12376 Comparison Of 1 Mg Versus 2 Mg Dexamethasone Suppression In Obesity

Abstract Disclosure: H. Babu: None. A. Nawaz: None. A.J. Spiro: None. T.D. Hoang: None. M.K. Shakir: None. The overnight 1 mg dexamethasone suppression test (DST) is widely used to screen for Cushing’s Syndrome (CS), especially due to its low incidence of false negative results. Serum cortisol concentrations <1.8 µg/dL suggests adequate HPA axis suppression and usually excludes CS. Concentrations >1.8 µg/dL should be verified with a second test. However, the lack of suppression on DST has been documented previously in 1.46% to 15% of obese patients without CS. Previous studies have suggested simultaneous measurements of serum cortisol, ACTH, and dexamethasone levels after DST to ensure adequate suppression. In this retrospective analysis, we compared the plasma levels of ACTH, dexamethasone, and cortisol levels after 1 mg and 2 mg DST in healthy obese (class III) subjects. The study involved 6 subjects (2 males, 4 females, age 37.5 ± 8.79 years, BMI 43.65 ± 3.12 (kg/m2) who were referred for evaluation of abnormal weight gain. Exclusion criteria for these subjects included diabetes mellitus, pregnancy, history of CS, psychiatric disorders, chronic liver disease, chronic renal failure, malabsorption disorders and nephrotic syndrome. The exclusion of CS was done by history and physical examination showing the lack of specific clinical features of CS. Additionally, none of the subjects were taking drugs that interfered with CYP3A4 or oral contraceptives within 3 months preceding the study. None of the participants reported alcohol consumption of more than 30 g per day. Screening tests for CS involved 1 mg, 2 mg DST, LNSC and 24-hour urine cortisol levels. Results: Following 1 mg DST in 5 subjects, the mean serum cortisol levels were 1.35 ± 0.13 mcg/dL and the mean serum dexamethasone levels, and ACTH levels were 282 ± 44 ng/dL and 5.92 ± 1.56 pg/mL, respectively. However, in one subject (BMI 43.5) the post-DST cortisol level was 2.96 mcg/dL with corresponding dexamethasone level of 138 ng/dL and ACTH level of 21 pg/mL. However, following 2 mg DST in all 6 subjects the serum cortisol levels were less than 1.8 mcg/dL (1.21± 0.22 mcg/dL) with ACTH levels (3.87 ± 0.70 pg/mL) and dexamethasone levels of 482 ± 80 ng/dL. The LNSC levels were normal in 4 subjects (0.010 ± 0.005 mcg/dL), whereas in 2 subjects these were minimally elevated. 24-hour urine cortisol levels were normal in 5 subjects (29.4 ± 3.74 mcg) and in one subject this was mildly elevated (67 mcg). Long term follow-up of all subjects confirmed normal cortisol status. Previous studies have demonstrated that routine CS screening of patients affected by severe obesity is not indicated. However, other investigations have shown CS may occur in a small percentage of severe obese patients. In conclusion, 2 mg DST is a preferred test in obese patients suspected to have CS although 1 mg DST generally can be used as an initial screening test. Additionally, serum dexamethasone and ACTH measurements may still be useful in patients who are suspected to have a false-positive DST. Presentation: 6/1/2024