Singh, Ravinder Jit

Abstract Disclosure: A.M. Gonzalez Gil: None. E.F. Elli: None. R.J. Singh: None. S. Peres: None. A.Y. Chang: None. Background: Treatment of hypercortisolism in primary bilateral macronodular adrenal hyperplasia (PBMAH) with mild autonomous cortisol secretion (MACS) can be challenging. Medical treatment is useful for therapeutic purposes and as a bridge for adrenalectomy. We present the case of a patient who benefited from mifepristone but developed hyperestrogenism. Clinical Case: A 64-year-old man with prediabetes, hypertension, and cardiovascular disease had incidentally discovered bilateral nodular adrenal enlargement on CT scan following coronary artery bypass surgery. A few months later, he reported increasing fatigue, brain fog, weight gain, and worsening blood pressure. Physical exam showed no features of hypercortisolism. Work-up revealed baseline AM cortisol 17.3 mcg/dL [reference range (RR) 4.8-20], ACTH 10 pg/mL (RR 7.2-63) and DHEA-S 55 mcg/dL (RR 12-227); two abnormal AM cortisols after 1 mg overnight dexamethasone (5.4 and 6.9 mcg/dL; cut-off <1.8), and a normal 24-hour urine free cortisol (23 mcg/24h, RR 3.5-45). 24-hour urine metanephrines and aldosterone/renin ratio were normal. A 2-hour 75 g oral glucose tolerance test was diagnostic for type 2 diabetes mellitus (2-hour glucose 214 mg/dL). Baseline total testosterone (TT) was 366 ng/dL (RR 264-916) with normal follicle stimulating hormone (FSH) and luteinizing hormone (LH)concentrations. After a diagnosis of MACS, adrenal vein sampling showed bilateral excess cortisol secretion (lateralization ratio 1.09). Medical management versus right adrenalectomy based on nodule burden were offered, and he started mifepristone. With initial symptom improvement, his dose was increased from 300 mg to 300 mg alternating with 600 mg daily. When he developed increased blood pressure and hypokalemia, eplerenone was added. After 6 months of mifepristone and 5 months eplerenone 50 mg daily, he developed tender gynecomastia with elevated estradiol (106 pg/mL, RR ≤39), low TT (112 ng/dL) and undetectable FSH and LH. As expected with mifepristone, 17-hydroxyprogesterone was high (933 ng/dL, RR 51-190), but androstenedione and DHEA-S were normal. Reduction in mifepristone and eplerenone decreased estradiol levels (56 pg/mL) but gonadotrophins remained undetectable and TT decreased to 72 ng/dL. Despite discontinuation of eplerenone for 1 month, estradiol again increased (91 pg/mL), TT remained low (77 ng/dL), and mastalgia persisted. A decision to stop mifepristone and proceed with right adrenalectomy was made. Conclusion: This is a previously unreported incident of symptomatic estradiol-induced secondary hypogonadism on mifepristone therapy. Hyperestrogenism with gynecomastia and secondary hypogonadism with mifepristone suggests that some individuals may convert cortisol precursors to estradiol. Presentation: Saturday, July 12, 2025

Objectives Chronic pancreatitis (CP) is a chronic fibroinflammatory condition of the pancreas difficult to diagnose in early stages. Novel biomarkers useful to facilitate early diagnosis or treatment responses may be found in biofluids. Although saliva can be easily and noninvasively collected from patients, useful salivary biomarkers from CP patients have not yet been identified. Methods Here, we analyzed the proteome by quantitative proteomics, cytokine/chemokine levels by Luminex analysis, prostaglandin E2 (PGE2) levels by a mass spectrometry-based assay, and bacterial species diversity by 16S ribosomal ribonucleic acid sequencing in saliva samples from confirmed CP patients and healthy controls. Results Our results indicate the presence of various differentially expressed proteins, cytokines/chemokines, and a loss of oral bacterial diversity in the saliva of CP patients. The PGE2 levels trend toward elevation in CP patients. Area under the receiver operating characteristic curve models for proteomic, cytokine, and PGE2 assays ranged from 0.59 to 0.90. Conclusions Collectively, our studies identify a range of putative CP biomarkers and alterations in human saliva requiring further validation. The biomarker discovery approaches we used might lead to identification of biomarkers useful for CP diagnosis and monitoring.

Abstract Context The normal cortisol response 30 or 60 minutes after cosyntropin (ACTH[1–24]) is considered to be ≥18 μg/dL (500 nmol/L). This threshold is based on older serum cortisol assays. Specific monoclonal antibody immunoassays or LC-MS/MS may have lower thresholds for a normal response. Objective To calculate serum cortisol cutoff values for adrenocorticotropic hormone (ACTH) stimulation testing with newer specific cortisol assays. Methods Retrospective analysis of ACTH stimulation tests performed in ambulatory and hospitalized patients suspected of adrenal insufficiency (AI). Serum samples were assayed for cortisol in parallel using Elecsys I and Elecsys II immunoassays, and when volume was available, by Access immunoassay and LC-MS/MS. Results A total of 110 patients were evaluated. Using 18 μg/dL as the cortisol cutoff after ACTH stimulation, 14.5%, 29%, 22.4%, and 32% of patients had a biochemical diagnosis of AI using the Elecsys I, Elecsys II, Access, and LC-MS/MS assays, respectively. Deming regressions of serum cortisol were used to calculate new cortisol cutoffs based on the Elecsys I cutoff of 18 μg/dL. For 30-minute values, new cutoffs were 14.6 μg/dL for Elecsys II, 14.8 μg/dL for Access, and 14.5 μg/dL for LC-MS/MS. Baseline cortisol <2 μg/dL was predictive of subnormal stimulated cortisol values. Conclusion To reduce false positive ACTH stimulation testing, we recommend a new serum cortisol cutoff of 14 to 15 μg/dL depending on the assay used (instead of the historical value of 18 μg/dL with older polyclonal antibody assays). Clinicians should be aware of the new cutoffs for the assays available to them when evaluating patients for AI.