Ectopic Cushing’s May Occur in Patients With Advanced Thyroid Cancer

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by Patricia Inacio PhD |

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Cushing’s syndrome may develop in people with advanced medullary thyroid cancer and is associated with a poor prognosis, a retrospective analysis suggests.

Severely low levels of potassium in the blood, muscle weakness, and/or diabetes in medullary thyroid cancer patients are signs of ectopic Cushing’s.

The case-series study, titled “Medullary thyroid cancer with ectopic Cushing’s syndrome: A multicentre case series,” was published in the journal Clinical Endocrinology.

Tumors in the brain’s pituitary gland that produce too much adrenocorticotropic hormone (ACTH) are the most common cause of Cushing’s syndrome, which in this case is known as Cushing’s disease. In some cases, however, the disease may be caused by ACTH-producing tumors located elsewhere in the body. In these cases, the disease is known as ectopic Cushing’s syndrome.

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Ectopic ACTH production is mostly seen in lung tumors, but in rare cases, tumors in the thyroid, such as medullary thyroid cancer, may also produce this hormone.

Due to its rarity, the outcomes of these patients are not well-known.

In the case series, a team led by researchers in Germany conducted a retrospective analysis to describe the clinical characteristics, treatment, and prognosis of 11 patients (five men and six women) with medullary thyroid cancer and ectopic Cushing’s syndrome. Patients were treated at three German tertiary care centers and one Swiss center.

The researchers compared these patients’ outcomes to those of 22 people who had medullary thyroid cancer with no signs of ectopic Cushing’s syndrome and who were matched for sex, age, and tumor stage, and served as controls.

Patients were diagnosed with ectopic Cushing’s at a median average age of 59 years. The median average time was 29 months between diagnosis of medullary thyroid cancer and ectopic Cushing’s.

The most common symptoms observed at the time of a Cushing’s diagnosis were muscle weakness and diabetes.

All patients had elevated 24-hour urinary‐free cortisol levels, as well as high cortisol and ACTH levels in the blood.

Their blood cortisol levels did not drop after a low- or high-dose dexamethasone suppression test. This test is usually performed to confirm the presence and determine the cause of high blood cortisol levels. It measures blood cortisol levels in the morning after patients take a tablet of dexamethasone, a corticosteroid that normally blocks its production.

In total, eight of the 11 patients (73%) were treated for Cushing’s with a medicine to suppress cortisol production. Four of them underwent a bilateral adrenalectomy — a surgery to remove both adrenal glands. One patient received treatment with a multityrosine kinase inhibitor to control high cortisol.

Nine patients received add-on therapy to help control Cushing’s syndrome and saw their high cortisol levels (hypercortisolism) and symptoms resolve.

Patients with medullary thyroid cancer and ectopic Cushing’s syndrome had a poorer prognosis (median overall survival of 87 months or about 7.3 years) than patients with cancer alone (190 months or about 15.8 years).

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In total, nine patients died, four due to disease progression and complications of hypercortisolism, including severely low potassium levels in the blood (hypokalemia).

In patients with medullary thyroid cancer, signs of severe hypokalemia along with the onset of muscle weakness and/or diabetes “should raise suspicion for hypercortisolism,” the researchers wrote.

Medicines that inhibit cortisol production and bilateral adrenalectomy were deemed effective therapeutic approaches.