Glucocorticoids May Decrease White Matter Integrity & Change Gray Matter Volume

I learned many lessons as a rheumatology fellow. Perhaps the most important lesson came from Michelle Petri, MD, MPH, lupus expert extraordinaire. “The p in prednisone stands for poison,” she said.

Although steroids play a significant role in the treatment of many rheumatologic diseases, her point is well-taken. Given The Rheumatologist’s readership, I see no need to review the list of known short- and long-term side effects of glucocorticoids. It’s long. A study in BMJ Open just made the list longer.¹

In August 2022, Merel van der Meulen, BSc, MD, PhD candidate, Department of Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, The Netherlands, and colleagues share data demonstrating that the use of both systemic and inhaled glucocorticoids is associated with changes in several brain imaging parameters.¹

Background

Glucocorticoids are associated with a variety of neuropsychiatric symptoms and disorders, including—but not limited to—depression, mania and delirium.² What’s more, several studies have demonstrated the anatomical effects of glucocorticoids on the brain. Example: Cushing disease (i.e., chronic endogenous glucocorticoid excess secondary to a pituitary tumor) is associated with global cerebral atrophy, as well as decreased cortical thickness and gray matter volume in specific areas of the brain.^3,4

Studies investigating glucocorticoid overexposure and brain structure are small, and none have included subjects taking inhaled glucocorticoids. Van der Meulen et al. used data from the U.K. Biobank—a population-based prospective cohort containing in-depth genetic and health information from over half a million U.K. participants aged 40–69 at the time of recruitment. The researchers investigated whether differences in brain volumes and white matter microstructure could be detected between users and non-users of systemic or inhaled glucocorticoids.^1,5

The primary outcome of the study was the difference in imaging parameters between glucocorticoid users and non-users for brain regions of interest previously shown to be affected by long-term glucocorticoid exposure. Secondary outcomes included differences in cognitive and emotional functioning between glucocorticoid users and non-users.

‘This study may raise awareness for the potential psychiatric side effects associated with glucocorticoid use.’ —Dr. Van der Meulen

Summary of Research

Van der Meulen et al. examined patients taking systemic (n=222) or inhaled (n=557) glucocorticoids at the time of both T1-weighted magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI). DTI characterizes microstructural changes and differences due to neuropathology and treatment.⁶ The study subjects also completed a series of cognitive tests and mental health questionnaires that assessed symptoms experienced over the preceding two weeks while taking glucocorticoids.