Hormones may explain Cushing’s disease bone density differences
Reduced density seen for women with adrenal Cushing's syndrome: Study
Differences in the levels of hormones made by the adrenal glands, which sit atop the kidneys, may explain why bone density is less affected in women with Cushing’s disease than in female patients with other forms of Cushing’s syndrome, a new study from researchers in China reports.
Their results showed significantly reduced bone density in women with adrenal Cushing’s syndrome, or ACS — when the disease is caused by tumors in the adrenal glands themselves — than in those with Cushing’s disease. Reduced bone density is a sign of osteoporosis, a symptom seen in both men and women with different forms of Cushing’s.
“This research mainly introduces the clinical characteristics of bone metabolism in premenopausal female patients with [Cushing’s syndrome] and its manifestations in different subtypes,” the researchers wrote. “These findings enhance our understanding of how adrenal … hormones influence bone mass and contribute to the pathogenesis [disease development] of osteoporosis in patients with [Cushing’s disease].”
The study, “Hormones synthesized by the adrenal reticulum protect bone density in premenopausal women with Cushing syndrome,” was published in the journal Bone.
Bone density analyzed in 75 women with Cushing’s disease or ACS
Cortisol is a hormone made by the adrenal glands, and produced in response to stress. Excessively high cortisol levels, or hypercortisolism, can lead to a variety of health problems, such as mood issues, weight gain, and weakened bones.
Cushing’s syndrome is a broad term referring to conditions driven by hypercortisolism. Cushing’s disease is a specific form of the syndrome in which a tumor in the brain’s pituitary gland leads to the overproduction of a signaling molecule that stimulates the adrenal glands to produce excessive amounts of cortisol.
Previous studies have suggested that people with Cushing’s disease are less likely than those with adrenal Cushing’s syndrome to develop weakened bones as a complication of their condition. But it hasn’t been clear why this difference exists, especially because hypercortisolism is assumed to be the main cause of bone issues in both diseases.
To gain further insight, the scientists analyzed cortisol levels and bone density in 75 premenopausal women — 33 with Cushing’s disease and 42 with ACS.
In line with earlier data, the results indicated that patients with ACS tended to have lower bone density, especially in the hipbone and lower spine. Paradoxically, however, patients with Cushing’s disease had higher cortisol levels in the blood and urine than those with ACS.
Digging deeper, the scientists conducted more extensive hormone profiling on a subset of patients.
“Although cortisol is a key factor, it is insufficient to explain bone health entirely,” the researchers wrote. “Other steroid metabolites might have an impact on bone health in Cushing syndrome patients.”
Our study found that premenopausal women with [adrenal Cushing’s syndrome] had lower levels of adrenal [hormones] and significantly reduced [bone density] compared to those with [Cushing’s disease], despite higher cortisol levels in the [Cushing’s disease] group.
The study’s results showed that, in addition to having higher cortisol levels, patients with Cushing’s disease tended to have higher levels of other hormones that are made by the adrenal glands. This was seen with both dehydroepiandrosterone, known as DHEA, and dehydroepiandrosterone-sulfate, or DHEAS.
Statistical analyses showed a strong correlation between the levels of these hormones and bone density; in other words, patients with higher levels of these adrenal hormones tended to have stronger bones. As such, the researchers argued that alterations in the levels of these other hormones might explain why people with Cushing’s disease are less likely than those with ACS to experience bone issues.
“Our study found that premenopausal women with ACS had lower levels of adrenal [hormones] and significantly reduced [bone density] compared to those with [Cushing’s disease], despite higher cortisol levels in the [Cushing’s disease] group,” the team wrote. “Notably, elevated levels of DHEA and DHEAS were independently associated with increased [bone density] in both ACS and [Cushing’s disease] patients, suggesting a protective effect against bone loss.”
According to the researchers, study limitations included the small sample size, the fact that only premenopausal women were assessed, and the fact that hormone levels and bone density were measured just once and not tracked over time. The team highlighted a need for further studies to delve deeper into the role of these hormones in bone health in Cushing’s and to see if the findings also apply to other patient populations.
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