ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2019) 63 GP163 | DOI: 10.1530/endoabs.63.GP163

Effects of a single dose of pasireotide on glucose metabolism in patients with Cushing's disease and predictors of diabetes mellitus developement during treatment

Mattia Barbot, Daniela Regazzo, Marialuisa Zilio, Alessandro Mondin, Laura Lizzul, Silvia Pinelli & Carla Scaroni

Endocrinology Unit, Department of Medicine-DIMED, University of Padova, Padova, Italy.

Introduction: Pasireotide (PAS) is an effective treatment for Cushing’s disease (CD) but its use is burdened by the high incidence of diabetes mellitus (DM). We aimed to evaluate the effect of a single subcutaneous injection of PAS on glucose metabolism in CD patients, to identify factors predicting rapid deterioration of glycaemic control.

Methods: 14 patients [(f/m=12/2, mean age 43±11.3 years, follow-up 17 months (2-63)] with CD treated with PAS (600 μg b.i.d.) were studied; before treatment initiation, all patients were submitted to an acute PAS test (600 mcg s.c.) with measurements of ACTH, cortisol, glucose, insulin, c-peptide, insulin, GIP, glucagon, GLP-1, ACTH and cortisol at time 0’ and then every 30’ minutes for 2 hours to predict the development of DM.

Results: There was a significant reduction in urinary free cortisol (UFC, 582±456 vs 254±356 nmol/24h, P=0.001) and late night salivary cortisol (LNSC, 12.2±11.6 vs 3.8±1.7 nmol/L, P=0.003) in all cohort with concomitant improvement of weight (P=0.01) and waist circumference (P=0.02). Overall 10/14 patients reached UFC normalization whereas LNSC was within normal range only in 4 cases. A single PAS dose produced a significant decrease of all hormonal parameters assessed (P<0.0001), except for glycaemia which reached the highest value 120’ after the injection (baseline 4.65±0.52 vs peak 8.91±3.63 mmol/L, P<0.0001). Overall 7/14 patients developed DM within the first 2 months of therapy. Among baseline characteristics, non-DM patients did not differ in age, weight, visceral adiposity, HOMA-index, fasting glucose and severity of CD from those who did not have glucose metabolism alterations; however, compared to non-DM patients, DM patients displayed higher baseline fasting c-peptide (respectively 694.4±109.6 vs 947.4±318.4 pmol/L, P=0.05) and HbA1c levels (30±3.0 vs 37.1±1.8 mmol/mol, P=0.001), with the latter being normal in all cases. Finally, glucose peak tent to be higher in DM-patients than in those who did not develop hyperglycaemia (7.2±2.2 vs 10.6±4.1mmol/L, P=0.06).

Conclusions: PAS confirmed to be a valuable tool for the treatment of CD. It was able to rapidly suppress insulin secretion and the incretin system with a subsequent increase in glucose levels into the diabetic range producing also a concomitant decrease in glucagon values. Patients at higher risk of DM during PAS therapy were those with higher fasting c-peptide at elevated serum glucose peak during the acute test. Interestingly baseline HbA1c, seems to predict the risk of PAS-induced DM.

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