Abstract
Cushing’s disease is a rare condition of chronic hypercortisolism caused by an adrenocorticotropic
hormone-secreting pituitary adenoma and associated with debilitating complications
and excess mortality. Transsphenoidal adenomectomy is generally first-line treatment
but is contraindicated in some patients and associated with significant post-surgical
recurrence. While there are few data to support long-term use of most pharmacologic
treatments, pasireotide (a multireceptor-targeted somatostatin analog) recently demonstrated
sustained benefit in a 12-month, multicenter, Phase III trial and in 2 long-term extension
studies. The Phase III trial (N=162) demonstrated reductions in urinary free cortisol
in most patients, with durable treatment effect over 12 months. Biochemical improvement
was generally paralleled by reductions in Cushing’s-related signs and symptoms and
enhanced health-related quality of life. Long-term treatment was evaluated in 58 patients
who entered a planned 12-month extension phase. Reductions in urinary free cortisol
remained stable throughout the extension, with further improvements noted in clinical
signs and symptoms. Similar results were reported in the smaller Phase II extension
(N=18; median treatment duration, 9.7 months; range, 2 months–4.8 years). Case reports
have recently emerged demonstrating sustained disease control for upto 7 years in
some patients. Safety considerations for long-term medical treatment with pasireotide
are generally similar to those for other somatostatin analogs, except for the incidence
and severity of hyperglycemia. Most patients experience new or worsening hyperglycemia
with pasireotide treatment. Expert recommendations for treatment of pasireotide-associated
hyperglycemia have recently been published and new studies are planned to elucidate
the optimal treatment approach for pasireotide-associated hyperglycemia.
Key words cushing - cushing’s syndrome - somatostatin analog - corticotroph adenoma
