Approach to the patient: Precision Medicine-Guided Evaluation and Treatment of Acromegaly.

Abstract

Acromegaly is a heterogeneous disease in which delayed biochemical control remains common despite the availability of multiple therapeutic options. Traditional stepwise medical treatment algorithms often rely on the use of first-generation somatostatin ligands (fgSRLs) as the first line drugs with the empirical escalation and trial-and-error approaches, prolonging patients' exposure hormonal excess.Cluster analyses indicate that overall, three main classes of patients with acromegaly representing distinct biological phenotypes can be recognized: (1) young patients with invasive macroadenomas and frequent resistance fgSRLs; (2) older patients with noninvasive tumors and SRL responsiveness in the majority of them; and (3) patients with intermediate features often requiring combination medical therapy in whom prediction of response is more challenging.From a practical perspective, biomarker-guided treatment selection based on T2-weighted MRI signal intensity, the short acute octreotide test, and tumor immunohistochemistry, following the strategy validated in the ACROFAST study, is applicable in clinical practice. It allows a prompt biochemical control and tumor volume reduction, a rationale leading to superior effectiveness performance than the classic sequencing therapy involving the universal utilization of fgSRLs as first option.In the era of integrative and participative medicine, such a protocol enables the early identification of most patients unlikely to respond to fgSRLs, thus supporting timely initiation of pegvisomant, pasireotide or combination therapy, and to achieve hormonal control in nearly 80% of patients. Precision medicine has become a practical reality in acromegaly. A biomarker-guided strategy improves therapeutic efficiency and should be incorporated into contemporary clinical practice.