Discussion
pituitary tumor, tumor, mild/moderate, hypercortisolemia, hypercortisolism
PITUITARY TUMOR, TUMOR, DISEASE, HYPERCORTISOLEMIA, HYPERCORTISOLISM
The severe morbidity and increased mortality with uncontrolled CD highlight the importance of identifying an effective medical strategy. This study explored the potential of a synergistic benefit of the addition of cabergoline to pasireotide treatment in patients with CD.Complete normalization of cortisol production is required to reverse the risks of morbidity and mortality in patients with CD (This study confirms previous reports that patients with mild hypercortisolism at baseline were more likely to achieve mUFC control with pasireotide monotherapy than patients with moderate or severe hypercortisolism (Improvements in clinical signs and symptoms with pasireotide monotherapy were consistent with published data (The overall safety profile was consistent with that expected for pasireotide, with most AEs being mild/moderate (Both pasireotide and cabergoline are pituitary-targeted agents that act directly on the source of the disease via inhibition of ACTH release by the corticotroph tumor, which may be an advantage over steroid synthesis inhibitors. This study further confirms previous data reporting the benefits of pasireotide in combination with cabergoline in patients with CD (Although clinicians have several therapeutic options at their disposal to treat hypercortisolemia associated with CD, the optimal treatment approach should be based on the individual clinical situation and the benefit–risk considerations for each patient. In this study, 13 patients had history of pituitary radiation, with a duration of at least 2.6 years (median 3.3 years) between the last radiation treatment and the observed response date. However, only 7/13 patients achieved the therapeutic target. Although there was a gap of > 2 years, we cannot exclude the role of radiation in normalizing UFC. Contrastingly, 6/13 patients treated with radiation did not achieve mUFC ≤ULN (responders) at Week 35. The impact of the adjuvant radiation therapy remains unclear.The strengths of this study are that this is the largest and longest prospective study with pituitary-directed pharmacotherapy, to date, evaluating the addition of cabergoline to pasireotide in patients with CD, and this stepwise approach reflects real-world clinical practice (Other limitations include protocol deviations in including 3 patients with normal UFC at baseline (one patient was uncontrolled at rescreen, and one was discontinued at 2 weeks - both classified asnon-responders), lack of data on impact of radiation therapy without study drug in patients who gained biochemical control with adjuvant radiation therapy, lack of pituitary magnetic resonance imaging to detect pituitary tumor changes, lack of data about effective cabergoline dose and absence of cardiac valve assessment for mild to moderate severity in the medium term. Both pasireotide and cabergoline can induce tumor shrinkage in CD (