Cushing's Info

(Ivanhoe Newswire) – Cushing’s disease is a rare disorder of chronic hypercortisolism due to a corticotropin-secreting pituitary adenoma. Despite high remission, surgery has been the best option to treat it. Now doctors are shedding light on a new way to target the disease.

Cushing’s disease is associated with central obesity, osteoporosis, arterial hypertension, insulin resistance, glucose intolerance, diabetes mellitus, dyslipidemia, cardiovascular disease, and increased mortality. The next line of defense after surgery is to try radiation therapy, bilateral adrenalectomy, and medical therapy, but doctors are now looking at something new.

162 adults, with a confirmed persistent or recurrent Cushing’s disease or newly diagnosed disease, were randomly selected to participate in a double-blind, phase 3 study. These patients were given a subcutaneous pasirotide (SOM230) – a somatostatin analogue that targets four of the five somatostatin receptors, with highest affinity for subtype— at a dose of 600 µg (82 patients) or 900 µg (80 patients) twice daily.

Patients with urinary free cortisol not exceeding two times the upper limit of the normal range and not exceeding the baseline level in the third months continued to receive their randomly assigned dose; all others received an additional 300 µg two times daily. The primary end point was a urinary free cortisol level at or below the upper limit of the normal range at month 6 without an increased dose. Open-label treatment continued through well into the twelfth month.

Results showed that twelve of the 82 patients in the 600-µg group and 21 of the 80 patients in the 900-µg group met the primary end point. The median urinary free cortisol level decreased by approximately 50% by the second month and remained stable in both groups. A normal urinary free cortisol level was achieved more frequently in patients with baseline levels not exceeding five times the upper limit of the normal range than in patients with higher baseline levels. Serum and salivary cortisol and plasma corticotropin levels decreased, and clinical signs and symptoms of Cushing's disease diminished.

Pasireotide was associated with hyperglycemia-related adverse events in 118 of 162 patients; other adverse events were similar to those associated with other somatostatin analogues. Despite declines in cortisol levels, blood glucose and glycated hemoglobin levels increased soon after treatment initiation and then stabilized; treatment with a glucose-lowering medication was initiated in 74 of 162 patients.

Researchers concluded that the significant decrease in cortisol levels in patients with Cushing's disease who received pasireotide supports its potential use as a targeted treatment for corticotropin-secreting pituitary adenomas.

SOURCE: New England Journal of Medicine, March 2012.

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