Endocrine Abstracts

Background: Cushing Syndrome (CS) is associated with metabolic disturbances, including obesity. The 1 mg Dexamethasone Suppression Test (1mgDST) is widely used to assess cortisol regulation in suspected CS patients. However, its interpretation may require adjustments based on individual factors, such as body mass index (BMI), due to obesity’s influence on cortisol metabolism. The literature offers differing cutoff values for obese patients. This study aimed to establish BMI-related cutoffs for the 1 mgDST.

Methods: This is a historical-prospective study focused on 1,694 subjects who underwent the 1 mgDST between January 2014 and November 2021. Among them, 1,000 consecutive overweight or obese individuals were included, alongside 100 healthy-weight controls. Exclusion criteria included hypercortisolism, medications affecting dexamethasone metabolism, recent steroid or estrogen use, adrenal masses, and alcohol abuse. Data collection included anthropometric measurements, clinical features indicative of hypercortisolism, medication history, and 1 mgDST results. Waist circumference and waist-to-hip ratio were collected for obese. Body Surface Area (BSA) and BMI were calculated. BMI subgroups were established: healthy weight, overweight, and different obesity classes. Patients failing to suppress cortisol (cortisol >1.8 mg/dl) underwent a second-level assessment involving 0800 hours ACTH sampling, Low-Dose Dexamethasone Suppression Test, and urinary free cortisol tests. Statistical analysis involved group comparisons test, correlation analysis tests, and multivariate logistic regression, and Receiver Operating Characteristic (ROC) curve analysis.

Results: Among the study group, 71 patients did not achieve cortisol suppression after the 1 mgDST. Among them, 39 were excluded from a CS diagnosis based on the second-level evaluation, while 32 were lost to follow-up or declined further assessment. Overweight (n°=96) and obese (n°=772) individuals differed from healthy-weight controls, being older and having more males. Cortisol values after 1 mgDST were significantly lower in overweight/obese patients (median 0.6 vs 0.7 mg/dl; P=0.002). Correlation analyses showed positive associations between cortisol values and age, BMI, BSA, waist circumference, and waist-to-hip ratio, while gender negatively influenced cortisol levels. Multivariate logistic regression highlighted age’s positive independent association with cortisol levels (r=0.012; P<0.0001). ROC curve analysis in overweight/obese patients revealed an optimal cortisol cutoff of 2.1 mg/dl. This threshold remained valid across obesity classes.

Conclusion: This study contributes to establishing BMI-related thresholds for the 1 mgDST, enhancing its diagnostic accuracy in overweight/obese patients. The optimal cortisol cutoff of 2.1 mg/dl proved reliable across various obesity classes, aiding in distinguishing CS from other conditions. Also, age-related variations in test results were observed. Further prospective studies with larger cohorts are required to validate and refine these thresholds.