<p>Octreotide-Resistant Acromegaly: Challenges and Solutions</p>

Abstract

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.

Real-world experience with pasireotide-LAR in resistant acromegaly: a single center 1-year observation

“…It should be noted that younger patients, especially males (who constituted the majority of studied group), are more often resistant to treatment with SRLs [ 22 ]. A similar relationship was demonstrated for patients with higher GH and IGF-1 levels at diagnosis [ 23 ]. Patients with FIPA, McCune-Albright syndrome and acrogigantism accounted for a large portion of the studied population.…”

Clinical and Radiological Predictors of Biochemical Response to First-Line Treatment With Somatostatin Receptor Ligands in Acromegaly: A Real-Life Perspective

“…All these aspects are associated with the long-term exposure to inappropriately high circulating levels of GH and IGF-1 (6). Late diagnosis is an important issue in acromegaly, since it can be delayed up to 10 years after the onset of early symptoms (1,7,8). Nowadays, surgical resection of the pituitary tumor performed by a skilled neurosurgeon is the first treatment choice in most patients (9,10).…”

Octreotide and Pasireotide Combination Treatment in Somatotroph Tumor Cells: Predominant Role of SST2 in Mediating Ligand Effects

“…First-generation somatostatin receptor ligands (fg-SRLs), octreotide (OCT) and lanreotide (LAN), still represent the first choice as medical treatment in acromegaly patients [ 2 , 5 , 6 ]. Both OCT and LAN are stable octapeptides showing a preferential binding affinity for the somatostatin receptor subtype 2 (SST 2 ), widely expressed in GH-secreting pituitary tumor cells [ 7 , 8 ].…”