Spinal fractures can occur early in Cushing’s disease, study finds
Men more likely to have vertebral fractures, per analysis of patient X-rays
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Fractures of the vertebrae (spinal bones) can occur early in the course of Cushing’s disease, according to an examination of chest X-rays of newly diagnosed patients.
Men and those with high morning levels of blood cortisol were more likely to have vertebral fractures, and were also more likely to have more severe fractures.
“Early assessment of [vertebral fractures] should be integrated into routine management of [Cushing’s disease], as skeletal fragility appears to represent an early relevant marker of disease severity,” the researchers wrote.
The study, “Vertebral fractures may occur early in the history of Cushing disease associating with male gender and degree of cortisol secretion,” was published in the journal Pituitary.
Cushing’s disease is caused by a tumor in the brain’s pituitary gland, a small structure at the base of the brain that controls many hormones. This tumor ultimately leads to elevated levels of cortisol, a stress hormone, in the bloodstream.
Fragile bones pose risk
Weak, fragile bones are among the effects of elevated cortisol levels. As a result, fragility fractures, broken bones resulting from minor incidents such as a fall from standing height, are common among people with Cushing’s. This elevated risk persists even after the disease goes into remission.
A recent study found a higher-than-expected number of vertebral fractures among people with newly diagnosed Cushing’s disease. Many study participants, particularly those who had vertebral fractures, had been living with Cushing’s for a long time before it was identified.
The researchers looked into the prevalence of and contributing factors to vertebral fractures in newly diagnosed Cushing’s patients who were still early in the disease course.
The team looked at chest X-rays of 175 adults with newly diagnosed Cushing’s disease, taken before surgery to remove the pituitary tumor. The median disease duration in the group was 12 months, meaning that half the patients had been ill for less than a year. Among the 118 women in the study (67.4%), one-third (33.9%) were postmenopausal.
Many patients had conditions commonly associated with Cushing’s disease, such as type 2 diabetes and impaired fasting blood sugar (36%), obesity (36.6%), high blood pressure (61.7%), and hypogonadism, meaning low levels of sex hormones (35.4%).
Overall, about one in four patients (23.4%) had vertebral fractures. Severity ranged from mild (29.2%) to moderate (39.0%) to severe (31.7%). More than half (56.1%) of those had multiple vertebral fractures, while the rest had a single fracture.
Those with vertebral fractures had a significantly higher median morning blood cortisol level than those without fractures (189.5 nanograms/mL vs. 171.0 ng/mL). Cortisol levels after a dexamethasone suppression test, which checks whether cortisol can be reduced by a synthetic steroid, as in a healthy person, were also higher in the fracture group.
Vertebral fractures were more common among men than women (48.8% vs. 27.6%). Patients with fractures also had a significantly higher rate of hypogonadism (51.2% vs. 30.6%) and significantly lower levels of free triiodothyronine, a hormone produced by the thyroid gland, regardless of sex.
From the data, the team identified a morning blood cortisol level of 173 ng/mL as the optimal cut-off for predicting vertebral fractures in Cushing’s disease, with a predictive power of 61%. A statistical analysis that accounted for multiple factors simultaneously found that being male and having a morning cortisol level above the threshold were each independently associated with vertebral fractures.
In a closer look at those with multiple fractures, median morning cortisol levels were even higher than in patients with a single fracture (230.0 ng/mL vs. 178.0 ng/mL). Multiple fractures were also associated with lower levels of estradiol, the main form of estrogen, and IGF-1, a hormone involved in growth and bone health.
Finally, those with severe fractures were more than twice as likely to be male as those with non-severe fractures (76.9% vs. 35.7%). Severe fractures were also tied to higher morning cortisol and lower IGF-1 levels.
“[Vertebral fractures] may occur in newly diagnosed, short-duration [Cushing’s disease] and are independently associated with male gender and cortisol excess,” the team wrote. “Importantly, [vertebral fractures] also appear to prospectively predict disease severity.”
