Glucose Control in Patients with Acromegaly Resistant to FirstLine Somatostatin Receptor Analogues Monotherapy

Growth hormone (GH) receptor antagonist (Pegvisomant) has been shown to obtain IGF1 normalization in 60-90% of patients with acromegaly and amelioration of glucose metabolism in clinical trials. The aim of the study is to evaluate the effect of GH receptor antagonist in monotherapy versus combined therapy with somatostatin receptor analogues (SSRA) with or without dopamine agonist (DA) therapy on glucose metabolism related to acromegaly control. Patients and Methods 37 patients with GH secreting pituitary adenoma previously operated and not cured, totally or partially resistant to SSRA therapy, treated with pegvisomant as monotherapy or combined with SSRA with or without DA therapy, consecutively evaluated in Neuroendocrinology Clinic from Institute of Endocrinology between January2001-March2019. Baseline and at 6 months, at 1, 2, 3- and 5-years serum IGF1, glucose, HbA1c, and pituitary tumour diameters were recorded. Results IGF1 levels were lowered after 6 months and 1year of treatment and then remained stable at 2,3 and 5 years of treatment with Pegvisomant (from 2.3 +/- 0.2 xULN to 1.94 +/- 0.18 and 1.43 +/- 0.16 xULN at baseline, 6 months and 1 year, respectively, p=0.06 baseline versus 6 months and 0.001 baseline versus 1 year). We obtained control of acromegaly in 20% of patients at 6 months, and in 38% and 54.5 % after 1 and 3 years of treatment. 11 patients had diabetes mellitus (29.72%) and 2 (5.4%) patients had dyskinesia at baseline. After the first 6 months of therapy glucose level significantly decreased only in patients treated with Pegvisomant monotherapy (p=0.02) and not in patients with combined therapy (p=0.4), while glycated haemoglobin did not change significantly. Conclusion In patients with acromegaly resistant to somatostatin receptor analogues monotherapy, GH receptor antagonist therapy is efficient in controlling IGF1 levels. Glucose levels improved after the first 6 months of Pegvisomant monotherapy, but not in patients with combined therapy.