Bancos, Irina

Abstract Context Patients with adrenal hormone excess demonstrate increased cardiovascular (CV) risk and mortality. Objective We aimed to determine the effect of adrenal disorders on the inflammation marker glycoprotein acetylation (GlycA), total branched-chain amino acids (BCAAs), ketone bodies, and the gut microbiome-derived metabolites trimethylamine N-oxide (TMAO) and betaine. Methods We conducted a single-center cross-sectional study of patients with nonfunctioning adenomas (NFAs), mild autonomous cortisol secretion (MACS), primary aldosteronism (PA), Cushing syndrome (CS), pheochromocytoma/paragangliomas (PPGLs), other benign or malignant adrenal masses, and adrenocortical carcinoma (ACC) between January 2015 and July 2022 (n = 802). Referent individuals included participants in the PREVEND (Prevention of Renal and Vascular End-Stage Disease) study (n = 5241). GlycA, BCAAs, ketone bodies, TMAO, and betaine were measured using nuclear magnetic resonance spectroscopy. Multivariable logistic analyses were adjusted for age, sex, body mass index, smoking, hypertension, diabetes mellitus, and statin therapy. Results In age- and sex-adjusted comparison to referent individuals, increased GlycA was noted in all patient categories, increased BCAAs in NFA, MACS, CS, PA, and ACC, increased TMAO in patients with other malignant adrenal masses, increased betaine in NFA and MACS, and increased ketone bodies in NFA, CS, and ACC. Essentially similar findings were observed in fully adjusted analysis and after exclusion of participants with diabetes and CV disease. Conclusion Patients with functioning and nonfunctioning adrenal masses demonstrated increased GlycA and BCAAs, biomarkers associated with adverse cardiometabolic disorders and mortality. Patients with NFA demonstrated an adverse metabolic profile similar to patients with MACS and CS.

Abstract Glucocorticoids are widely prescribed as anti-inflammatory and immunosuppressive agents. This results in at least 1% of the population using chronic glucocorticoid therapy, being at risk for glucocorticoid-induced adrenal insufficiency. This risk is dependent on the dose, duration and potency of the glucocorticoid, route of administration, and individual susceptibility. Once glucocorticoid-induced adrenal insufficiency develops or is suspected, it necessitates careful education and management of affected patients. Tapering glucocorticoids can be challenging when symptoms of glucocorticoid withdrawal develop, which overlap with those of adrenal insufficiency. In general, tapering of glucocorticoids can be more rapidly within a supraphysiological range, followed by a slower taper when on physiological glucocorticoid dosing. The degree and persistence of HPA axis suppression after cessation of glucocorticoid therapy are dependent on overall exposure and recovery of adrenal function varies greatly amongst individuals. This first European Society of Endocrinology/Endocrine Society joint clinical practice guideline provides guidance on this clinically relevant condition to aid clinicians involved in the care of patients on chronic glucocorticoid therapy.

Abstract Context Patients with nonfunctioning adrenal adenomas (NFA) and mild autonomous cortisol secretion (MACS) demonstrate an increased risk of chronic kidney disease (CKD); however, factors associated with CKD are unknown. Objective We aimed to identify the factors associated with CKD and assess the effect of adrenalectomy on kidney function in patients with NFA or MACS. Methods A single-center cohort study of patients with NFA and MACS, 1999 to 2020, was conducted. MACS was diagnosed based on post dexamethasone suppression test (DST) cortisol greater than or equal to 1.8 mcg/dL. Age, sex, dysglycemia, hypertension, therapy with statin, angiotensin-converting enzyme inhibitor, or angiotensin II receptor blocker were included in the multivariable analysis. Outcomes included estimated glomerular filtration rate (eGFR) at the time of diagnosis with MACS or NFA and postadrenalectomy delta eGFR. Results Of 972 patients, 429 (44%) had MACS and 543 (56%) had NFA. At the time of diagnosis, patients with MACS had lower eGFR (median 79.6 vs 83.8 mL/min/1.73 m2; P < .001) than patients with NFA. In a multivariable analysis, factors associated with lower eGFR were older age, hypertension, and higher DST. In 204 patients (MACS: 155, 76% and NFA: 49, 24%) treated with adrenalectomy, postadrenalectomy eGFR improved in both groups starting at 18 months up to 3.5 years of follow-up. Factors associated with increased eGFR were younger age, lower preadrenalectomy eGFR, and longer follow-up period. Conclusion DST cortisol is an independent risk factor for lower eGFR in patients with adrenal adenomas. Patients with both MACS and NFA demonstrate an increase in eGFR post adrenalectomy, especially younger patients with lower eGFR pre adrenalectomy.

