Isturisa managed severe Cushing’s due to advanced adrenal cancer
Patient's condition was treated with a block-and-replace treatment strategy
A 70-year-old woman in the U.S. with Cushing’s syndrome due to advanced adrenal gland cancer who was effectively managed with Isturisa (osilodrostat) was the subject of a report by researchers.
After the woman developed adrenal insufficiency, which is when the adrenal glands become unable to produce sufficient amounts of certain hormones, including cortisol, the woman’s condition was managed using a block-and-replace treatment strategy. This means she was kept on a stable dose of Isturisa to reduce cortisol production, but when her cortisol levels fell into a lower range, hydrocortisone was added to bring them to normal.
“While [Isturisa] is currently only approved for use in pituitary [Cushing’s] disease, we found it effective in off-label use to treat [Cushing’s]  syndrome due to [adrenocortical carcinoma],” the researchers wrote. “With currently limited data available, we hope to see continued examination of [Isturisa] use in non-pituitary [Cushing’s] syndrome.”
The woman’s case was described in the study, “A Case of Severe Cushing Syndrome Due to Metastatic Adrenocortical Carcinoma Treated with Osilodrostat,” published in AACE Clinical Case Reports.
Cushing’s syndrome is marked by high levels of cortisol or hypercortisolism. Cushing’s disease, one of the most common forms of it, is caused by a tumor in the pituitary gland, which produces excessive amounts of adrenocorticotropic hormone (ACTH), a signaling molecule that prompts the adrenal glands to produce cortisol. In rare cases, malignant tumors in the adrenal glands, called adrenocortical carcinomas, cause Cushing’s. These tumors are usually associated with ACTH-independent Cushing’s, that is, forms of the syndrome where excessive cortisol production isn’t driven by ACTH.
Controlling severe hypercortisolism
The woman went to the hospital to be evaluated due to abdominal pain. A CT scan revealed a large tumor in the right adrenal gland.
Lab tests indicated high cortisol levels in her blood and urine. The woman’s ACTH levels, however, were below normal. A dexamethasone suppression test failed to lower her cortisol levels, which is consistent with hypercortisolism.
The woman’s right adrenal gland was removed in surgery and analyzing it led to a diagnosis of stage 2 adrenocortical carcinoma. Three months after surgery, her cortisol levels remained elevated and the cancer’s spread was detected.
The woman started chemotherapy and mitotane, which is marketed as Lysodren and approved to treat adrenocortical carcinoma. It’s also used to lower cortisol levels in Cushing’s. The mitotane was replaced by Isturisa a month later due to hemolytic anemia, that is, anemia driven by the destruction of red blood cells.
As the dosage of Isturisa was increased to bring cortisol levels under control, the woman developed adrenal insufficiency. This was managed with hydrocortisone in a block-and-replace method, meaning Isturisa was maintained to block cortisol production, but when cortisol levels became too low, hydrocortisone was added to raise them.
After eight months with stable urinary cortisol levels, the woman’s cancer spread to her liver and cortisol levels increased. Her clinical condition worsened in the following six months and she was moved to palliative care. She died a short time later.
The researchers said “off-label dosing using a block-and-replace regimen has been described in several cases and appears to be a reasonable option for rapidly controlling severe hypercortisolism.”
“It is also a treatment approach that should be considered when clinical situations result in variable cortisol production such as cyclic Cushing’s syndrome and metastatic [adrenocortical carcinoma],” they wrote.
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