Cushing’s disease, the result of corticotroph pituitary adenoma hypersecretion of ACTH and hypercortisolemia, is associated with significant morbidities and increased mortality.1 When curative resection is not possible or successful, medical management is required.
However, currently the medical management of Cushing’s disease is difficult because:
* There are no approved medications for the treatment of Cushing’s disease2
* Inhibitors of steroidogenesis are poorly efficacious and have significant side effects1
* Current somatostatin analogs that bind primarily to SST2 are not effective in this disease2,3
Corticotroph Adenomas: Key Somatostatin Receptor Subtypes and Functions
Human corticotroph adenomas express all of the somatostatin receptor subtypes, but:
* SST5 is mainly expressed4,5
* Other receptors show lesser expression4,5
* In vitro data suggests SST5 predominates in regulating ACTH release5,6
* SST2 has a less significant role in regulating ACTH release5,6
* Other data suggest that activation of SST2 and SST3 induce apoptosis and inhibit proliferation which may have therapeutic significance7
Classic Features of Cushing’s Disease
Pasireotide in Cushing’s Disease: Cortisol Control
Pasireotide in Cushing’s Disease: A Phase II Study
Pasireotide, which binds with high affinity to 4 of the 5 somatostatin receptor subtypes8, has been studied in patients with de novo, persistent, or recurrent Cushing’s disease.2
In a phase II study of 15-day duration:2
* 76% of the patients demonstrated reductions in urinary free cortisol (UFC reducers)
* 17% achieved normal levels (UFC responders)
* Serum cortisol and plasma ACTH levels were also reduced
Adapted from Boscaro M, et al.2
PASPORT Cushing’s
PASPORT Cushing’s, part of the PASPORT clinical trial research program, will further evaluate the safety and efficacy of pasireotide in patients with Cushing’s disease. This study is designed as a registration trial for pasireotide in Cushing’s disease.
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