Sex Differences in Presentation but Not in Outcome for ACTH-Dependent Cushing's Syndrome

Abstract

Background: Sex differences in clinical picture of ACTH-dependent Cushing's syndrome are controversial, except for the known higher prevalence in females. We compared a broad range of potential differences to enable a more accurate understanding of the clinical picture of sex-specific ACTH-dependent Cushing's syndrome. Methods: Cohort study including consecutive patients with ACTH-dependent Cushing's syndrome from Leiden and Berlin diagnosed between 2000 and 2016. We compared clinical presentation, biochemical parameters, diagnostic tests, surgical outcome, and comorbidities between men and women. Results: We included 130 patients: 37 males and 93 females. With similar cortisol concentrations, ACTH concentrations were higher in males than females at time of diagnosis (median: 116 vs. 57 ng/L). The prevalence of osteoporosis was higher in males than in females (48.6 vs. 25.0%), persisting after surgery, with more vertebral fractures (16.2 vs. 5.4%) before surgery. Males showed more anemia (75.9 vs. 36.8%) after surgery. There were no differences in etiology, pituitary tumor size, diagnostic and therapeutic strategy, or surgical outcome between sexes. Conclusions: Based on this study, males and females with ACTH-dependent Cushing's syndrome present different clinical patterns. However, these differences do not justify different diagnostic strategies or treatment based on sex, considering the similar surgical outcome. Clinicians should be alert to diagnose accompanying osteoporosis (with fractures) in male patients with ACTH-dependent Cushing's syndrome.

Persistent improvement of bone mineral density up to 20 years after treatment of Cushing’s syndrome

“…Interestingly, we found that male sex was associated with lower BMD in CS patients and men more often had vertebral fractures than women. This is in accordance with several other studies that have shown a higher prevalence of osteoporosis in men than in women with CS (10,31,32,33,34). In our study, men were more often hypogonadal compared with women.…”

“…Etiology of CS and gender have been suggested to influence BMD and fracture risk in patients with CS (6,7,9,10,11,12,27,28,30,31,32,33,34). Several studies have shown an association between male sex and lower BMD at diagnosis (10,31,32,33,34). Results on the association between etiology of CS and BMD are conflicting.…”

Central serous chorioretinopathy in active endogenous Cushing’s syndrome

“…CSC is a relatively rare disease, for which an incidence of 9.9 per 100,000 for males and 1.7 per 100,000 for females has been described in a retrospective cohort study 30 . Of note, our study included 4 male CS patients and 7 female CS patients and we observed CSC(like) abnormalities in 2 males and 1 female, despite the fact that CS occurs 5 times more often in females 29 . The incidence of CSC(-like) ophthalmological changes, which occurred in 3 out of the 11 CS patients in our study, may suggest that (subclinical) CSC is more likely to occur in CS patients compared to the general population.…”

“…Notwithstanding, although there is a common trunk of hypercortisolism in CS, it is very interesting to better understand the origin of CS on CSC by studying a larger cohort -probably multicenter. This would also allow for a more comprehensive analysis of risk factors associated with CSC such as gender, or manifestations of CS such as neuropsychiatric symptoms or biochemical (hormonal) abnormalities such as ACTH 29 .…”

Neuroendocrine neoplasia and bone (Review)

“…A cohort study between 2000 and 2019 included 130 subjects with ectopic Cushing syndrome (female/male ratio of 93/37) and it showed that the prevalence of osteoporosis was 25 vs. 48% (females vs. males), while the prevalence of vertebral fractures was 5 vs. 16%, suggesting the fact that actually males are more affected than women when it comes to bone status (92). Moreover, the fracture risk was dependent to some extend on low BMD according to central DXA and/or decreased values of TBS; but the main contributor to fracture risk was found to be the level of hypercortisolemia and the time of exposure, not necessary the pathogenic type of Cushing syndrome or the source of ectopic ACTH over-secretion (meaning that it seemed less important that there was an underling NEN in association with ectopic ACTH production in terms of glucocorticoid osteoporosis) (93).…”