Cushing’s Relapse After Surgery May Be Sign of Cancer Spread
When symptoms of Cushing’s syndrome return after adrenal cancer surgery, this may indicate that tumor cells have spread to other locations, a case report suggests.
The report, “Functioning metastasis from adrenocortical carcinoma,” was published in the journal BMJ Case Reports.
Malignant tumors in the adrenal glands — known as adrenocortical carcinomas (ACCs) — are rare, but may lead to excessive production of cortisol and consequently to Cushing’s syndrome. The adrenal glands are small structures that sit on top of each kidney and are responsible for the production of cortisol and other hormones.
The standard treatment for these cases is bilateral adrenalectomy, or surgical removal of both adrenal glands, followed by intravenous (into-the-vein) chemotherapy with mitotane (marketed as Lysodren), which can be given alone or along with etoposide, doxorubicin, and cisplatin in more advanced cases.
While the main (primary) ACC tumor is commonly a hormone-producing one, few reports have described tumor cells that have spread from the primary tumor into other locations (metastases) to become active, that is, capable of producing and releasing hormones.
Now, a group of researchers in Portugal reported the case of a 56-year-old woman who was admitted to hospital with Cushing’s syndrome due to a cortisol-producing ACC.
She had gained 27 kg (around 59 lbs) in the past six months. This was accompanied by easy bruising, muscle weakness, and uncontrolled high blood pressure (hypertension).
Her clinical history included hypertension, pre-diabetes, high cholesterol, and kidney stones. She also had symptoms of depression.
She had facial redness, high blood pressure, abdominal fat and stretch marks, skin discoloration, as well as a buildup of fat between the shoulders (buffalo hump) and above the collarbones (supraclavicular fat pads) — all signs of Cushing’s.
Lab tests confirmed she had low potassium levels in her blood and high levels of cortisol. Her blood cortisol levels failed to drop after an overnight dexamethasone suppression test, which is used to confirm hypercortisolism by measuring blood levels of cortisol in the morning after patients take a tablet of dexamethasone, a corticosteroid that normally blocks its production. Also, her cortisol levels were not oscillating following the body’s circadian rhythm.
The levels of adrenocorticotropic hormone (ACTH) — the hormone that promotes cortisol production in the adrenal glands — were undetectable in the patient, suggesting she likely had an ACTH-independent form of Cushing’s.
Abdominal CT and later MRI scans revealed two masses in the adrenal glands, without signs of spreading to nearby organs. PET imaging with 18F-FDG PET, an agent used to determine sites of abnormal glucose (blood sugar) metabolism, confirmed they were tumor masses. The PET scan also showed no signs of sugar uptake in other regions.
The patient underwent bilateral adrenalectomy. Tissue analyses of both tumors confirmed the left mass was an ACC, while the right mass was a benign tumor, called an adrenocortical adenoma.
After surgery, the patient’s Cushing’s symptoms eased and she was kept on a corticosteroid combo (hydrocortisone and fludrocortisone) supplementation, which is commonly prescribed for people without adrenal glands.
Her blood pressure remained under control, her potassium levels normalized, and she lost 8 kg (around 18 lbs) in one month. However, two months after surgery, her Cushing’s symptoms reappeared.
She once again developed high blood pressure and gained weight. At this point, corticosteroid replacement therapy was discontinued.
PET scan imaging revealed actively proliferating lesions in her liver and lungs. No signal was detected at the original primary tumor location. Abdominal MRI confirmed the presence of multiple liver metastases.
She underwent chemotherapy with mitotane, but discontinued treatment after one month due to side effects. A multidisciplinary team assembled to discuss other treatment options, and she was started on chemotherapy with etoposide and cisplatin. However, after one cycle, the patient’s health deteriorated markedly and she refused any further aggressive treatment.
The patient was placed under palliative care with metyrapone to control her cortisol levels. The patient died two months after chemotherapy from a generalized body infection due to high cortisol.
“This case demonstrates some interesting features of ACC that pose challenges to its management, including the explosive metastatic growth 2 months after surgery and the potential for fully functional steroidogenesis [hormone production] in late metastases of ACC,” the researchers wrote.
“Clinicians should consider this possibility [functional metastases] if symptoms of hypercortisolism recur after adrenalectomy for ACC and no evidence of local recurrence is found,” they wrote.