Bone and Blood Vessel Problems Can Be Common With Cushing’s

Cortisol, at excessive levels in patients, affects bone-vascular axis

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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People with Cushing’s syndrome are at an increased risk of developing problems related to their bones or blood vessels due to excessive cortisol, a study highlighted.

Problems in both these areas — the bones and the blood vessels — can also co-occur, its scientists reported.

The study, “Coexistence of bone and vascular disturbances in patients with endogenous glucocorticoid excess,” was published in the journal Bone Reports.

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Cushing’s syndrome encompasses a group of conditions characterized by unusually high levels of cortisol, a hormone the body produces in response to stress. Cushing’s disease is a specific form of the syndrome in which excess cortisol levels are caused by a tumor in the brain’s pituitary gland.

Spinal fractures, stiff arteries more common in Cushing’s patients

Among its many functions throughout the body, cortisol is known to affect the bone-vascular axis — a group of molecular signaling pathways that, as the name suggests, are important for regulating bone and blood vessel health. Despite this established link, it is not clear whether excess cortisol levels increase the risk of bone- or blood vessel-related health problems in people with Cushing’s.

To learn more, a team of scientists at Kyushu University in Japan conducted an analysis of 194 people.

Half had excess cortisol levels, including 17 with overt Cushing’s syndrome and 80 with subclinical Cushing’s (elevated cortisol levels, but no overt disease symptoms), all of whom had adrenal tumors.

The other half, included as a control group, had non-functional adrenal tumors, meaning tumors that did not produce hormones, and normal cortisol levels. Of note, the adrenal glands sitting atop the kidneys are the ones responsible for cortisol production; tumors in these glands may cause them to overproduce cortisol, which can lead to the onset of Cushing’s.

The two groups were similar in terms of age, sex, menopausal status, body mass index, alcohol intake, and smoking status. Rates of diabetes mellitus, high blood pressure, and hyperlipidemia (high levels of fatty molecules in the blood) were higher among Cushing’s patients than controls.

Rates of vertebral fractures — broken bones in the spine — were significantly higher among Cushing’s patients than controls (49% vs. 8%). Cushing’s patients also had markedly lower density in several bones, though signs of overt bone loss were rare in both groups.

More Cushing’s patients than controls had arterial stiffness (37% vs. 21%) or abdominal aortic calcification (32% vs. 15%), both of which are signs of blood vessel disease.

Nearly 1 in 4 Cushing’s patients had both vertebral fracture and arterial stiffness (23%) or vertebral fracture and abdominal aortic calcification (22%). Among controls, the percentage of individuals with these co-occurring conditions was 2% and 1%, respectively.

“These observations suggested that excess endogenous cortisol leads to the progression of bone and subclinical vascular diseases simultaneously,” the researchers wrote.

Additional analyses, conducted after a dexamethasone suppression test, found cortisol levels to be higher in patients with co-occurring vertebral fracture and arterial stiffness, regardless of Cushing’s status. Cortisol levels were also seen to significantly correlate with certain markers of bone and blood vessel health in patients.

“This study has clinical implications for the management of patients with [Cushing’s]. Particularly, patients with arterial stiffness may have deteriorated bone quality, even without decreased bone mass,” the scientists wrote.

Researchers noted that this study is limited by its small size and single-center design, calling for additional research to validate its results. The team also noted these findings may not be generally applicable to Cushing’s disease patients, since their pattern of steroid hormone production differs from that of patients with adrenal tumors.

“Cushing’s disease and adrenal CS [Cushing’s syndrome] may have different coexistence rates of bone and vascular disease,” the scientists wrote.