Bancos, Irina

Primary aldosteronism (PA) is the most common cause of secondary hypertension but is frequently underrecognized and undertreated. Patients with PA are at a markedly increased risk for target organ damage to the heart and kidneys. While patients with unilateral PA can be treated surgically, many patients with PA are not eligible or willing to undergo surgery. Steroidal mineralocorticoid receptor antagonists (MRAs) are highly effective for treating PA and reducing the risk of target organ damage. However, steroidal MRAs are often underprescribed and can be poorly tolerated by some patients due to side effects. Nonsteroidal MRAs reduce adverse renal and cardiovascular outcomes among patients with diabetic kidney disease and are bettertolerated than steroidal MRAs. While their blood pressure–lowering effects remain unclear, these agents may have a potential role in reducing target organ damage in patients with PA.

Received June 8, 2022; accepted October 11, 2022 Background Recent advances in omics techniques have allowed detailed genetic characterization of cortisol-producing adrenal adenoma (CPA). In contrast, the pathophysiology of CPAs has not been elucidated in detail on the level of tumor metabolic alterations. Methods The current study conducted a comprehensive mass spectrometry imaging (MSI) map of CPAs in relation to clinical phenotypes and immunohistochemical profiles of steroidogenic enzymes. The study cohort comprised 46 patients with adrenal tumors including CPAs (n 35) and nonfunctional adenomas (n 11). Results Severity of cortisol hypersecretion was significantly correlated with 29 metabolites (adjusted P 0.05). Adrenal androgens derived from the classic androgen pathway were inversely correlated with both cortisol secretion (rs 0.41, adjusted P 0.035) and CYP11B1 expression (rs 0.77, adjusted P 2.00E-08). The extent of cortisol excess and tumor CYP11B1 expression further correlated with serotonin (rs 0.48 and 0.62, adjusted P 0.008 and 2.41E-05). Tumor size was found to be correlated with abundance of 13 fatty acids (adjusted P 0.05) and negatively associated with 9 polyunsaturated fatty acids including phosphatidic acid 38:8 (rs 0.56, adjusted P 0.009). Conclusions MSI reveals novel metabolic links between endocrine function and tumorigenesis, which will further support the understanding of CPA pathophysiology.

Abstract Background Patients taking chronic opioids are at high risk of opioid induced adrenal insufficiency (OIAI). Previously, we showed that the prevalence of OIAI was 9% based on low morning cortisol, corticotropin (ACTH), and dehydroepiandrosterone sulfate (DHEAS). Data on the overnight metyrapone test to diagnose OIAI are sparse. We aimed to determine the prevalence of OIAI using overnight metyrapone test and identify changes in the steroid metabolome of patients treated with opioids. Methods Cross-sectional study of adult patients treated with opioid therapy of at least 20 morphine milligram equivalents (MME)/day for at least 3 months. Measurements included ACTH, cortisol, and DHEAS. Overnight metyrapone test was administered in all patients, and 24h urine steroid profiling was optional (25 steroids measured by liquid chromatography mass spectrometry1). All patients completed the quality-of-life survey (AddiQoL). Prevalence of OIAI was defined as sum of post-metyrapone 11-deoxycortisol and cortisol of <15 mcg/dL. Result: In 22 patients (median age 59 years [range, 38-74], 9, 41% women), median MME was 33 (20-161) mg, and median cumulative opioid exposure was 245 (10-2550) mg*years. Following the overnight metyrapone test, 7 (32%) patients were diagnosed with OIAI. Patients with OIAI had lower DHEAS concentrations (median of 21 mcg/dL[ 5-113] vs 54 [22-173], p =0. 03), but not cortisol (median 10[5.3-16] mcg/dL vs 13[5.3-22], p=0. 06) or ACTH (median 27[8.1-51] pg/mL vs 26[5.9-55], p=0.8). Patients with OIAI were treated with higher daily MME (100 mg[30-150] vs 30[20-161], p=0. 03) and had a higher cumulative exposure to opioids (median, 660 mg*years [250-2250] vs 150 [10-1288], p =0. 01). AddiQol scores were similar between groups (median of 68[56-84] vs 73[48-83], p= 0.97). Urine steroid profiling was performed in 18 patients. Patients with OIAI demonstrated 4 times lower total urine glucocorticoids (16334 mcg/24h vs 4377 mcg/24h, p=0. 003), all <10% of the reference range, and 3 times lower total urinary androgens (median of 805 mcg/24h vs 2320 mcg/24h, p=0.14). Conclusion Prevalence of OIAI using overnight metyrapone test is high at 32%. Patients diagnosed with OIAI were treated with higher doses of MME/day and had a higher cumulative exposure to opioids when compared to those without OIAI. Applying 24h urine steroid profiling we showed that total glucocorticoids are 4 times lower in those with OIAI (and all <10% of reference ranges) as opposed to those without OIAI. We showed that baseline measurements of ACTH, DHEAS, and cortisol may incorrectly exclude OIAI, and a dynamic test, such as overnight metyrapone test is needed when suspicion for OIAI is high. | 1. Hines JM, Bancos I, Bancos C, et al. High-Resolution, Accurate-Mass (HRAM) Mass Spectrometry Urine Steroid Profiling in the Diagnosis of Adrenal Disorders. Clin Chem. 2017;63(12): 1824-1835. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

