Even Slightly High Cortisol Levels Can Have Negative Impact on Mental Health

Even slightly higher-than-normal levels of cortisol — the hormone that is abnormally high in people with Cushing’s syndrome — can have a detrimental effect on mental health, a new study suggests.

The study, “Mental health in patients with adrenal incidentalomas: is there a relation with different degrees of cortisol secretion?” was published in The Journal of Clinical Endocrinology & Metabolism.

Cushing’s syndrome is a disorder characterized by abnormally high levels of cortisol, a hormone that plays a central role in the body’s response to stress. High cortisol levels — or hypercortisolism — can be driven by tumors in the adrenal glands, which sit on top of the kidneys, or in the pituitary gland, a small pea-size master gland found in the brain.

Mental health issues, including anxiety and depression, and cognitive impairments are part of the wide range of symptoms caused by hypercortisolism in people with Cushing’s.

Sometimes, tumors form in the adrenal glands, but they do not cause any overt symptoms. In such cases, it is possible that a tumor will be detected incidentally, as patients undergo other medical evaluations.

Such incidentally discovered adrenal tumors, called adrenal incidentalomas, sometimes cause subclinical hypercortisolism or SH, meaning a slight elevation in cortisol levels, but not overt symptoms related to hypercortisolism. Previous research has evaluated the effect of SH on heart and bone health, but its effect on mental health and cognition has not been thoroughly studied.

To investigate the impact of SH on patients’ mental and cognitive function, researchers in Italy now evaluated 62 people who were diagnosed with adrenal incidentalomas at one of several Italian centers. Among them, 43 also had SH, based on laboratory measurements.

There were no significant differences in age, body mass index, or the use of psychotropic drugs (medications that affect mood, thoughts, or perception) between the individuals with or without SH.

The participants were screened for the presence of psychiatric disorders using a validated semi-structured interview called Structured Clinical Interview for DSM-5 (SCID-5).

In total, 17 of the 62 patients enrolled (27.4%) were diagnosed with a psychiatric disorder, the most common of which was generalized anxiety disorder. No statistically significant differences were found in the prevalence of diagnosed psychiatric disorders between those with or without SH.

A battery of other mental health assessments was conducted with all of the patients. Most found no significant differences between individuals with or without SH. However, there were some exceptions.

Specifically, based on the Sheehan Disability Scale (SDS), patients with SH had significantly higher levels of disability related to mental illness, higher levels of perceived stress, and lower levels of perceived social support, compared with patients without SH.

“Our results confirm and reinforce the idea that even a low degree of cortisol excess may be deleterious for psychological health,” the researchers wrote. They added that such an effect is “explainable considering that cortisol plays a crucial role in the … process of adjustment to stressors and can determine important changes in central nervous system [brain and spinal cord] structures.”

The patients also completed cognitive function assessments. Again, most scores were not significantly different between patients with or without SH, apart from a few exceptions.

“Interestingly,” according to the researchers, the patients with subclinical hypercortisolism scored significantly better on assessments of verbal fluency and symbol coding relative to those without SH. The participants with SH also scored significantly better in the Tower of London Test, which evaluates executive function and planning abilities.

Unlike previous results, these findings are different from what would be expected in people with Cushing’s, where cognition is often impaired. The researchers explained that these findings likely indicate an “inverted U” relationship between cortisol levels and cognition, but noted that this hypothesis would have to be confirmed in future studies.

“Intermediate cortisol levels are associated to a positive hyperactivity of central nervous system [improved cognition], while a further increase of the cortisol levels is associated with a maladaptive response [impaired cognition],” the scientists wrote.

Eight of the patients underwent surgery to remove their tumors. Following surgery, their disability scores on the SDS tended to decrease, indicating lesser disability. However, the difference was not statistically significant.

“Even though we cannot provide a clear-cut idea on the surgical outcome of these patients, in the light of the small sample size and the short follow-up, the finding that the SDS-Disability score slightly improves after surgery suggests a reversibility of the perceived stress in SH patients,” the researchers wrote.

They noted that additional studies using proper control groups, with a larger number of patients and a longer follow-up, would be needed to confirm this possibility.