Rare Pituitary Carcinoma Managed With Radiation, Chemotherapy
An aggressive tumor in the brain’s pituitary gland, which caused severe Cushing’s disease, was successfully treated with rounds of radiation and chemotherapy with temozolomide, as described in a recent case report.
The study, “ACTH secreting pituitary carcinoma: Rare, durable response to concurrent chemotherapy and re-irradiation with a review of the literature. Recurrent pituitary carcinoma re-irradiation,” was published in the journal Advances in Radiation Oncology.
Cushing’s syndrome is a condition marked by high levels of the stress hormone cortisol. In many cases, it is caused by a tumor in the pituitary gland, which produces greater amounts of the cortisol-controlling adrenocorticotropic hormone (ACTH), and known as Cushing’s disease.
The majority of tumors in the pituitary gland, called adenomas, are benign. In rare cases, pituitary adenomas become aggressive, spread (metastasize), and respond poorly to treatment. These atypical adenomas are called pituitary carcinomas and, in certain cases, arise from ACTH-producing adenomas.
Physicians at the Medical College of Wisconsin described the case of a 53-year-old woman with severe Cushing’s disease due to an ACTH-producing pituitary carcinoma.
The woman came to the hospital with complaints of blurry vision, swelling of the face and extremities, and weight gain over the course of two weeks.
An eye examination revealed she had a type of partial blindness where peripheral vision is lost, and she was submitted to an MRI. The exam found a large mass in a region within the brain called the suprasellar cistern, which is a fluid filled space between the top of the pituitary gland and the bottom of the hypothalamus — a brain region that regulates body temperature, sleep-wake cycles, and appetite, among other functions.
Further tests showed she had high ACTH and cortisol levels that, together with the imaging evidence, confirmed Cushing’s disease caused by a large ACTH-producing pituitary adenoma.
She was submitted to tumor debulking — a procedure in which surgeons attempt to remove as much of a tumor as possible — followed by radiotherapy two months later.
After three years in remission, her symptoms worsened and were linked to high cortisol. She was given cabergoline followed by pasireotide, but failed to improve. Cabergoline, sold under the brand name Dostinex, and pasireotide, sold under the brand name Signifor, are medications that work by lowering the release of ACTH and, ultimately, cortisol.
Imaging scans revealed the tumor had returned and spread, which was consistent with a diagnosis of pituitary carcinoma. She underwent a second surgery to remove the tumor, but her cortisol levels remained high.
The woman’s health declined rapidly within the next two months, with weakness and worsening Cushing’s symptoms.
She enrolled in a Phase 3 trial testing Isturisa (osilodrostat), an approved medication for certain Cushing’s disease patients for whom brain surgery is either ineffective or not an option. But she was unable to tolerate it and was taken off the medication.
Follow-up MRI scans showed evidence of disease progression. The woman was referred to undergo radiotherapy and chemotherapy with temozolomide (marketed as Temodar in the U.S., and as Temodal in Europe and Canada) for 42 days.
Over the next two years, her ACTH and cortisol levels steadily declined, and her symptoms significantly eased. Her cortisol levels, surprisingly, became lower than normal.
Following chemo and radiotherapy, her strength and walking improved, as well as her vision.
A year and a half later, surveillance scans showed a clear shrinkage of the residual tumor compared with prior scans.
Six months later, a new nodule was detected at the clivus, a bony part of the cranium located at the base of the skull. A biopsy confirmed it was a pituitary carcinoma, and she was given radiotherapy.
At the time of the report, the woman remained in clinical remission with stable tumor appearance.
“Here we describe a unique, complete amelioration of severe Cushing’s disease due to an ACTH secreting pituitary carcinoma … after re-irradiation with concurrent temozolomide,” the investigators wrote.
Findings support this therapeutic regimen for “patients with ACTH-secreting [pituitary carcinoma] who fail standard surgical and medical interventions,” they added.