Cushing’s symptoms secondary to tumor ease with Isturisa
Woman, 27, had been diagnosed with metastatic neuroendocrine tumor
A young woman who developed Cushing’s syndrome three years after being diagnosed with a metastatic neuroendocrine tumor saw her cortisol levels decrease and Cushing’s-related symptoms ease after being treated with Isturisa (osilodrostat).
The woman, 27, was started on hydrocortisone when here cortisol levels fell to lower than normal values, and it “continued throughout her treatment course as part of a block-and-replace regimen, given the incurable nature of the underlying disease that causes Cushing syndrome,” the researchers noted.
The woman’s case was described in the study, “Successful Treatment of Severe Ectopic ACTH-Dependent Cushing Syndrome Complicated by Hypocalcemia With Osilodrostat,” published in JCEM Case Reports.
Neuroendocrine tumors arise from cells that release hormones into the blood in response to a signal from the nervous system. In rare cases, these tumors can release excessive amounts of adrenocorticotropic hormone (ACTH), which is normally produced in the pituitary gland and stimulates the adrenal glands atop the kidneys to produce and release cortisol. Above-normal ACTH levels may lead to an overproduction of cortisol and to Cushing’s symptoms.
Blocking, replacing cortisol
The woman developed Cushing’s secondary to a metastatic gastroenteropancreatic neuroendocrine tumor, a rare type of tumor that can form in the pancreas or other organs of the digestive tract. She’d been diagnosed with the tumor three years earlier and had been receiving chemotherapy with cisplatin, etoposide, and durvalamab.
A month before going to an outpatient clinic to be evaluated, she suddenly developed sudden fatigue, muscle weakness, easy bruising, depression, and cognitive impairment.
Lab tests revealed extremely elevated morning levels of cortisol in the blood, as well as in the urine, and high blood ACTH levels. Based on these results and history of cancer, the woman was diagnosed with ectopic Cushing’s, which occurs when the disease is caused by ACTH-producing tumors outside the pituitary gland.
She was hospitalized due to the life-threatening nature of her condition and started on high-dose Isturisa (20 mg, twice daily), which rapidly decreased her morning blood cortisol levels by 46% after five days — from 173.4 to 93.4 micrograms per deciliter.
During treatment, she developed symptoms associated with low cortisol levels, which were managed with hydrocortisone.
Considering her high cortisol levels, called hypercortisolism, removing her adrenal glands was considered, but deemed not feasible. A bilateral adrenal embolization, or blood flow blockage to the adrenal glands, was attempted, but due to complications, was only successfully achieved for the right adrenal gland. Subsequent imaging tests showed her right adrenal gland shrank as a result of the procedure.
After her condition significantly improved, she was discharged on a lower dose of Isturisa (10 mg, twice daily), which was gradually reduced to 5 mg, once daily. She continued treatment with hydrocortisone in a block-and-replace regimen, meaning Isturisa was used to block cortisol production while hydrocortisone was used to replace normal cortisol levels. The woman’s cancer continued to progress and spread to several organs, however.
“Our case report illustrates a complicated case of severe and rapidly progressive hypercortisolism due to [ectopic Cushing’s]. In the context of ineligibility for [adrenal gland removal surgery], use of [Isturisa] at initially high doses quickly reduced cortisol levels and improved comorbidities of hypercortisolism,” the researchers wrote.
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