Introduction: A significant number of GH-secreting pituitary adenomas show an aggressive behavior, therefore, when uncontrolled acromegaly persists, a pharmaceutical combination may improve biochemical control, with reduction of disease morbidity and mortality. We aimed to describe the clinical features of four patients successfully treated with a pharmacological combination of pasireotide LAR, pegvisomant and cabergoline.
Case reports: Acromegaly was diagnosed in young age, except for one patient that received diagnosis at the age of 65. Hormonal assays documented impaired secretion of IGF-1 (>1100 ng/ml) and GH (>8 ng/ml), without any suppression at OGTT. Contrasted pituitary and brain MR showed in all cases the presence of a pituitary macroadenoma extending in the cavernous sinuses, optical chiasm, sphenoid sinus and third ventricle. Patients underwent one or two neurosurgical procedures through the transfenoidal approach and, in one case, through the transcranial route. In one patient, neurosurgery was not carried out because of multiple comorbidities. Histological examination demonstrated pituitary adenomas with diffuse immunostaining for GH and, in one case, also for PRL, with Ki67 labelling index >1.5%. Immunohistochemistry for SSTRs subtypes showed in one case high expression of SSTR5 (score 3) and absence of SSTR2 (score 0) and in another case decreased expression of both SSTR 2 and SSTR5 (score 2). According to persistence of high levels of IGF-1 after neurosurgery and after SSAs and DA combined treatment (>1000 ng/ml), pegvisomant was added in increasing dosage up to 30 mg/day, without any important biochemical improvement (IGF-1 >500 ng/ml). Thus, patients suspended conventional SSAs therapy and began pasireotide Lar up to 60 mg/month, with improved disease control (IGF-1 age- and sexed-normalized) and stability of residual tumor mass at radiological evaluation. None of patients had significant adverse effects, particularly worsening of glycemic status.
Conclusions: Treating patients with acromegaly can be extremely challenging, and inadequate disease control may lead to serious consequences. Pegvisomant and combination therapies have been used to manage patients uncontrolled on first-generation SSAs. Several factors can predict poor response to SSAs, such as young age, high tumor size, elevated Ki67 index, reduced SSTR2/SSTR5 and sparsely granulated pattern of tumor. Pasireotide LAR seems to be a promising medical therapy for patients that cannot be controlled with conventional SSAs, accordingly to the pattern of SSTRs expression. Therefore, a multimodal therapeutic approach with pasireotide LAR, cabergoline and pegvisomant can be effective and safe in the management of resistant disease.
19 May 2018 - 22 May 2018