Irisin Hormone Levels May Help Diagnose Muscle, Bone Weakness

Patients with active Cushing’s disease have lower blood levels of irisin, a hormone secreted by muscle cells, than those with controlled disease and healthy people, a study has found.

Thus, measuring the levels of irisin may become a marker for diagnosing impairments of bone, muscle, and fat (adipose) tissues in this patient population, researchers suggest.

Such a marker would be helpful for identifying a condition called sarcopenia — characaterized by muscle weakness and loss — that is often seen in people with Cushing’s disease.

The study, “Circulating Irisin Levels as a Marker of Osteosarcopenic-Obesity in Cushing’s Disease,” was published in the journal Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy.

Sarcopenia many times occurs in Cushing’s patients as a consequence of the abnormally high levels of the hormone cortisol that characterize the disease. Its occurrence often is associated with obesity and osteoporosis, and results in a condition called osteosarcopenic obesity.

The levels of irisin, a hormone secreted from the skeletal muscle, have been correlated in previous studies with the risk of sarcopenia, as well as with effects on the metabolism of bone, adipose tissue and glucose (blood sugar).

Since cortisol acts on these tissues, researchers hypothesized that “changes in irisin levels may be correlated with cortisol excess.”

To learn more, researchers now measured the levels of irisin in the blood of patients with active Cushing’s disease and in those who had achieved remission, as well as in healthy individuals (controls). Additional metabolic parameters, including body mass index (BMI) and waist circumference (WC) — both measures of body fat — also were evaluated.

A total of 44 people with Cushing’s disease — 35 women (80%) and nine men, with a mean age of 48.5 — were recruited at Palermo University, in Italy. The analysis also included 40 age and sex-matched healthy controls. Notably, the controls had been “referred with a suspicion of [Cushing’s syndrome], subsequently ruled out by repeated biochemical assessments,” the researchers wrote.

In people with Cushing’s disease, the analysis was performed during active disease and the again 12 months after remission. To evaluate muscle health, participants performed the chair rising test, in which they’re asked to rise from a sitting position on a chair as fast as possible.

The analysis revealed that myopathy, or weak muscles, and metabolic abnormalities were higher in patients with active Cushing’s disease as compared with those in remission and with controls. BMI and WC scores, as well as the levels of the parathyroid hormone (PTH) also were elevated in active disease patients compared with controls and with patients in remission.

Blood levels of irisin were significantly lower in those with active Cushing’s disease (mean 4.51 nanograms per mililiter, ng/ml) relative to the controls (mean 13.4 ng/ml) and to patients with controlled disease (6.57 ng/ml). The researchers noted that the levels of irisin in people with controlled disease, while higher than those of the patients with active Cushing’s, were still lower in comparison with those of the controls.

These findings suggest that high cortisol levels seen in active Cushing disease “induce a decrease of circulating irisin levels,” while “remission of hypercortisolism [high cortisol] is able to increase circulating irisin values,” the researchers wrote.

Lower levels of irisin, as seen in people with active and controlled disease, correlated with an increase in measures of body fat — namely WC — and those of PTH and myopathy. Such lower levels also were tied to a worse performance in the rising test. The researchers

Elevated levels of PTH in the blood also have been linked with a reduction of bone mass density, supporting a potential link between irisin and bone mass via PTH, the researchers noted.

Overall, these findings suggest that “circulating irisin levels tend to be lower in patients with CD [Cushing disease] before and after correction of hypercortisolism compared to controls,” the researchers wrote.

The levels of irisin in the blood could thus serve as a molecular biomarker for muscle weakness and bone mass loss, as well as central obesity in these patients, the team concluded.