Treatment of Aggressive Pituitary Adenomas: A Case-Based Narrative Review

Management of aggressive pituitary adenomas is challenging due to a paucity of rigorous evidence supporting available treatment approaches. Recent guidelines emphasize the need to maximize standard therapies as well as the use of temozolomide and radiation therapy to treat disease recurrence. However, often these adenomas continue to progress over time, necessitating the use of additional targeted therapies which also impact quality of life and long-term outcomes. In this review, we present 9 cases of aggressive pituitary adenomas to illustrate the importance of a multidisciplinary, individualized approach. The timing and rationale for surgery, radiation therapy, temozolomide, somatostatin receptor ligands, and EGFR, VEGF, and mTOR inhibitors in each case are discussed within the context of evidence-based guidelines and clarify strategies for implementing an individualized approach in the management of these difficult-to-treat-adenomas.

The future of somatostatin receptor ligands in acromegaly

Currently, first-generation somatostatin receptor ligands (fg-SRLs), octreotide LAR and lanreotide autogel, are the mainstays of acromegaly treatment and achieve biochemical control in approximately 40% of patients and tumor shrinkage in over 60% of patients. Pasireotide, a second-generation SRL, shows higher efficacy with respect to both biochemical control and tumor shrinkage but has a worse safety profile. In this review, we discuss the future perspectives of currently available SRLs, focusing on the use of biomarkers of response and precision medicine, new formulations of these SRLs and new drugs, which are under development. Precision medicine, which is based on biomarkers of response to treatment, will help guide the decision-making process by allowing physicians to choose the appropriate drug for each patient and improving response rates. New formulations of available SRLs, such as oral, subcutaneous depot and nasal octreotide, may improve patients’ adherence to treatment and quality of life since there will be more options available that better suit each patient. Finally, new drugs, such as paltusotine, somatropin, ONO-5788 and ONO-ST-468, may improve treatment adherence and present higher efficacy than currently available drugs.

gsp Mutation Is Not a Molecular Biomarker of Long-Term Response to First-Generation Somatostatin Receptor Ligands in Acromegaly

Background: It is still controversial if activating mutations in the stimulatory G-protein α subunit (gsp mutation) are a biomarker of response to first generation somatostatin receptor ligands (fg-SRL) treatment in acromegaly. Thus, we aimed to evaluate whether gsp mutation predicts long-term response to fg-SRL treatment and to characterize the phenotype of patients harboring gsp mutations. Methods: GNAS1 sequencing was performed by Sanger. SST2 and SST5 were analyzed by immunohistochemistry (IHC) and real-time RT-PCR. The cytokeratin granulation pattern was evaluated by IHC. Biochemical control was defined as GH < 1.0 ng/mL and normal age-adjusted IGF-I levels. Results: gsp mutation was found in 54 out of 136 patients evaluated. Biochemical control with fg-SRL treatment was similar in gsp+ and gsp- patients (37% vs. 25%, p = 0.219). Tumors harboring gsp mutation were smaller (p = 0.035) and had a lower chance of invading cavernous sinuses (p = 0.001). SST5 protein (p = 0.047) and mRNA (p = 0.013) expression levels were higher in wild-type tumors. Conclusions: In this largest series available in the literature, we concluded that gsp is not a molecular biomarker of response to fg-SRL treatment in acromegaly. However, the importance of its negative association with cavernous sinus invasion and SST5 expression needs to be further investigated.

The Association Between Somatostatin Receptor Ligand and Vitamin B12 Levels in Patients With Acromegaly

Purpose: Vitamin B12 causes hematologic and neuropsychiatric disorders, so it is important to evaluate it in risky situations. In this study, we aimed to evaluate the association between somatostatin receptor ligands and vitamin B12 levels in patients with acromegaly.Methods: Patients who were followed up with the diagnosis of acromegaly in the Endocrinology and Metabolism outpatient clinic of Istanbul University-Cerrahpaşa Medical Faculty were evaluated. Patients were divided into groups according to their somatostatin receptor ligand use status. The groups were evaluated according to their vitamin B12 levels, demographic data, and biochemical parameters.Results: One hundred fifty-two patients were evaluated. Thirteen patients had vitamin B12 deficiency. The majority (11/13) of patients with vitamin B12 deficiency were patients using somatostatin receptor ligand. In addition, the number of patients with vitamin B12 deficiency who received lanreotide autogel treatment was significantly higher compared with patients who did not use somatostatin receptor ligand (p = 0.011). Vitamin B12 levels were higher in patients who received lanreotide autogel treatment than in patients who did not use somatostatin receptor ligand treatment (p = 0.040). There was a negative correlation between vitamin B12 levels and lanreotide autogel use time, cumulative lanreotide autogel dose.Conclusion: It is important to evaluate the level of vitamin B 12 in the follow-up of patients with acromegaly using somatostatin receptor ligand treatment.