Acromegaly Management: Focus on Biochemical Control at ENDO 2026

Acromegaly results from a somatotroph adenoma in the pituitary gland, leading to chronic overproduction of GH and consequently, insulin-like growth factor-1 (IGF-1).¹ The long-term sequelae include cardiovascular disease, diabetes mellitus, arthropathy, and an increased risk of certain malignancies.³ The primary goals of treatment are tumour mass reduction, normalisation of GH and IGF-1 levels, and alleviation of symptoms, thereby improving quality of life and reducing mortality.⁴ Surgical resection of the pituitary adenoma is typically the first-line treatment for most patients. However, complete biochemical remission post-surgery is achieved in approximately 40% to 80% of cases, depending on tumour size and invasiveness.⁵ For patients with persistent disease or those unsuitable for surgery, medical therapy forms the cornerstone of management.

Current Therapeutic Landscape and Unmet Needs

Somatostatin receptor ligands (SRLs), such as octreotide and lanreotide, are the most commonly used medical therapies, targeting somatostatin receptors (SSTR2 and SSTR5) on the adenoma to inhibit GH secretion.⁶ These agents achieve biochemical control (normalisation of IGF-1 and suppressed GH) in approximately 50% to 70% of patients.⁷ Dopamine agonists (e.g., cabergoline) are less potent but can be effective, particularly in patients with mild IGF-1 elevation or co-secretion of prolactin, achieving control in about 30% to 40% of selected patients.⁸ Pegvisomant, a GH receptor antagonist, blocks the action of GH at target tissues, normalising IGF-1 levels in 70% to 90% of patients, but does not reduce tumour size or GH levels.⁹

Despite these available options, a significant clinical challenge persists: a substantial number of patients do not achieve biochemical control with monotherapy. Data presented at ENDO 2026 highlighted that real-world remission rates, particularly with SRL monotherapy, can be lower than those reported in clinical trials, sometimes falling below 50%.² This discrepancy underscores the need for more effective treatment strategies and a personalised approach to patient management. The long-term consequences of uncontrolled disease, even with mild elevations in IGF-1, necessitate a proactive approach to therapy escalation.

Combination medical therapy is increasingly recognised as a strategy for patients who do not achieve control with monotherapy. Combining SRLs with pegvisomant has demonstrated superior efficacy in normalising IGF-1 compared to SRL monotherapy, with IGF-1 normalisation rates reaching 70% to 90%.¹⁰ Similarly, the combination of SRLs with cabergoline can be effective in some patients, particularly those with higher SSTR5 expression or co-secreting tumours.¹¹ Radiation therapy, including conventional external beam radiation and stereotactic radiosurgery, is another option for patients with persistent disease after surgery and medical therapy, though its effects are delayed and it carries risks of hypopituitarism and secondary tumour formation.¹²

Limitations in current management include the need for frequent injections for SRLs and pegvisomant, which can impact patient adherence and quality of life. Furthermore, predicting response to specific therapies remains challenging, as individual tumour characteristics and receptor expression profiles vary. The cost of long-term medical therapy also represents a significant burden on healthcare systems. Future research is focused on developing novel agents, such as new SSTR subtypespecific agonists and oral formulations, as well as refining biomarkers to guide treatment selection. The ongoing challenge is to identify patients who will benefit most from specific therapies or combinations, moving beyond a trial-and-error approach to a more precision-based medicine model for acromegaly.