Acromegaly is a rare and severe disease caused by an increased and autonomous secretion of
growth hormone (GH), thus resulting in high circulating levels of
insulin-like growth factor 1 (IGF-1). Comorbidities and mortality rate are closely related to the disease duration. However, in most cases achieving biochemical control means reducing or even normalizing mortality and restoring normal life expectancy. Current treatment for
acromegaly includes neurosurgery,
radiotherapy and medical
therapy. Transsphenoidal surgery often represents the recommended first-line treatment. First-generation
somatostatin receptor ligands (SRLs) are the
drug of choice in patients with persistent disease after surgery and are suggested as first-line treatment for those ineligible for surgery. However, only about half of patients treated with
octreotide (or
lanreotide) achieve biochemical control. Other available drugs approved for clinical use are the second-generation SRL
pasireotide, the
dopamine agonist cabergoline, and the GH-receptor antagonist
pegvisomant. In the present paper, we revised the current literature about the management of
acromegaly, aiming to highlight the most relevant and recent therapeutic strategies proposed for patients resistant to first-line medical
therapy. Furthermore, we discussed the potential molecular mechanisms involved in the variable response to first-generation SRLs. Due to the availability of different medical
therapies, the choice for the most appropriate
drug can be currently based also on the peculiar clinical characteristics of each patient.