BMD may Underestimate Bone Deterioration for Women with Endogenous Cushing’s Syndrome

Nearly one-third of women with endogenous Cushing’s syndrome and normal bone mineral density have a low trabecular bone score, according to study data.

“A large proportion of patients had degraded microarchitecture despite normal BMD,” Hiya Boro, DM, MD, MBBS, consultant in endocrinology, diabetes and metabolism at Aadhar Health Institute in India, and colleagues wrote. “The risk of fracture may be underestimated if BMD alone is measured. Hence, trabecular bone score should be added as a routine complementary tool in the assessment of bone health in patients with Cushing’s syndrome.”

About one-third of women with endogenous Cushing's syndrome have normal BMD and low trabecular bone score. Data were derived from Boro H, et al. Clin Endocrinol. 2023;doi:10.1111/cen.14944.

Researchers conducted a cross-sectional study at a single center in India from March 2018 to August 2019. The study included 40 women with overt endogenous Cushing’s syndrome and 40 healthy sex-matched controls. Seum and salivary cortisol and plasma adrenocorticotropic hormone (ACTH) were measured. Participants were considered ACTH independent if they had a level of less than 2.2 pmol/L. Areal BMD was measured at the lumbar spine, femoral neck, total hip and distal one-third of the nondominant distal radius. Low BMD for age was defined as a z score of less than –2. Trabecular bone score was measured at the lumbar spine. Fully degraded microarchitecture was defined as a trabecular bone score of 1.2 or lower and partial degradation was a trabecular bone score of 1.21 to 1.34.

Of the 40 women with Cushing’s syndrome, 32 were ACTH-dependent and the other eight were ACTH independent. Of the independent group, seven had adrenal adenoma and one had adrenocortical carcinoma.

Women with Cushing’s syndrome had lower BMD at the lumbar spine (0.812 g/cm2 vs. 0.97 g/cm2< .001), femoral neck (0.651 g/cm2 vs. 0.773 g/cm2< .001) and total hip (0.799 g/cm2 vs. 0.9 g/cm2< .001) than the control group.

“No significant difference was noted in the distal radius BMD,” the researchers wrote. “This may be explained by the fact that cortisol excess predominantly affects trabecular rather than cortical bone.”

Absolute trabecular bone score was lower in the Cushing’s syndrome group compared with controls (1.2 vs. 1.361; P < .001). Based on trabecular bone score, 42.5% of women with Cushing’s syndrome had fully degraded bone microarchitecture, 45% had partially degraded microarchitecture and 12.5% had normal microarchitecture.

“In our study, 32.5% of patients had normal BMD with low trabecular bone score, thus highlighting the fact that patients may have normal BMD despite degraded microarchitecture,” the researchers wrote. “As such, assessment of BMD alone may underestimate the risk of fractures in patients with Cushing’s syndrome.”

Cushing’s Patients at Risk for Autoimmune Diseases After Condition Is Resolved

Children with Cushing’s syndrome are at risk of developing new autoimmune and related disorders after being cured of the disease, a new study shows.

The study, “Incidence of Autoimmune and Related Disorders After Resolution of Endogenous Cushing Syndrome in Children,” was published in Hormone and Metabolic Research.

Patients with Cushing’s syndrome have excess levels of the hormone cortisol, a corticosteroid that inhibits the effects of the immune system. As a result, these patients are protected from autoimmune and related diseases. But it is not known if the risk rises after their disease is resolved.

To address this, researchers at the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) examined 127 children with Cushing’s syndrome at the National Institutes of Health from 1997 until 2017.

Among the participants, 77.5 percent had a pituitary tumor causing the disease, 21.7 percent had ACTH-independent disease, and one patient had ectopic Cushing’s syndrome. All patients underwent surgery to treat their symptoms.

After a mean follow-up of 31.2 months, 7.8 percent of patients developed a new autoimmune or related disorder.

Researchers found no significant differences in age at diagnosis, gender, cortisol levels, and urinary-free cortisol at diagnosis, when comparing those who developed autoimmune disorders with those who didn’t. However, those who developed an immune disorder had a significantly shorter symptom duration of Cushing’s syndrome.

This suggests that increased cortisol levels, even for a short period of time, may contribute to more reactivity of the immune system after treatment.

The new disorder was diagnosed, on average, 9.8 months after Cushing’s treatment. The disorders reported were celiac disease, psoriasis, Hashimoto thyroiditis, Graves disease, optic nerve inflammation, skin hypopigmentation/vitiligo, allergic rhinitis/asthma, and nerve cell damage of unknown origin responsive to glucocorticoids.

“Although the size of our cohort did not allow for comparison of the frequency with the general population, it seems that there was a higher frequency of optic neuritis than expected,” the researchers stated.

It is still unclear why autoimmune disorders tend to develop after Cushing’s resolution, but the researchers hypothesized it could be a consequence of the impact of glucocorticoids on the immune system.

Overall, the study shows that children with Cushing’s syndrome are at risk for autoimmune and related disorders after their condition is managed. “The presentation of new autoimmune diseases or recurrence of previously known autoimmune conditions should be considered when concerning symptoms arise,” the researchers stated.

Additional studies are warranted to further explore this link and improve care of this specific population.

From https://cushingsdiseasenews.com/2018/03/06/after-cushings-cured-autoimmune-disease-risk-looms-study/