Abstract Estrogen-secreting adrenocortical carcinoma (ACC) is exceedingly rare, representing 1% to 2% of all ACCs. We present a case of a 65-year-old man diagnosed with an estrogen-secreting, 4.3-cm right adrenal mass discovered during work-up for bilateral gynecomastia. Gynecomastia and hyperestrogenism resolved after laparoscopic adrenalectomy, and pathology was reported as adrenocortical adenoma. However, 5 years later, he again developed bilateral gynecomastia because of recurrent hyperestrogenism. Imaging revealed multiple metastases in the abdomen. Urine steroid profiling demonstrated increased androgen precursors, androgen metabolites, and glucocorticoid precursors. Ultrasound-guided biopsy of one of the metastases confirmed ACC. Initial therapy included debulking surgery with removal of metastatic lesions. Mitotane therapy was initiated 4 weeks later along with hydrocortisone for anticipated mitotane-induced adrenal insufficiency. Histopathology from the adrenalectomy specimen 5 years earlier was rereviewed and confirmed ACC. Estrogen-secreting adrenal tumors are exceedingly rare, and the majority are malignant. This case underlines the importance of making an initial accurate diagnosis of adrenal malignancy that allows better surgical planning and appropriate monitoring. Indeterminate imaging characteristics of the adrenal mass, as well as the presentation with estrogen excess, suggested an elevated risk for ACC. Initial pathology-based misdiagnosis illustrates the need for an expert adrenal pathologist to review these rare tumors.

Abstract Objective Overnight metyrapone test (OMT) is a dynamic test used to diagnose secondary adrenal insufficiency (SAI). Data on OMT use and its safety are scarce. We aimed to describe the indications and safety of outpatient OMT and compare OMT to the cosyntropin stimulation test (CST). Design Single‐centre retrospective study of adult patients undergoing OMT between 1 April 2018 and 27 January 2023. Measurements OMT‐related adverse events, post‐OMT diagnosis of SAI, and OMT comparison to CST. Results OMT was performed in 114 patients (81, 71% women) at a median age of 48 (interquartile range 37–58). The pretest probability for SAI was low in 52 (46%) patients, moderate in 48 (42%) patients and high in 14 (12%) patients. Adverse events were reported in 7 (6.1%) patients and were mild except for one hospitalization. No baseline or OMT‐related factors were associated with the development of adverse events. Prevalence of the OMT‐based SAI diagnosis was 26 (23%) and 47 (46%) using 11‐deoxycortisol cutoff <7 and <10 mcg/dL, respectively. Higher pretest probability was associated with the OMT‐based diagnosis of SAI. Post‐OMT 11‐deoxycortisol cutoff of 10 mcg/dL was used most to diagnose SAI. Compared to the OMT‐based diagnosis of SAI (11‐deoxycortisol cutoff of 10 mcg/dL), the specificity of CST was 100%, but the sensitivity was only 52%. Conclusions OMT was well tolerated and used in patients with low and moderate pretest probability for SAI. CST can erroneously exclude patients with SAI. Thus, OMT should be considered in selected patients with normal CST.

