Endocrine Abstracts

Background: A recent, large phase III study (n=162) showed that treatment with pasireotide rapidly decreased urinary free cortisol (UFC) levels and improved signs and symptoms in patients with Cushing’s disease. Here, we report the experience of a patient enrolled in this trial who received pasireotide for 36 months.

Results: A 31-year-old male presented in June 2008 with persistent Cushing’s disease despite two previous pituitary surgical procedures. Examination revealed he was overweight (79 kg; BMI 28.3 kg/m²), had mild hypertension (139/83 mmHg), and elevated UFC (112.5 μg/24 h; ULN, 52.6) and ACTH (55 ng/l; ULN, 46); his serum cortisol level was 10.5 μg/dl (ULN, 22.4). In July 2008, he began twice-daily injections of pasireotide 600 μg s.c. After 3 months, UFC had decreased to 72.0 μg/24 h. In January 2009 (UFC 73.8 μg/24 h), the pasireotide dose was increased to 900 μg s.c. bid. By July 2009 (end of 12-month core study), an improvement in all key biochemical parameters was observed: UFC (36.4 μg/24 h) and ACTH (31 ng/l) normalized, and serum cortisol decreased (7.8 μg/dl). Reductions in weight (69 kg), BMI (24.7 kg/m²) and blood pressure (127/70 mmHg) were also reported. Pasireotide 900 μg bid was continued and at 18 months, although UFC was slightly elevated (58.0 μg/24 h), clinical improvements were maintained, including blood pressure (116/80 mmHg), weight (72 kg) and BMI (25.8 kg/m²). After 36 months’ treatment with pasireotide, UFC was normalized (33.7 μg/24 h), and improvements from baseline in weight (74 kg), BMI (26.2 kg/m²) and blood pressure (125/82 mmHg) were sustained. The patient’s health-related quality of life also improved, as evaluated by the CushingQoL questionnaire. Several adverse events occurred that were suspected to be related to the study drug: mild (grade 1) hyperglycemia was noted at 6 and 9 months, while at 18 months, moderate (grade 2) hyperglycemia occurred, necessitating initiation of metformin, then glimepiride due to gastrointestinal complaints. Mild hyperglycemia was reported again at 27 months. Grade 2 cholelithiasis was also reported at month 12.

Conclusions: This case report illustrates the long-term efficacy and safety of pasireotide in Cushing’s disease, supporting its potential use as a targeted treatment for ACTH-secreting pituitary adenomas.

Declaration of interest: I fully declare a conflict of interest. Details below:

Funding: This work was supported, however funding details unavailable.