Sex Affects Clinical Presentation of ACTH-Dependent Cushing Syndrome

Researchers examined sex differences in clinical presentation and patient outcomes in ACTH-dependent Cushing syndrome.

The clinical presentation of adrenocorticotropic hormone (ACTH)-dependent Cushing syndrome differs between males and females, but this does not affect surgical outcomes, according to study results published in Frontiers in Endocrinology.

The relationship between sex and presentation of ACTH-dependent Cushing syndrome remains controversial. In an effort to better understand these sex differences, researchers aimed to characterize the phenotype of ACTH-dependent Cushing syndrome in a cohort study of male and female patients from Leiden, The Netherlands, and Berlin, Germany, diagnosed between 2000 and 2016.

For 130 patients (71.5% female), diagnosis of ACTH-dependent Cushing syndrome was confirmed using magnetic resonance imaging or computed tomography. First-line treatment was transsphenoidal adenomectomy or removal of the ectopic ACTH-producing tumor in the case of ectopic Cushing syndrome. Outcomes of interest included clinical presentation, surgical outcomes, and short- and long-term morbidity.

At the time of diagnosis, ACTH concentrations were higher for male patients (median, 116 pg/mL) compared with female patients (57 pg/mL). Osteoporosis was also more prevalent in male patients than in female patients (48.6% vs 25%) and male patients were more likely to have a history of fracture (27% vs 19.6%), although neither of these differences were statistically significant after Bonferroni correction. ACTH concentrations and prevalence of osteoporosis remained higher in male patients than in female patients after surgery. There was no difference observed in the etiology of disease or tumor size, histology, or immunohistochemistry between the sexes.

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Postoperatively, anemia was more prevalent in male patients (75.9%) than in female patients (36.8%). Anterior pituitary deficiency was also more prevalent in male patients compared with female patients at both 3 months and 1 year postsurgery. Recurrence was observed more frequently in male patients compared with female patients (28.6% vs 22.1%; hazard ratio, 1.22; 95% CI, 0.52-2.89). In addition, risk for mortality was higher for male patients (hazard ratio, 2.35; 95% CI, 0.73-7.51) compared with female patients.

The researchers noted that the size of the cohort limited the conclusions that could be drawn, and that a larger cohort size would increase the sensitivity of detection of differences between the sexes.

“[M]ale patients with ACTH-dependent [Cushing] syndrome seem to show a different clinical picture than females. However, no different diagnostic strategy or treatment is indicated based on sex, in view of the similar surgical outcome,” the researchers concluded. “Clinicians should pay more attention to male patients with ACTH-dependent [Cushing] syndrome in particular regarding diagnosis and treatment of accompanying osteoporosis (with fractures).”

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Broersen LHA, van Haalen FM, Kienitz T, et al. Sex differences in presentation but not in outcome for ACTH-dependent Cushing’s syndrome. Front Endocrinol. 2019;10(580):1-13.