Cushing’s Seen in Woman With Rare Neuroendocrine Tumor in Cervix
The 39-year-old woman's tumor returned many times before a diagnosis
A woman developed Cushing’s syndrome five years after being diagnosed with a neuroendocrine tumor of the cervix, according to a report from the U.S.
This is a rare type of tumor for which “the options for treatment are few and not necessarily curative,” the report’s authors wrote. “Managing the condition can be a challenge and requires a multidisciplinary team approach to improve outcomes.”
The report, “Recurrent Neuroendocrine Tumor of the Cervix Presenting With Ectopic Cushing’s Syndrome,” was published in Cureus.
A neuroendocrine tumor forms from cells that release hormones into the blood in response to a signal from the nervous system. Although it’s rare, it can release higher than normal amounts of adrenocorticotropic hormone (ACTH).
This hormone is usually made in the brain’s pituitary gland during times of stress, driving the adrenal glands on top of the kidneys to produce and release cortisol. Too much cortisol can bring about symptoms of Cushing’s, however.
Diagnosis follows five-year cancer battle
Researchers presented the case of a 39-year-old woman who developed Cushing’s secondary to a small-cell neuroendocrine tumor of the cervix that had came back many times over five years.
A small-cell neuroendocrine tumor is the most common of this type of tumor, but it spreads quickly and usually is associated with a worse outcome, the researchers noted.
The woman visited the emergency room complaining of weight gain, swelling in the face and legs, a tingling sensation in the face, lightheadedness, and a swollen abdomen.
One month before, a CT scan of her abdomen found evidence of metastatic disease, meaning her cancer had spread to other parts of the body. There were multiple lesions in the liver.
A PET scan confirmed the presence of fast-growing lesions in the throat, liver, and lungs. When examined under a microscope, liver lesions were consistent with a neuroendocrine tumor of the cervix.
She was started on anti-cancer treatment with cisplatin, etoposide, and atezolizumab, but developed swelling in the face and abdomen that led her to the emergency room.
A physical examination showed her face appeared rounded and she had a buildup of fat on the back of her neck and shoulders, multiple bruises on her arms, swollen legs, and excessive hair growth on her chin.
Blood tests came back positive for leukopenia (a low white blood cell count) and thrombocytopenia (a low platelet count), which were thought to be side effects of the anti-cancer treatment. She also had high blood sugar levels, a sign of her recently diagnosed diabetes, and hypokalemia (too low potassium levels) and hypophosphatemia (too low phosphate levels).
A MRI scan of the brain came back clear, but a new CT scan revealed new lesions in the lungs and liver. The adrenal glands looked normal.
Treating Cushing’s and cancer
To treat neutropenia, a type of leukopenia where there is a lower than normal amount of a type of white blood cells called neutrophils, the woman was started on antibiotics and filgrastim, a medication that encourages the bone marrow to produce more white blood cells.
After replacement therapy, her potassium and phosphate levels returned to normal and she was started on insulin to keep her blood sugar levels stable.
In response to a low dose (1 mg) of dexamethasone, a steroid medication that can stop the production of cortisol in healthy people, her blood cortisol levels failed to drop. This meant her body was making more cortisol than normal. Cortisol levels in her urine and saliva late at night when they’re normally low were higher than normal. ACTH levels were also high.
Based on these findings, clinicians diagnosed her with ectopic Cushing’s due to a metastatic small-cell neuroendocrine tumor of the cervix. Ectopic means the source of ACTH was not a tumor in the pituitary gland as it happens in Cushing’s disease.
“A biopsy of the liver confirmed a metastatic neuroendocrine tumor, but it is unknown if the other sites of metastases are implicated in the production of excess ACTH,” the researchers wrote.
A surgery to remove the adrenal glands was not done because doctors wanted to treat the tumor metastases first. “Surgery and recovery would delay the start of chemotherapy,” they wrote.
The woman was started on mifepristone (sold as Korlym and other brand names), a medication that lowers blood sugar levels in people with Cushing’s for whom surgery is not an option.
A kidney specialist prescribed oral potassium in combination with spironolactone to lower her blood pressure and a gynecologist put her on bevacizumab, an anti-cancer medication.
After being discharged home, the woman had compression fractures in her lumbar spine (the bones of the lower back) consistent with osteoporosis, a condition that causes bones to weaken and become more prone to fractures. She returned to the hospital multiple times with a neutropenic fever, which occurs with neutropenia.
While her blood sugar and potassium levels remained stable and her body weight and swelling improved, she died a few months later, despite having added topotecan and paclitaxel to her anti-cancer treatment regimen.