Cushing’s symptoms recur after surgery for 1 in 4 patients: Study

Researchers call for 'early clinical intervention' to stop tumors coming back

Margarida Maia, PhD avatar

by Margarida Maia, PhD |

Share this article:

Share article via email
An illustration of doctors looking at a tablet.

About 1 in 4 people with Cushing’s syndrome caused by a tumor saw their symptoms come back after undergoing surgery to remove the tumor, a new study found.

People with Cushing’s disease, which is caused by a pituitary tumor, saw their tumors recur sooner than did those whose Cushing’s was caused by an adrenocortical adenoma, or a tumor in the adrenal glands, the study showed.

The researchers noted that “studying the factors associated with relapse is important,” and found that identifying the cause of a patient’s disease was an independent predictor of Cushing’s symptoms returning after surgery.

As such, “this study provides a basis for early clinical intervention to prevent disease recurrence,” the team wrote.

The study, “Clinical features and risk factors for postoperative recurrence in patients with Cushing’s syndrome of different etiologies,” was published in the journal Scientific Reports.

Recommended Reading
An illustration depicting a person with curly hair writing at a desk, with papers whirling in the air, as the banner image of

I’m grateful Amy Schumer shared her Cushing’s syndrome diagnosis

Cushing’s symptoms back within 9 years after surgery

Cushing’s syndrome is an umbrella term for a range of diseases driven by hypercortisolism, or excess levels of cortisol. Cortisol is a stress hormone produced by the triangle-shaped adrenal glands located on top of the kidneys.

Hypercortisolism can stem from many sources, including noncancerous tumors that form in the pituitary or the adrenal glands, or tumors that form elsewhere in the body but produce ectopic adrenocorticotropic hormone (ACTH), a hormone that triggers the adrenal glands to release cortisol.

Cushing’s may manifest in different ways, depending on the underlying cause. Disease recurrence may mean shorter lives for people with Cushing’s, but the risk factors for symptoms to recur are unknown.

That knowledge gap led a team of researchers in China to analyze the clinical features of patients diagnosed with Cushing’s. Their study involved 202 adults with a median age of 46 at the time of disease onset, who were diagnosed between 2012 and 2022 at The First Hospital of Jilin University. Among the patients, 122 had Cushing’s disease, 71 had Cushing’s caused by an adrenocortical adenoma, and nine had ectopic Cushing’s.

Every patient underwent surgery to remove a tumor. Yet, at a median of 105 months (less than nine years) after surgery, about 25% of patients had seen their symptoms come back. Recurrence was about four times as common in Cushing’s disease patients as in those whose Cushing’s was caused by an adrenocortical adenoma (38% vs. 9%).

Recommended Reading
A risk dashboard with a dial marked with

Tumor removal surgery seen to benefit Cushing’s patients in study

Cushing’s disease, age, tumor size all factors in recurrence

Individuals with Cushing’s disease, patients who were 50 or older, and those who had a tumor smaller than one centimeter in diameter were more likely to experience recurrence sooner, the data showed. There was no difference between men and women in terms of when Cushing’s symptoms returned.

Women accounted for a greater proportion of those with Cushing’s disease or with an adrenocortical adenoma. People with ectopic Cushing’s were a median of 10 years older at the onset of symptoms, but they received a diagnosis 8.5 months sooner.

Hypertension, or high blood pressure, was the most common first symptom in 34% of those with Cushing’s caused by an adrenocortical adenoma, and in 27% of those with Cushing’s disease. People with ectopic Cushing’s were more likely to experience fatigue as their first symptom, with 56% of patients reporting it.

The most common symptoms of Cushing’s were hypertension, seen in 72% of patients; central obesity, or a buildup of fat around the abdomen, experienced by 71%; and diabetes, seen in 35%. While central obesity occurred more frequently in people with an adrenocortical adenoma (82%), diabetes was more common in those with ectopic Cushing’s (67%).

People with ectopic Cushing’s were more likely to experience swelling (78%), fatigue (67%), and infection (44%) than were those with Cushing’s disease or Cushing’s caused by an adrenocortical adenoma.

Among those with Cushing’s disease, 26% each reported swelling and fatigue, while 6% had infections. Some 35% of patients whose Cushing’s was caused by an adrenocortical adenoma experienced swelling, with the same proportion reporting fatigue. A total of 4% had infections.

Nearly half of all patients had hypokalemia, or low levels of potassium, and 15% had hypophosphatemia, or low levels of phosphorus in the blood. Lower levels of potassium and phosphorus were linked to higher levels of cortisol in the blood and urine.

Hypercortisolism can cause changes to the heart. About 22% of patients showed abnormalities in the structure of the heart, including hypertrophy, which occurs when the heart muscle becomes abnormally thick and may cause complications.

Age, cortisol levels before and after surgery, and the number of certain white blood cells were identified as possible risk factors for recurrence.

But only the underlying cause of Cushing’s was found to be an independent predictor for recurrence, according to the researchers.

Thus, the team noted that their findings suggest that etiology, or identifying the cause of the disease, could help predict the likelihood of a tumor coming back after surgery. According to the researchers, this study “is the first to propose etiology as an independent predictor of [Cushing’s syndrome] recurrence.”