Abstract Disclosure: J. Saini: None. B. Salama: None. S.R. Chacko: None. K. Yu: None. I. Bancos: None. Objective: Measurement of baseline dehydroepiandrosterone sulfate (DHEAS) is suggested by the guidelines in support of diagnosing mild autonomous cortisol secretion (MACS). However, evidence on the diagnostic accuracy of DHEAS in MACS is difficult to interpret due to differences in the diagnostic cutoffs, small sample size, and heterogeneous reference standards. We aimed to conduct a systematic review and meta-analysis of published literature to assess the performance of DHEAS in diagnosing MACS, as defined in the 2023 guidelines. Methods: A comprehensive search was conducted using several databases from each database’s inception to January 8th, 2024. Databases include Ovid MEDLINE (R) and Epub Ahead of Print, In-Process & Other Non-Indexed Citations, and Daily, Ovid EMBASE, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Databases of Systematic Reviews, and Scopus. Only original studies of at least 20 participants were included. MACS was defined as post-dexamethasone cortisol >1.8 mcg/dL. QUADAS-2 was used to assess the risk of bias. Bivariate and random effects meta-analysis was used to generate pooled diagnostic accuracy estimates. Results: The initial search yielded 285 articles, and only 7 studies met the inclusion criteria. In 7 studies (1 from North America, 3 from Asia, and 3 from Europe), a total of 574 patients with MACS and 830 referent subjects (patients with adrenal tumors without MACS) were included. The mean age was specified only in 5 studies and was similar in patients with MACS (55.5 years) and referent group (53.3 years). Patients with MACS had a higher number of women (323/472, 68.4%) as compared to the referent group (352/658, 53.4%). DHEAS cutoffs studied included: lower cutoff of age-and sex-specific ranges (3 studies), 40 mcg/dL (3 studies), 60 mcg/dL (1 study), and 67.5 mcg/dL (1 study). With increasing DHEAS cutoff, sensitivity for MACS diagnosis increased, and specificity decreased. Most studies (4 studies) used the chemiluminescent immunoassay to measure DHEAS. A meta-analysis of studies using DHEAS cut-off between 40-70 mcg/dL was performed, with a pooled sensitivity of 68% (95% CI: 51-81) and a pooled specificity of 85% (78-89). The positive likelihood ratio was 4 (95% CI: 3-6; I2=36.94, P=0.175) and the negative likelihood ratio was 0.4 (0.3-0.6; I2=49.97, P=0.092). Most studies were at a high risk of bias for selection of patients, index, or reference standard. Conclusion: Based on limited heterogeneous evidence, measurement of DHEAS provides additional value in diagnosing MACS. Further larger diagnostic accuracy studies should explore various DHEAS cutoffs and consider assay variability. Presentation: 6/3/2024
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