Singh, R J

Abstract Disclosure: K. Yu: None. S. Athimulam: None. J. Saini: None. R. Kaur: None. R.J. Singh: None. S.K. Grebe: None. Q. Xue: None. I. Bancos: Advisory Board Member; Self; AstraZeneca, Corcept, Novo Nordisk, HRA Pharmaceuticals, Neurocrine, Diurnal, Recordati, Sparrow, Xeris, Spruce, Adrenas. Research Investigator; Self; HRA Pharmaceuticals, Recordati. Context: Early diagnosis is essential to assure a better prognosis in patients with adrenocortical carcinoma (ACC). Guidelines suggested performing urine steroid profiling in patients with indeterminate adrenal tumors to make a noninvasive diagnosis of ACC. However, urine steroid profiling is not widely available. Accuracy of clinically available serum steroids in diagnosing ACC has not been established. Objective: To determine the accuracy of 11-deoxycortisol, 17OH-progesterone, and 17OH-pregnenolone in diagnosing ACC. Design: Prospective single-center cohort study. Participants: Between 2015 and 2023, consecutive patients with adrenal mass were prospectively enrolled in the prospective registry and biobank study. Patients who agreed to contribute a fasting serum sample were included in the study. Exclusion criteria were congenital adrenal hyperplasia, exogenous glucocorticoid use, absence of unenhanced Hounsfield unit measurements (HU), and lack of established reference standard (histopathology, imaging characteristics, 2-year imaging follow up, or 5-year clinical follow up). Measures and Outcomes: measurements included 11-deoxycortisol, 17OH-progesterone, and 17OH-pregnenolone by liquid chromatography–mass spectrometry. Localized Generalized Matrix Learning Vector Quantization (LGMLVQ) analysis was used to develop serum steroid score and assessed with area under receiver operating curve (AUROC). Results: Of 263 patients with adrenal masses, 44 (17%) were diagnosed with ACC, 161 (61%) with adrenocortical adenomas (ACAs), 27 (10%) with other adrenal malignancies, and 31 (12%) with other. HU ≥ 20 were demonstrated in all ACCs, in all but one other adrenal malignancy, and only in 58 (31%) ACAs. All 3 steroids were higher in patients with ACCs vs nonACCs, including when comparing ACCs with functioning ACAs, and with ACAs with HU ≥ 20 (P<0.0001 for all). LGMLVQ analysis yielded a serum steroid score that discriminated between ACC and non-ACC groups with a mean threshold fixed AUROC of 0.823. Serum steroid score of 0.29 demonstrated a mean false negative rate of 0% and a score of 0.61 demonstrated a mean false positive rate of 0%. Conclusions: We showed that measurements of 11-deoxycortisol, 17OH-progesterone, and 17OH-pregnenolone could be valuable in diagnosing ACC. After appropriate validation, serum steroid score could be integrated in clinical practice. Presentation: 6/2/2024

Abstract Background We took advantage of our verification of a new biotin-resistant 25-hydroxyvitamin D (vitamin D) immunoassay formulation to compare analytical performance of the outgoing formulation and assays from Roche, Diasorin and Beckman. Liquid chromatography with tandem mass spectrometry (LCMS) was an independent arbiter of vitamin D concentration and provided quantification of vitamin D2 and vitamin D3. Methods Twenty-five specimens from patients on high-dose vitamin D2 supplementation (50 000 IU/week) and fifty additional specimens spanning our measurable range were identified by the Dartmouth Hitchcock Analytics Institute. Aliquots were tested by the Roche cobas Vitamin D Total II and Vitamin D Total III assays, deidentified, split, and shipped to other study sites for measurement by LCMS, the Diasorin Liaison 25 OH Vitamin D Total assay, and the Beckman Coulter Access 25(OH) Vitamin D Total assay. Estimated vitamin D2 was calculated by subtracting the LCMS-measured vitamin D3 result from the immunoassay total vitamin D result. Bias calculations assume LCMS measurements as the true concentration. Statistical analyses were performed in R. This study was approved by the Dartmouth Hitchcock Medical Center Institutional Review Board. Results No significant differences were observed between platforms in absolute or relative bias in total vitamin D or estimated vitamin D2. Clinical classification was unanimous in 62/75 specimens. For thirteen specimens in which at least one disagreement was observed, immunoassay results for discrepant classification were no more than 10.2 ng/mL from the classification cutoff (median 2 ng/mL). Two specimens with 68 and 70 ng/mL vitamin D were classified as toxic (>100 ng/mL) by one immunoassay each. Conclusion Current vitamin D immunoassays continue to improve over their predecessors and offer good agreement across platforms. Vitamin D2 recovery no longer represents a clinically-concerning obstacle. These immunoassays display positive bias for total vitamin D relative to LCMS but generally result in correct clinical classification.