Endocrine Abstracts

Introduction: Pasireotide is a potent somatostatin analogue (SSA) and used in therapy-refractory acromegaly, commonly after failure of treatment with first-generation SSA. However, it may induce severe hyperglycemia, which usually occurs rapidly after initiation of therapy and in general gradually improves over time. We here present two cases of young male patients who developed severe pasireotide-induced hyperglycemia after several years of treatment.

Case 1: The patient was diagnosed with gigantism due to a growth hormone secreting pituitary macroadenoma at the age of 17 and received pituitary surgery one month after diagnosis. Due to residual tumor tissue the patient received medical treatment with a dopamine agonist and then octreotide. However, only partial biochemical control has been achieved. Additional Gamma-Knife radiosurgery 3 years after diagnosis did not result in biochemical control within the following years. Ultimately, the patient was started on pasireotide subcutaneously in a clinical trial 8 years after diagnosis and reached biochemical control within months. After two years therapy was switched to pasireotide LAR. Glycemic status remained stable during the first 3 years of pasireotide therapy, but then HbA1c and fasting plasma-glucose (FPG) levels quickly increased and we initiated antidiabetic treatment. Pasireotide was continued. Currently, he is on a combination therapy with metformin, sitagliptin, and repaglinide with acceptable glycemic status while maintaining biochemical remission.

Case 2: The diagnosis of acromegaly was established in a 27-year-old male presenting with acral enlargement, paresthesia of both hands, thickening of fingers, prognathism, and progressive asthenia. Transsphenoidal resection of a pituitary macroadenoma ensued quickly, but IGF-I levels remained equally elevated during the months following surgery. He was treated with lanreotide, almost achieving biochemical control but with persistent clinical signs of active disease. The patient was then started on pasireotide subcutaneously in a clinical trial achieving IGF-I levels below the upper limit of normal. After two years the treatment was switched to pasireotide LAR. Afterwards FPG steadily increased and after two further years antidiabetic treatment became necessary. After two more years FPG and HbA1c continued to rise. As the patient refused more intensive antidiabetic treatment pasireotide had to be stopped. Glycemic status returned to normal thereafter.

Conclusion: We present two cases of patients with acromegaly who developed severe hyperglycemia only after several years of pasireotide treatment. Therefore, long-term monitoring of glucose control is necessary in the follow-up of pasireotide treatment.