Abstract Objectives Adrenal schwannomas and juxta-adrenal schwannomas are rare tumors with limited data on clinical and radiologic features. We aimed to summarize the clinical, biochemical, and imaging characteristics of adrenal and juxta-adrenal schwannomas. Methods We performed a single-center retrospective study of patients with a histopathologic diagnosis of adrenal or juxta-adrenal schwannoma between 1995-2022. Results A total of 24 patients (18, 75% women) were diagnosed with either primary adrenal schwannoma (8, 33%) or a juxta-adrenal schwannoma (16, 67%) at a median age of 57 years (range, 27 - 77 years). Most tumors (21, 88%) were discovered incidentally on imaging, while 2 were diagnosed because of symptoms of mass effect, and 1 diagnosed incidentally on pathology during nephrectomy performed for renal cell carcinoma. None of the patients had a known genetic syndrome. The median time from identification of schwannoma on imaging to hormonal evaluation was 62 days (range, 0–2076 days). All tumors were unilateral, with 15 (62%) on the left and 9 (38%) on the right. At diagnosis, the median tumor size was 4 cm (range, 2 - 13 cm). Adrenal schwannomas were smaller when compared to juxta-adrenal schwannomas (median of 3.1 cm [range, 2 - 9 cm] vs 4.6 cm [range, 2.3 - 13.3 cm]) (P=0. 037). On imaging, the tumors were round or oval in shape in 16 (70%), lobulated in 7 (30%), solid in 15 (68%), solid-cystic in 7 (32%), heterogeneous in 14 (61%), and homogeneous in 9 (39%). Scattered or peripheral calcifications were seen in 2 cases. In 9 patients with available contrast-enhanced CT, all of the schwannomas demonstrated enhancement. The median unenhanced CT attenuation was 30 Hounsfield units (HU) (range, 12 - 38 HU). In 6 patients with available follow-up imaging of at least 6 months, median growth per year was 0.27 cm (range, 0 - 0.8 cm). Of the 20 patients who underwent complete hormonal testing, all had non-functioning tumors. Biopsy was performed in 5 (20%) patients and all were diagnostic of schwannoma. Adrenalectomy was performed in in 23 (96%) patients (laparoscopic in 16 [70%] and open in 7 [30%]). Open adrenalectomy was more common in patients with larger tumors (median size 7.5 cm; range, 2–13.3 cm) when compared to patients treated laparoscopically (median size 4 cm; range, 2.3–5.4 cm) (P=0. 041). Postoperatively, patients were followed clinically for a median of 1.7 years (range, 0-19 years) or radiographically (n=11) for a median of 2 years (range, 0. 01-11 years), without recurrence or new tumor development. Conclusions Adrenal and juxta-adrenal schwannomas are nonfunctioning benign tumors that present with indeterminate radiographic features, including large tumor size and increased unenhanced CT attenuation. We did not find an imaging phenotype that was diagnostic of schwannoma. The diagnosis of this rare tumor is based on biopsy or resection. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

