Isturisa can safely manage cyclic Cushing’s disease: Case report
Medication eased symptoms within 3 weeks for 68-year-old US man
Cyclic Cushing’s disease — where bouts of high cortisol levels come and go — can be safely and effectively managed with Isturisa (osilodrostat) when surgery isn’t an option, according to a new case report from researchers in California.
The report detailed the case of a man in his late 60s who had experienced repeat bouts of Cushing’s symptoms. However, doctors could not identify a source well enough to perform surgery, the preferred first-line treatment for the rare condition.
The clinicians instead started the man on Isturisa, an oral medication approved in the U.S. for certain patients with high levels of cortisol in the blood, which led to improvements within three weeks.
“We present the first case to our knowledge demonstrating successful treatment of cyclic Cushing’s … with [Isturisa],” the researchers wrote, noting that the therapy “showed rapid and safe control of hypercortisolism.”
The case report, titled “Osilodrostat for cyclic Cushing’s disease,” was published in the journal AACE Endocrinology and Diabetes by two researchers from the UCLA David Geffen School of Medicine in Los Angeles.
All forms of Cushing’s syndrome, the broader disorder, are characterized by elevated levels of the hormone cortisol in the body, which is known as hypercortisolism. In Cushing’s disease, the cause is a tumor on the brain’s pituitary gland. The tumor secretes an excess of adrenocorticotropic hormone, or ACTH, which in turn signals the adrenal glands atop the kidneys to make more cortisol.
Typically, cortisol levels remain high until the underlying cause of Cushing’s is addressed and a person is adequately treated. But in rare cases, hypercortisolism can be cyclical, characterized by spikes in cortisol that intermittently and spontaneously return to normal for days to years before rising again.
Patient treated for cyclic Cushing’s upon third episode of symptoms
Much like all types of Cushing’s, cyclic Cushing’s should be diagnosed and treated early to avoid the complications that can arise from long-term exposure to high cortisol levels. To be diagnosed, a person must experience at least three peaks of hypercortisolism with two periods of normal cortisol in between.
The 68-year-old man in this case was ultimately treated for cyclic Cushing’s when he came to the researchers’ clinic with his third episode of hypercortisolism and related symptoms.
His first two hypercortisolism peaks had occurred at ages 62 and 64. During the second one, he experienced typical Cushing’s symptoms of facial and limb swelling, fatigue, muscle weakness, sleep issues, and a buffalo hump — a buildup of fat between the shoulder blades.
Clinical tests at that time indicated elevated cortisol and ACTH levels. There were no pituitary tumors visible on MRI scans, but further testing suggested that the pituitary gland was the source of excess ACTH.
The man’s symptoms eased spontaneously, and he did not seek treatment again until a few years later, when the third bout of hypercortisolism happened.
At that point, the MRI showed a partially empty sella, where the pituitary gland appears flattened or shrunken. Some of the space the gland would normally occupy in the bony structure that surrounds it was filled instead with fluid.
This imaging finding can make it harder for doctors to see the pituitary gland and identify any tumors on it, in turn complicating a Cushing’s diagnosis.
Indeed, a pituitary tumor still wasn’t evident on the MRI scan, but based on clinical and laboratory findings, the man was still assumed to have Cushing’s disease.
Because a disease-causing tumor couldn’t be identified, however, surgery — normally the first-line option for Cushing’s — was not feasible.
Surgery, the usual treatment, was not an option in this case
The physicians instead started the man on daily Isturisa, a medication used to treat Cushing’s when surgery is not an option or hasn’t worked properly. The medication works to block cortisol production in the adrenal glands.
Here, the treatment worked within 2-3 weeks to ease symptoms and lower cortisol levels. It was discontinued after two months, however, because the man developed adrenal insufficiency, a complication in which the adrenal glands are no longer making enough cortisol.
Still, after three months without treatment, the man’s Cushing’s remained in remission, and adrenal insufficiency did not return, the researchers noted.
Reversible inhibition of cortisol [production] is particularly appealing [in the] treatment of cyclic Cushing’s syndrome as patients will not suffer from prolonged [adrenal insufficiency] after episodes subside. … We thus considered [Isturisa] an attractive treatment [for] cyclic Cushing’s syndrome.
Because the medication’s effects are reversible, it’s not as likely to lead to long-term problems with adrenal insufficiency — a potentially life-threatening complication — as other medications, according to the authors. It can thus be safely used to treat peaks of hypercortisolism as they arise.
“Reversible inhibition of cortisol [production] is particularly appealing [in the] treatment of cyclic Cushing’s syndrome as patients will not suffer from prolonged [adrenal insufficiency] after episodes subside,” the researchers wrote, noting that the medication “showed rapid onset/offset.”
“We thus considered [Isturisa] an attractive treatment [for] cyclic Cushing’s syndrome,” the team concluded.
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