Fat Buildup Impairs Muscle Function in Cushing’s Patients Long After Remission, Study Says

Fat accumulation in muscles caused by Cushing’s syndrome leads to impaired muscle function and worse physical performance long after patients have achieved remission with normal cortisol levels, findings from a new study show.

The study, “Thigh muscle fat infiltration is associated with impaired physical performance despite remission in Cushing’s syndrome,” was published in The Journal of Clinical Endocrinology & Metabolism.

Cortisol is a stress hormone that rises to unhealthy levels in people with Cushing’s syndrome. This can lead to muscle weakness, predominately affecting the lower limbs, which appears to persist in patients even after their cortisol levels reach normal levels.

The amount of fat within muscles (intramuscular fat) is associated with poor muscle function in muscle diseases. Researchers hypothesized that a similar mechanism could be happening in Cushing’s patients, explaining their poor muscle function.

In fact, body fat (including total, visceral, and trunk subcutaneous fat) is significantly increased in Cushing’s patients with active disease, and a study has shown that, despite a reduction in these fatty regions 20 months after remission, patients see no changes in the amount of fatty tissue located between and beneath muscles.

Despite the evidence, no studies have measured the levels of intramuscular fat in Cushing’s patients in remission, or determined whether it correlates with muscle function.

“Whether there is fatty infiltration in the muscles of CS [Cushing’s syndrome] patients after long-term remission, and this is associated with poor muscle function is currently unknown,” the researchers wrote.

In their study, these researchers in Spain assessed the degree of fat infiltration in the thigh muscles of Cushing’s patients in remission for at least three years. They used several physical performance tests to address if and how muscle function correlated with fat infiltration.

The study included 36 women in remission for a median of 13 years. Among them, 28 had Cushing’s disease caused by a tumor in the pituitary gland, and the remaining eight had Cushing’s caused by a benign tumor in the adrenal glands. All patients had undergone surgery to remove their tumors.

When they entered the study, four patients were still receiving hormone replacement therapy for either adrenal or pituitary insufficiency (when the glands are not producing enough levels of one or more hormones).

The researchers also included 36 healthy women (controls), matched to the patients based on their menopausal status and degree of physical activity.

The levels of fat infiltration in thigh muscles were analyzed using magnetic resonance imaging, while muscle strength was assessed with a Handgrip Strength test.

Muscle function and physical performance were measured using multiple tests, including the Gait Speed Velocity (GS) which measures the speed at which patients walk six meters; the Timed Up and Go (TUG) test which measures the time it takes for an individual to rise from a chair, walk three meters, turn around, return, and sit down again; and the 30-Second Chair Stand which measures the number of times an individual can rise from sitting to a full standing position in 30 seconds.

Participants with Cushing’s syndrome had significantly higher amounts of fat in their thigh muscles (20.6% vs. 17.9% in controls), an observation that was also true when anterior and posterior thigh muscles were examined alone. Muscle volume was similar between patients and controls.

The researchers found that Cushing’s patients had worse balance (as measured by the longer TUG times), had less strength in their lower limbs (defined by lower scores in the 30-second Chair Stand), and walked at slower paces in the GS test, suggesting lower functional capacity.

Further analysis revealed that the greater the fat infiltration in the women, the poorer was their performance in several of these tests, even after adjusting for factors known to affect physical performance, such as age, body mass index (a measure of body fat), menopausal status, and muscle volume.

Overall, “our results support the hypothesis that the sustained alteration of physical performance in ‘cured’ CS may be associated with the deterioration of muscle quality due to intramuscular fat accumulation rather than to decreased muscle mass,” the researchers wrote.

“Clinicians should be aware of this sustained deterioration of muscle health, and specifically address this problem during follow-up,” they added. “Future studies are needed to establish the most effective therapeutic strategies to improve muscle weakness in these patients.”