Abstract Introduction Limited data suggest low bone density in patients with adrenal adenomas. However, most studies are retrospective, single-center, and none were conducted in the United States. We aimed to determine the impact of cortisol and aldosterone excess on bone density. Methods We conducted a preliminary analysis of data from our multicenter, prospective observational study of adult patients with adrenocortical hormone excess and referent subjects without adrenal disorders (January 2019 - March 2022). Patients were diagnosed with non-functioning adenomas (NFA), adenomas with mild autonomous cortisol secretion, MACS (defined as cortisol following an overnight 1-mg dexamethasone suppression test (DST)>1.8 mcg/dL), adrenal or pituitary Cushing syndrome (CS), primary aldosteronism (PA), and concomitant PA-MACS. Referent subjects were patients undergoing cross-sectional imaging for reasons other than adrenal disease. All participants were interviewed about their bone health, and had bone density measurements at the spine, hips, and/or radius. Bone disease was defined as osteopenia (T-score -1.1 to -2.4), or osteoporosis (T-score < -2.5). Results A total of 417 participants included 156 referent subjects (88, 56% women, median age 65, range 2-95 years) and 261 patients (190, 73% women, median age 59, range 21-88 years). Patients were diagnosed with NFA (51, 19%), PA (46, 17%), MACS (122, 47%), PA-MACS (12, 5%), and CS (30,12%). When compared to referent subjects, sex- and age-adjusted analysis demonstrated an increased prevalence of bone disease only in patients with CS (OR 4.8, 95%CI 1.7-13), but not in other adrenal disorders. After excluding patients with CS, those with post-DST cortisol >5 mcg/dL demonstrated a higher prevalence of bone disease when compared to patients with post-DST cortisol between 1.8-5 mcg/dL (OR 2.8, 95%CI 1.2-6.5) and those with post-DST cortisol <1.8 mcg/dL (OR 2.7, 95% CI 1.1-6.7). Patients with MACS and post-DST cortisol between 1.8-5 mcg/dL did not demonstrate increased sex and age-adjusted prevalence of bone disease compared to those with post-DST <1.8 mcg/dL or referent subjects. However, using post-DST cortisol as a continuous variable, we found that after adjusting for sex and age, the risk of bone disease in patients increased by 13% (OR 1.13, 95%CI 1.6-1.2) for every 1 mcg/dL increase in post-DST cortisol. Conclusions The prevalence of osteopenia and osteoporosis increases proportional to the increase in post-DST cortisol concentrations. Patients with CS, and those with MACS and post-DST cortisol > 5mcg/dL have the highest prevalence of bone disease. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

AbstractObjectiveThe objective of this study was to evaluate the role of adrenal venous sampling (AVS) in guiding the management of patients with corticotropin (ACTH)‐independent glucocorticoid secretory autonomy and bilateral adrenal masses.Design and PatientsA cohort with 25 patients underwent AVS and surgical management.MeasurementsCortisol was measured from the adrenal veins (AVs) and inferior vena cava (IVC). AV/IVC cortisol ratio and cortisol lateralization ratio (CLR) (dominant AV cortisol concentration divided by the nondominant AV cortisol concentration) were calculated. Posthoc receiver‐operating characteristic curves were generated to determine the specificity of revised AV/IVC cortisol ratio and CLR in differentiating unilateral from bilateral disease.ResultsPatients underwent unilateral (n = 21) or bilateral (n = 4) adrenalectomy. The mean AV/IVC cortisol ratio for unilateral adrenalectomy was 12.1 ± 9.6 (dominant) and 4.7 ± 3.8 (contralateral) with a mean CLR of 3.6 ± 3.5. The mean AV/IVC cortisol ratio for bilateral adrenalectomy was 7.5 ± 2.1, with a mean CLR of 1.1 ± 0.6. At a mean follow‐up of 22 months, one patient who underwent unilateral adrenalectomy for the predicted bilateral disease developed recurrent mild autonomous cortisol secretion. Posthoc analyses demonstrated a specificity of 95%–100% for unilateral disease with AV/IVC cortisol ratio >9 for one side, <2.0 for the opposite side and a CLR > 2.3. The specificity was 80%–90% for bilateral disease with AV/IVC cortisol ratio >5.1 bilaterally and a CLR < 1.1.ConclusionsAmong patients with bilateral adrenal masses and ACTH‐independent autonomous cortisol secretion, AVS can distinguish between unilateral and bilateral disease with high specificity and may guide surgical management.

AbstractBackgroundBilateral idiopathic hyperaldosteronism (IHA) is responsible for 60% of primary aldosteronism (PA) cases. Medical management is standard of care for IHA. Unilateral adrenalectomy (UA) with the intent of debulking total aldosterone production as a palliative measure remains controversial.MethodsSingle‐center retrospective review (2010–2020) of patients undergoing UA with a diagnosis of PA due to IHA (lateralization index [LI] on adrenal venous sampling [AVS] < 4). Demographic, pre‐operative, intra‐operative, and post‐operative variables were assessed. Hypertensive regimens were converted to the WHO Defined Daily Dose (DDD).ResultsTwenty‐four patients were identified, 14, 58% male and mean age 52 ± 10 years. Preoperative hypokalemia was present in 22, 92% of patients. Median number of antihypertensives taken was 3 (interquartile range [IQR], 2–4) and median DDD was 4 (IQR, 3–5.3). Median lateralization index on AVS was 3.52 (range, 1.19–3.88). All operations were performed in minimally invasive fashion. There were no conversions to open procedure, ICU admissions, or post‐operative complications. Median follow‐up was 10.5 months (range, 1–145 months). Hypokalemia resolved in 17, 76% of patients at last follow‐up. Post‐operative median number of antihypertensives taken was 1 (IQR, 1–3) and median DDD was 2 (IQR, 0.5–2.75) from 4, P = 0.003. Three (%) patients required continuation of mineralocorticoid receptor antagonists post‐operatively. Blood pressure control improved in 65% of patients.ConclusionUnilateral adrenalectomy in the setting of bilateral hyperaldosteronism can improve blood pressure control and stabilize potassium levels in selected patients. Further prospective studies in larger cohorts will be necessary to further define the role of unilateral adrenalectomy in the setting of PA due to bilateral adrenal disease.

