Pasireotide-Induced Shrinkage in GH and ACTH Secreting Pituitary Adenoma: A Systematic Review and Meta-Analysis

Abstract

IntroductionPasireotide (PAS) is a novel somatostatin receptor ligands (SRL), used in controlling hormonal hypersecretion in both acromegaly and Cushing’s Disease (CD). In previous studies and meta-analysis, first-generation SRLs were reported to be able to induce significant tumor shrinkage only in somatotroph adenomas. This systematic review and meta-analysis aim to summarize the effect of PAS on the shrinkage of the pituitary adenomas in patients with acromegaly or CD.Materials and methodsWe searched the Medline database for original studies in patients with acromegaly or CD receiving PAS as monotherapy, that assessed the proportion of significant tumor shrinkage in their series. After data extraction and analysis, a random-effect model was used to estimate pooled effects. Quality assessment was performed with a modified Joanna Briggs’s Institute tool and the risk of publication bias was addressed through Egger’s regression and the three-parameter selection model.ResultsThe electronic search identified 179 and 122 articles respectively for acromegaly and CD. After study selection, six studies considering patients with acromegaly and three with CD fulfilled the eligibility criteria. Overall, 37.7% (95%CI: [18.7%; 61.5%]) of acromegalic patients and 41.2% (95%CI: [22.9%; 62.3%]) of CD patients achieved significant tumor shrinkage. We identified high heterogeneity, especially in acromegaly (I2 of 90% for acromegaly and 47% for CD), according to the low number of studies included.DiscussionPAS treatment is effective in reducing tumor size, especially in acromegalic patients. This result strengthens the role of PAS treatment in pituitary adenomas, particularly in those with an invasive behavior, with progressive growth and/or extrasellar extension, with a low likelihood of surgical gross-total removal, or with large postoperative residual tissue.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022328152, identifier CRD42022328152

Approach of Acromegaly during Pregnancy

“…One the other hand, active disease under first-generation SSAs represents an indicator of a more severe form, most patients becoming candidates for either pasireotide or pegvisomant in terms of pharmacological intervention [ 20 , 66 , 67 ]. Other comorbidities with a major impact on overall health are represented by cardio-metabolic complications, particularly HBP and DM, which are partially controlled by standard intervention for acromegaly [ 68 , 69 , 70 ].…”

Magnetic resonance imaging as a predictor of therapeutic response to pasireotide in acromegaly

“…These results are in line with those previously published. 27 Another relevant aspect of the imaging analysis of the tumour in patients with acromegaly treated with pasireotide is the dynamic changes observed over time, as described by Coopmans et al 21 In this later study, sequential imaging while on pasireotide treatment showed that a number of cases presented an increment in the hyperintense signal and this increase correlated with the magnitude of shrinkage effect as well as the hormonal control. The interpretation was that a cytolytic effect would apply in those patients, leading to a tumour mass reduction and in parallel to an amelioration of hormonal hypersecretion, probably also related to a decrease in viable somatotroph cellular mass.…”

Impairment in insulin secretion without changes in insulin resistance explains hyperglycemia in patients with acromegaly treated with pasireotide LAR

“…IGF-1 concentrations significantly decreased during the study and normalized in 58% of the included patients. Furthermore, the positive effects on tumor size ( 12 , 39 ) could be confirmed, as an increase of more than 20% in tumor size was observed only in a single patient.…”