Endocrine Abstracts

The management of Cushing’s disease (CD) can be problematic, particularly when the disease persists following pituitary surgery. Here we report the case of a 55-year old woman with CD that persisted after repeat transsphenoidal surgery. The patient had an overt phenotype with facial rubeosis, central obesity with supraclavicular fat accumulation, cervical fat pad and proximal muscle weakness. She had received anti-hypertensive drugs and insulin for diabetes mellitus. Hormonal evaluations confirmed active hypercortisolism with absent cortisol rhythm, elevated midnight plasma cortisol (15.9 μg/dl) and increased 24-h urinary free cortisol (UFC>5×ULN) levels. After fulfilling inclusion criteria, the patient was randomized to pasireotide 900 μg b.i.d. in the Phase III study CSOM230B2305. During the first 3 months of treatment, UFC levels decreased from baseline by almost 50%. This was associated with improved clinical appearance (reduced facial rubeosis and supraclavicular fat accumulation; weight decrease of 7%), although worsening of diabetes was also observed. However, UFC levels remained elevated (2.5×ULN) and the patient was considered to be a non-responder, therefore pasireotide dose was up-titrated to 1200 μg bid. From month 6 the patient had a progressive clinical and biochemical improvement, with resolution of hypertension, improvement of diabetes mellitus (with discontinuation of insulin and introduction of an oral hypoglycemic), and remission of all typical features of CD. Overall, her weight decreased by ~30% from baseline. The patients’ quality-of-life significantly improved, as did her sense of well being. At month 12, UFC levels were normalized and cortisol rhythm restored. Pasireotide dose was progressively reduced to 300 μg b.i.d. After 3 years the patient is still receiving pasireotide 300 μg b.i.d. with no loss of efficacy. In conclusion, short-term results are not always predictive of long-term response. In addition, pre-existing diabetes is not a contraindication to pasireotide treatment because the control of CD may outweigh any negative effects on glucose metabolism.