Women with adrenal Cushing’s may have lower muscle mass, study finds

Women with adrenal Cushing’s syndrome may have lower muscle mass than those with Cushing’s disease, a study in China suggests.

Researchers found that premenopausal women with Cushing’s caused by a type of adrenal tumor called an adenoma had significantly lower muscle mass relative to their height and less muscle in their legs than those with Cushing’s disease. The adrenal glands sit above the kidneys. Despite having less muscle, these women had lower levels of cortisol, a hormone produced in excess in both conditions.

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Hormone differences may help explain lower muscle mass

The women with adrenal Cushing’s also had lower levels of other hormones, including testosterone, which the researchers suggested may help protect muscles from damage caused by excess cortisol.

Body mass index (BMI), a measure based on height and weight, and the type of Cushing’s were each independently linked to muscle mass, even after accounting for other factors.

The findings may indicate more severe muscle disease in adrenal Cushing’s. They also suggest that “muscle wasting in Cushing’s syndrome represents a multifactorial process,” influenced by the physical load of body weight, differences in hormone levels between the two forms of Cushing’s, and exposure to excess cortisol.

The study, “Worse muscle mass loss in adrenal Cushing syndrome vs. Cushing’s disease: a comparative evaluation of chemiluminescence and LC-MS/MS cortisol assessment,” was published in the Journal of Endocrinological Investigation.

Cushing’s syndrome refers to a group of disorders caused by long-term exposure to too much cortisol, a hormone that helps the body respond to stress.

In Cushing’s disease, the most common form of Cushing’s syndrome caused by problems within the body, a tumor in the brain’s pituitary gland produces too much adrenocorticotropic hormone (ACTH). This hormone tells the adrenal glands to release cortisol. In adrenal Cushing’s syndrome, tumors in the adrenal glands produce excess cortisol without needing ACTH, causing ACTH levels to fall.

Excess cortisol can cause weight gain, particularly around the abdomen, high blood pressure, and difficulty controlling blood sugar, which can lead to diabetes. Muscle weakness and loss of muscle mass are also common Cushing’s symptoms.

While excess cortisol is known to contribute to muscle loss, other hormones, including testosterone, help maintain muscle tissue. ACTH stimulates the adrenal glands to produce cortisol and androgens, a group of sex hormones that includes testosterone. The researchers suspected that differences in these hormones might help explain why muscle mass differs between the two forms of Cushing’s.

Study compares muscle mass in two forms of Cushing’s

To investigate, a team of researchers at Tianjin Medical University General Hospital in China reviewed medical records from 78 premenopausal women with Cushing’s who were evaluated between January 2007 and November 2024. Of these, 37 had Cushing’s disease, and 41 had adrenal Cushing’s caused by adrenal adenomas.

Women in the two groups were generally similar in age, disease duration, and BMI. Rates of diabetes and high blood pressure were also similar.

The researchers assessed muscle mass using a specialized X-ray scan and compared hormone levels between the two groups.

Women with adrenal Cushing’s had a significantly lower muscle mass index, a measure of muscle in the arms and legs relative to height, than those with Cushing’s disease (5.69 vs. 6.16 kg/m²). Leg muscle mass was also significantly lower in the adrenal Cushing’s group (11 vs. 11.8 kg).

Despite having higher muscle mass measurements, women with Cushing’s disease had significantly higher cortisol levels in both blood and urine. They also had higher ACTH and testosterone levels.

More detailed hormone testing in 21 women — nine with Cushing’s disease and 12 with adrenal Cushing’s — found higher levels of several other adrenal androgens in those with Cushing’s disease.

The researchers suggested that higher androgen levels may help protect muscles from some of the damaging effects of excess cortisol. In adrenal Cushing’s, lower ACTH levels may lead to less androgen production, potentially contributing to lower muscle mass.

Body mass index and Cushing’s type linked to muscle mass

Further analyses showed that BMI and the type of Cushing’s were each independently associated with muscle mass index, even after accounting for cortisol levels and disease duration. Cortisol levels, however, were not significantly associated with muscle mass index in this analysis.

The team also compared two methods for measuring cortisol: chemiluminescence, a widely used laboratory method, and liquid chromatography-tandem mass spectrometry (LC-MS/MS), a specialized method that can measure several hormones at once.

In this study, both methods showed a similar, moderate ability to distinguish women with low muscle mass from those without. The researchers suggested that chemiluminescence may “provide a reliable, accessible first-line approach,” while LC-MS/MS offers “unique clinical value” by measuring a wider range of hormones in Cushing’s.

The researchers noted that the study was small, involved women from only one hospital, and did not fully account for factors such as diet and exercise. They said larger studies are needed to confirm the findings.

“Our study found that the muscle mass [within the Cushing’s disease] group was significantly higher than that [of the adrenal Cushing’s] group in premenopausal women,” the researchers concluded. “This may indicate that the [muscle disease] of [adrenal Cushing’s] patients is more serious compared with [that of Cushing’s disease] patients.”