Study Provides Further Evidence of Cognitive, Emotional Difficulties in Cushing’s Syndrome

People with Cushing’s syndrome commonly experience cognitive and emotional problems, a new study indicates.

The study, “Neuropsychological and Emotional Functioning in Patients with Cushing’s Syndrome,” was published in Behavioural Neurology.

Cushing’s syndrome is characterized by abnormally high levels of the hormone cortisol. (Cushing’s disease is a specific form of Cushing’s syndrome caused by a pituitary tumor.)

High cortisol levels can affect the body in a multitude of ways, manifesting as the various symptoms of Cushing’s syndrome. Among these effects, cortisol is known to affect a variety of processes in the brain. Previous research has indicated consistently that Cushing’s syndrome can be associated with changes in cognition, memory, and mood.

Understanding exactly what the common cognitive and emotional manifestations of Cushing’s syndrome are is a burgeoning area of investigation. Better understanding these manifestations could allow for the design of better treatment strategies to address them. There are few published studies on the topic and, due to the rarity of the condition, studies often are limited by fairly small samples.

“The purpose of this study was to examine neuropsychological and psychological functioning in patients with CS with a comprehensive battery of measures,” the researchers wrote. “Given the paucity of literature in this rare clinical group, our goals were to replicate prior findings and identify domains of cognitive deficits and psychological dysfunction in a sample of patients with CS.”

These researchers evaluated cognitive and emotional assessments for 18 people with Cushing’s disease. Most patients (83%) were women and the mean age at evaluation was 41.6 years. Of the 18 people assessed, all but one specifically had Cushing’s disease — the remaining individual had Cushing’s syndrome as a result of adrenal gland abnormalities.

Of note, the evaluated individuals mostly were referred for psychological evaluation because they were complaining of cognitive or emotional symptoms. As such, “The sample may be skewed to overrepresent patients with cognitive or emotional problems and thus limits the generalizability of these findings,” the researchers wrote.

Subjectively, almost all (94%) of the people with Cushing’s syndrome reported problems with attention. Also common were problems with memory (78%), difficulty finding the right words (67%), irritability (50%), impaired processing speed (39%), anxiety (39%), and sadness (39%).

The researchers also assessed scores on a variety of validated cognitive and psychological tests, comparing the scores of the people with Cushing’s syndrome to the average score for people without known medical conditions.

Scores significantly below the norm were considered indicative of “impairment.”  Notably, in a random sample of the overall population, statistically, about 7% of people would be expected to have impaired scores for cognitive measurements, and about 2% would be expected to be impaired for emotional measures.

Relative to the norm values, people with Cushing’s syndrome did not exhibit significant problems with simple attention, working memory, cognitive flexibility, long-term learning or processing speed. However, they showed significant impairment on scores related to sustained attention, short-term learning and visual-spatial processing, with nearly a third of people with Cushing’s syndrome classified as impaired.

The researchers wrote that the reason short-term learning was impaired, but long-term learning wasn’t, could be explained by the difference in sustained attention: “This type of memory profile is highly consistent with the idea that sustained attention difficulties interfere with initial encoding, but that patients are successfully able to consolidate the information that they learned and retrieve the information successfully after a long delay.”

This suggests that it might be important “to educate patients about how attention is sensitive to a variety of lifestyle factors such as fatigue and lack of sleep; proactively managing these areas can help improve attention and memory,” they wrote.

On emotional measures, more than half of the people with Cushing’s syndrome had impaired scores for depression symptoms and somatization (the tendency to overly fixate on uncomfortable physical symptoms). Nearly a quarter had impaired anxiety scores.

“The high rates of anxious and depressive distress are consistent with prior literature,” the researchers wrote, adding, “A multidisciplinary approach that involves mental health and psychiatry is warranted to optimize quality of life in these patients.”

Of the 18 people with Cushing’s syndrome assessed, 11 had active disease, while seven were in biochemical remission. Using statistical models, the researchers compared whether cognitive or emotional problems were more common in either group.

Relative to those in remission, individuals with active disease scored significantly poorer on assessments of processing speed, executive function, and sustained attention. They also reported more somatization and anxiety.

These findings imply that treating the underlying disease may help reduce cognitive and emotional symptoms.