Prolonged Cortisol Exposure Can Affect Long-term Quality of Life

Study suggests excess cortisol may lead to changes in brain reward circuitry

Lindsey Shapiro, PhD avatar

by Lindsey Shapiro, PhD |

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Prolonged exposure to the hormone cortisol during periods of active disease in Cushing’s patients is linked to lower long-term quality of life but not to cognitive problems after remission, a study shows.

The study, “Impaired quality of life, but not cognition, is linked to a history of chronic hypercortisolism in patients with Cushing’s disease in remission,” was published in the journal Frontiers in Endocrinology

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Cushing’s disease is characterized by excess cortisol, or hypercortisolism, in the body, typically as a result of tumors in the brain’s pituitary gland.

Cognitive difficulties are one of symptoms of Cushing’s disease. Often, cognition improves once the disease is in remission following treatment, but for some patients, symptoms persist even after cortisol levels have been controlled.

Prolonged and excessive brain exposure to cortisol during periods of active Cushing’s disease may have lasting effects that explain the ongoing impairment, which in turn leads to long-term declines in quality of life.

But several other confounding factors, such as advanced age, obesity, or medication use, could also have an influence. Few studies have investigated cognitive outcomes among Cushing’s patients in remission while accounting for all these factors.

Here, researchers reported data from a study (NCT02603653) to determine if Cushing’s patients who were in remission had cognitive problems even in the absence of other factors.

Included in the study were 25 patients (19 females and six males, with a mean age of 44.5 years), who were seen at two centers in Bordeaux, France, and Barcelona, Spain. All patients had been in remission for at least one year (an average time of 102.7 months, or about 8.5 years). Also, 25 age-matched healthy participants were included.

Participants had none of a range of clinical characteristics thought to influence cognition, including advanced age (over 60 years), obesity, uncontrolled health problems like diabetes or high blood pressure, certain hormonal abnormalities, or a history of neurological problems.

Use of certain medications that could influence brain function, or medications to induce Cushing’s remission were also excluded, as was a history of pituitary radiation, another treatment approach.

The participants underwent a battery of cognitive tests, and quality of life was assessed with the generic Short Form 36 (SF-36) questionnaire and the CushingQoL questionnaire.

Clinical scores for Cushing’s symptoms were minimal at the time of testing, suggesting that patients had few residual signs of the disease.

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Across cognitive tests, patients were generally similar to healthy controls in cognitive performance.

That finding “challenges the concept of irreversible memory impairment due to a specific and direct effect of hypercortisolism in patients below the age of 60,” the researchers wrote, adding that “various persisting co-morbidities of [Cushing’s disease] may be responsible for long-lasting impaired memory and should therefore be actively sought and adequately treated by expert specialists.”

In contrast, patients had lower scores on most SF-36 subscales, reflecting quality-of-life impairments. Specifically, patients had lower scores in the physical function, role-physical, general health, and vitality domains of the questionnaire.

The duration of hypercortisolism during active Cushing’s disease was associated with scores in the SF-36 general health, vitality, role-physical, and physical function subscales, and in the CushingQoL questionnaire. Generally, a longer exposure to hypercortisolism — or a longer time between Cushing’s symptom onset and remission — was linked to greater impairments in these domains.

Patients also scored lower than controls on the Depression Rating Scale, but no differences were observed in the Hospital Anxiety and Depression Scale.

“The contrast between lasting impairment of [quality of life] on the one hand and absence of major physical, psychological and cognitive sequelae [or disease outcomes] on the other hand, may reflect irreversible consequences of cortisol excess,” the researchers wrote.

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The brain’s exposure to excess cortisol could lead to changes in its reward circuitry, much like that observed during drug abuse, the team suggested.

“One could hypothesize that prolonged impaired [quality of life] may share common mechanisms with those observed following withdrawal from drug abuse,” the researchers wrote.

The study is limited by its small sample size, “a problem practically unavoidable in rare diseases,” the team noted. Nonetheless, “the association of negative health perception and impaired [quality of life] with the duration of cortisol excess reinforces the importance of shortening this exposure, especially following diagnosis, to reduce the long-term burden of [Cushing’s disease].”