Despite Falling Mortality Rates, Cushing’s Still Triples Risk of Death

Although mortality rates associated with endogenous Cushing’s syndrome have dropped in recent years, the disease is still linked to a threefold increase in the risk of death, mainly from cardiovascular issues and infections, a recent analysis of past research has found.

“Our results found that death rates have fallen since 2000 but are still unacceptably high,” Padiporn Limumpornpetch, MD, an endocrinologist from Prince of Songkla University in Thailand, and the study’s lead author, said in a press release.

These findings “highlight the need for aggressive management of cardiovascular” and other issues among Cushing’s patients to reduce the risk of death, Limumpornpetch said.

The analysis’ findings were presented recently at the virtual ENDO 2021, the Endocrine Society’s annual meeting, in a presentation titled “Mortality and Specific Causes of Death in Endogenous Cushing’s Syndrome: A Systematic Review, Meta-Analysis and Meta-Regression.”

Endogenous Cushing’s syndrome occurs when the body produces too much cortisol, either because of a tumor in the brain’s pituitary gland — then called Cushing’s disease — or due to a tumor in the adrenal glands that sit atop the kidneys, which is known as adrenal Cushing’s syndrome.

Left untreated, the condition causes a considerable health burden, including “excess mortality,” the researchers noted. There is little data, however, detailing the specific causes of death.

According to the investigators, such information could help guide medical care.

To learn more, a team from the University of Leeds, in the U.K., and the Belgian Cancer Centre, in Belgium, analyzed all available past studies that reported deaths involving Cushing’s syndrome caused by either Cushing’s disease or adrenal Cushing’s.

A total of 87 studies were found that met the criteria. These studies covered 100 cohorts — sets of patients analyzed as a group — of which 53 involved individuals with Cushing’s disease, 27 included people with adrenal Cushing’s, and 20 involved those with both disease types.

The number of observed deaths across all study groups was nearly three times (2.91) that of the number of expected deaths among healthy people of the same age and sex. Comparatively, the ratio for Cushing’s disease alone was higher, at 3.27, and that for adrenal Cushing’s was slightly lower, at 1.62.

On average, the overall mortality rate was measured at 5%, while that of Cushing’s disease alone was at 4% and that of adrenal Cushing’s was at 6%. Mortality ratios also were higher among patients with active disease, compared with those who were in remission.

Patients’ tumors in all Cushing’s cases are generally removed surgically, and the rate of death in the 30 days following these surgeries has fallen to zero since 2011, the analysis found. Limumpornpetch attributed this drop to better medical care, and to advances in diagnostic and surgical techniques.

Before 1991, deaths occurred in 7% of patients during the 30-day post-surgery window. That number decreased to 3% between 1991 and 2000, and to 1% between 2001 and 2010. Following that time point, deaths have since fallen to zero.

Across 64 studies reporting causes of death, the most common were cardiac-related (24.7%), followed by infection (14.4%), diseases involving brain blood vessels (9.4%), and cancer (9.0%). The cause of death was blood clot disorders in 4.2% of patients, active disease in 2.9%, and adrenal insufficiency in 2.7%.

“The causes of death highlight the need for aggressive management of cardiovascular risk, prevention of [blood clots] and good infection control and emphasize the need to achieve disease remission, normalizing cortisol levels,” said Limumpornpetch, who is also a PhD student at the University of Leeds.