Abstract Disclosure: S.A. Jacob: None. M. Itani: None. M.J. Hoegger: None. D. Ludwig: None. T. Pandian: None. T.C. Brown: None. L.M. Brunt: None. I. Bancos: None. N. Genere: None. Introduction: Adrenal mass incidence has increased tenfold over the last two decades, with most masses detected in individuals over 40 years of age. The majority of these adrenal masses are benign (&gt;80%), and few are malignant (8%) or hormonally active (4%); most are incidentally detected. Studies suggest higher rates of hormonally active and malignant adrenal masses in younger patients, however, evidence for this age group is scarce. In two recent large cohort studies of adrenal masses, young adults (18-40 years) represented only 0.2-7.1% of individuals studied. This study aimed to characterize clinical, imaging, and biochemical presentation of young adults diagnosed with adrenal masses. Methods: This is a retrospective cohort study of young adults (18-40 years) with adrenal masses detected based on a radiology report text database search between January 2015 and December 2021 at a tertiary medical center. Exclusion criteria included pre-existing adrenal masses before 2015, hyperplasia, or masses &lt;1cm. Images were reviewed by abdominal radiologists, and clinical data were obtained through review of electronic medical records. Results: A total of 255 young adults (56% women, 61% white) were diagnosed with adrenal masses with median age 35 (IQR 30-39) years. Genetic predisposition syndrome was present in 6%. Comorbidities included: BMI &gt;30 kg/m2 in 48%, hypertension in 35%, and diabetes in 10%. Adrenal masses were detected incidentally in 72% and during cancer staging in 16%. Median mass size was 1.9cm (IQR 1.4-2.7cm) and 49% (39/79) were lipid poor (Hounsfield units &gt;10). Only 22% of patients underwent hormonal evaluation. Final diagnoses included 16% malignancy, 9% benign adenoma with overt hormone excess, 40% benign adenoma with incomplete hormonal evaluation and 24% radiographically indeterminate masses. Subgroup analysis showed that adrenal masses in those &lt;30 years old compared to 31-40 year-olds were more frequently associated with tumor predisposition syndrome (15% vs 3%, p&lt;0.01) and more often lipid poor (76% vs 40%, p&lt;0.01); but, no differences in frequency of malignancy or overt hormone excess were identified. Discussion: We found a higher frequency of malignancy and overt hormonal excess in our cohort of young adults compared to previously published studies, though direct comparisons are limited by differences in methodology. These findings, in addition to high frequencies of metabolic disease in our cohort, would suggest the need for hormonal assessment in young adults; yet, this was completed in only a minority of patients. Additional areas of research may include studying hormonal status of adrenal masses in young adults in a multi-center cohort to overcome issues of selection bias and increase the rates of those with complete hormonal evaluation. Presentation: Thursday, June 15, 2023

Abstract Disclosure: S. Paknikar: None. J. McHugh: None. K. Rachmasari: None. I. Bancos: None. Introduction: Ectopic secretion of adrenocorticotropic hormone (ACTH) is a rare and severe form of Cushing Syndrome (CS) that requires an urgent specialized approach for diagnosis and management. Clinical Case: A 50-year-old woman was referred to endocrinology due to concern for CS. Over the previous year she had developed progressive weakness, edema, weight gain with abdominal fat redistribution, hypertension, and multiple compression fractures. On exam, she had a profound proximal myopathy, reported 10/10 pain along the spine, and was hypertensive (170/105 mm Hg) with normal other vitals. The patient's sodium was 141mmol/L [reference range 135-145 mmol/ L], potassium 4.1 mmol/L [3.6-5.2 mmol/L] while on spironolactone, and creatinine was 0.57 mg/dL [0.59-1.04 mg/dL]. Due to the severity of her symptoms, she was admitted to the hospital. Hormonal work up was consistent with an ACTH dependent CS: ACTH was 121pg/mL [7.2-63 pg/mL] and 24-hour urine cortisol was 645 mcg/24 hr [3.5-45 mcg/24 hr]. Workup for ACTH secreting tumor included a pituitary MRI which showed a 3 mm area of delayed enhancement in the pituitary gland, felt to be artifactual. A chest computed tomography (CT) showed a 1.3 cm low-density nodule in the right upper lobe concerning for a neuroendocrine tumor. A Gallium-68 DOTATATE Positron emission tomography/CT scan was performed and demonstrated that the nodule was highly DOTATATE avid (Krenning score of 3, scale of 0-4). These findings supported a diagnosis of ectopic CS caused by an ACTH secreting lung neuroendocrine tumor. Management of ectopic CS was twofold: addressing the underlying ACTH secreting lesion and urgent treatment of hypercortisolism and its consequences. In this case, this was achieved with CT-guided cryoablation of the right upper lobe nodule. The ACTH levels were monitored postoperatively, and when decreased (9.3pg/mL [ 7.2-63 pg/mL], glucocorticoid replacement therapy was initiated. As a result of prolonged hypercortisolism, the patient experienced multiple compression fractures and debility. Physical therapy was recommended for recovery from the compression fractures as well as proximal myopathy. Enoxaparin was initiated due to risk of venous thromboembolism from CS. From an osteoporosis standpoint, she was continued on calcium and vitamin-D supplementation and treated with weekly alendronate. Her hypertension improved allowing medication reduction. Postoperatively, she received education on adrenal insufficiency and biochemical monitoring for adrenal insufficiency recovery was implemented. Conclusion: Ectopic ACTH secreting tumors represent a rare cause of CS and effective management requires consideration of medical comorbidities to determine the approach: surgical, cryoablative, or medical therapy alone, mitigation of Cushing syndrome sequelae, and prompt recognition and treatment of glucocorticoid withdrawal. Presentation: Thursday, June 15, 2023