Abstract Objective Prolactinomas are treated with dopamine agonists (DAs) as first-line therapy and transsphenoidal surgery as an alternative approach for medically failed tumors. We sought to summarize the efficacy of stereotactic radiosurgery (SRS) in the medically and surgically failed prolactinomas as well as in nonsurgical candidates with medically failed prolactinomas by systematic review and meta-analysis. Method A literature search was conducted according to the Preferred Reporting Items for Systematic Review and Meta-Analyses guideline. Results A total of 11 articles (total N = 709) met inclusion criteria. Thirty-three percent of patients were able to achieve endocrine remission at a mean follow-up of 54.2 ± 42.2 months with no association between stopping DA and endocrine remission. Sixty-two percent of patients were able to achieve endocrine control with DA therapy and 34% of patients were able to decrease the dose of DA dose when compared with pre-SRS DA dose at the end of the follow-up period. However, 54% of patients required DA at the end of the follow-up to control hyperprolactinemia. Ninety percent of patients were able to achieve radiologic control at the end of the follow-up in comparison to pre-SRS imagings. Furthermore, 26% of patients newly developed hypopituitarism (one or more pituitary hormones) post-SRS throughout the follow-up period. Conclusion This systematic review and meta-analysis demonstrates SRS as an effective adjunct therapy in medically failed nonsurgical candidates or surgically and medically recalcitrant prolactinomas with a 33% chance of achieving endocrine remission, 62% of patients achieved hormonal control with DA and GKRS (gamma knife radio-surgery), with a 34% chance of decreasing DA dose and 90% chance of achieving radiologic control.

ImportanceAdrenalectomy is the definitive treatment for multiple adrenal abnormalities. Advances in technology and genomics and an improved understanding of adrenal pathophysiology have altered operative techniques and indications.ObjectiveTo develop evidence-based recommendations to enhance the appropriate, safe, and effective approaches to adrenalectomy.Evidence ReviewA multidisciplinary panel identified and investigated 7 categories of relevant clinical concern to practicing surgeons. Questions were structured in the framework Population, Intervention/Exposure, Comparison, and Outcome, and a guided review of medical literature from PubMed and/or Embase from 1980 to 2021 was performed. Recommendations were developed using Grading of Recommendations, Assessment, Development and Evaluation methodology and were discussed until consensus, and patient advocacy representation was included.FindingsPatients with an adrenal incidentaloma 1 cm or larger should undergo biochemical testing and further imaging characterization. Adrenal protocol computed tomography (CT) should be used to stratify malignancy risk and concern for pheochromocytoma. Routine scheduled follow-up of a nonfunctional adrenal nodule with benign imaging characteristics and unenhanced CT with Hounsfield units less than 10 is not suggested. When unilateral disease is present, laparoscopic adrenalectomy is recommended for patients with primary aldosteronism or autonomous cortisol secretion. Patients with clinical and radiographic findings consistent with adrenocortical carcinoma should be treated at high-volume multidisciplinary centers to optimize outcomes, including, when possible, a complete R0 resection without tumor disruption, which may require en bloc radical resection. Selective or nonselective α blockade can be used to safely prepare patients for surgical resection of paraganglioma/pheochromocytoma. Empirical perioperative glucocorticoid replacement therapy is indicated for patients with overt Cushing syndrome, but for patients with mild autonomous cortisol secretion, postoperative day 1 morning cortisol or cosyntropin stimulation testing can be used to determine the need for glucocorticoid replacement therapy. When patient and tumor variables are appropriate, we recommend minimally invasive adrenalectomy over open adrenalectomy because of improved perioperative morbidity. Minimally invasive adrenalectomy can be achieved either via a retroperitoneal or transperitoneal approach depending on surgeon expertise, as well as tumor and patient characteristics.Conclusions and RelevanceTwenty-six clinically relevant and evidence-based recommendations are provided to assist surgeons with perioperative adrenal care.