Men with Cushing’s may be at higher anemia risk after surgery
Study finds dynamics of red blood cells altered in patients, varying by sex
Men with Cushing’s syndrome may be at an increased risk of developing anemia (low red blood cell counts) in the months following surgery to remove a disease-driving tumor, a recent study suggests.
Researchers found red blood cell dynamics are altered in people with Cushing’s syndrome, and the specific patterns of these alterations vary according to biological sex.
The study, “Erythropoiesis in Cushing syndrome: sex-related and subtype-specific differences. Results from a monocentric study,” was published in the Journal of Endocrinological Investigation.
Cortisol known to affect development and activity of red blood cells
Cushing’s syndrome is a broad term for disorders in which symptoms are driven by elevated levels of the hormone cortisol. Cushing’s disease is a specific form of the syndrome caused by a tumor in the brain’s pituitary gland.
Cortisol is known to affect the development and activity of red blood cells, which are responsible for transporting oxygen through the bloodstream. Some studies have suggested that red blood cell dynamics may be altered in people with Cushing’s syndrome, but the details remain unclear.
To learn more, a team led by scientists at the University of Würzburg in Germany conducted an analysis of data on 210 people with Cushing’s syndrome who were treated at their center between 2000 and 2022. Among the patients, 40% had Cushing’s disease, while the remainder had other forms of Cushing’s syndrome.
The researchers also identified a set of more than 200 people with pituitary or adrenal tumors that were not hormonally active, meaning they did not cause Cushing’s. The two groups were matched according to age and sex. Participants’ on average were in their late 40s and about three-quarters were women.
While increased [red blood cell volume percentage] levels do not result in more major cardiovascular events in women, the risk of anemia in men needs to be carefully evaluated, especially during the first months after remission.
Male and female patients were analyzed separately
The researchers conducted statistical tests to compare red blood cell parameters in patients with or without Cushing’s. Since hormonal differences between sexes can affect red blood cell development, male and female patients were analyzed separately.
Among female patients, those with Cushing’s disease had a significantly higher volume percentage of red blood cells, larger red blood cells, and higher levels of hemoglobin — the protein in red blood cells that’s responsible for transporting oxygen. These increases showed no apparent association with an increased risk of heart-related health problems, the researchers noted.
The average size of red blood cells was also elevated in male patients with Cushing’s syndrome. However, in male patients, those with Cushing’s had a significantly lower volume percentage of red blood cells, as well as significantly lower hemoglobin levels.
The researchers described a “relevant sexual dimorphism” characterized by an increase in red blood cell volume percentage and hemoglobin levels in women with Cushing’s syndrome whereas men with Cushing’s showed lower levels.
Among men with Cushing’s, lower red blood cell parameters were found to be associated with lower levels of testosterone, the main male hormone. These results suggest that reproductive health “status in men could have a major influence on hematologic [blood-related] function,” the researchers wrote.
Red blood cell parameters tended to decrease following curative surgery
Analyses also showed red blood cell counts and hemoglobin levels were significantly higher among female patients with Cushing’s disease than in those with ectopic Cushing’s syndrome. However, no statistically significant differences in red blood cell parameters were found among male patients with different forms of Cushing’s syndrome.
“Although the idea that [red blood cell] analysis may allow for a first subtype differentiation in cases with [Cushing’s syndrome] subtypes is intriguing, this finding has to be confirmed in larger populations,” the researchers wrote.
Among patients with available data, red blood cell parameters tended to decrease in the months following surgery to remove a disease-driving tumor. A decrease was seen in female patients who generally had increased red blood cell parameters before surgery, as well as in male patients with lower levels before surgery.
“While increased [red blood cell volume percentage] levels do not result in more major cardiovascular events in women, the risk of anemia in men needs to be carefully evaluated, especially during the first months after remission,” the team wrote.
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