRED.S30972.