Clinical Profile, Biochemical Characteristics, and Surgical Outcomes in Cushing Disease: An Age-Stratified Analysis of a Large Tertiary-Care Cohort.

Abstract

Objective: To characterize the clinical, biochemical, radiological, and surgical profile of Cushing disease in a large tertiary-care cohort, with emphasis on age-stratified differences.

Methods: This retrospective observational audit included 277 patients with confirmed Cushing disease managed at a high-volume tertiary-care center between 2006 and 2025. Baseline clinical, biochemical, metabolic, radiological, and outcome data were extracted from the time of initial evaluation at our center, generally during diagnostic confirmation and before definitive therapy. Hormonal parameters were assessed using electrochemiluminescence immunoassay, and bone mineral density was evaluated using dual-energy X-ray absorptiometry only in a clinically selected subset. Surgical outcomes were assessed based on early postoperative cortisol levels, with remission defined as morning cortisol < 138 nmol/L.

Results: The cohort demonstrated a marked female predominance (71.8%), with most patients presenting in the third and fourth decades. Classical cushingoid features were highly prevalent, including weight gain (79.4%), centripetal obesity (62.5%), hyperpigmentation (61.0%), and proximal myopathy (60.6%). Exploratory age-stratified patterns were observed in selected clinical and biochemical variables. Younger patients showed a relatively higher recorded frequency of dermatological and reproductive manifestations, including striae, acne, and menstrual irregularities, whereas the recorded burden of cardiometabolic comorbidities at tertiary-care assessment, including hypertension (70.8%) and diabetes mellitus (48.0%), was higher in older age groups. Body mass index and blood pressure also varied across age groups, although these findings should be interpreted cautiously because of the retrospective design, unequal age-stratum sizes, and absence of adjustment for multiple comparisons. Biochemically, median cortisol levels were elevated across the cohort, with exploratory variation across age groups. Higher cortisol concentrations were observed in younger patients, while adrenocorticotropic hormone levels remained comparable across age decades. Bone mineral density was available in a clinically selected subset of 78 patients. Within this DXA subset, reduced bone density was frequent; however, these findings were not extrapolated to the entire cohort. Transsphenoidal surgery was the primary treatment modality. Numerically similar early remission proportions were observed in microadenomas (72.7%) and macroadenomas (72.2%) in this cohort, with no clear descriptive age-related pattern in early postoperative outcomes. Early biochemical remission was observed in 166/233 surgically treated patients (71.2%), while 67/233 patients (28.8%) had persistent disease. Relapse was assessed only after documented initial remission and occurred in 22/166 patients (13.3%).

Conclusion: This large single-center cohort demonstrates substantial recorded clinical and cardiometabolic burden at tertiary-care assessment in Cushing disease. Exploratory age-stratified patterns were observed in clinical phenotype and cortisol profile, while numerically similar early remission proportions were observed across tumor-size categories in descriptive analyses. Bone-density findings apply only to the DXA subset, and non-uniform follow-up limits robust assessment of long-term recurrence.