Citations

AbstractObjectiveAdrenal schwannomas and juxta‐adrenal schwannomas are rare tumours. We aimed to summarise their clinical, biochemical and imaging characteristics.DesignSingle‐centre retrospective study of eligible patients between 1995 and 2022.Patients and MeasurementsPatients with a histopathologic diagnosis of adrenal or juxta‐adrenal schwannoma.ResultsTwenty‐four patients were diagnosed with either primary adrenal schwannoma (8, 33%) or juxta‐adrenal schwannoma (16, 67%). Most tumours (21, 88%) were discovered incidentally on imaging. All tumours were unilateral, with 15 (62%) on the left and 9 (38%) on the right. At diagnosis, the median tumour 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 = .037). On imaging, the tumours 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%). The median unenhanced computed tomography attenuation was 30 Hounsfield units (HU) (range, 12–38 HU). Of the 20 patients who underwent complete hormonal testing, all had nonfunctioning tumours. There was no recurrence or new tumour development in our cohort.ConclusionsAdrenal and juxta‐adrenal schwannomas are nonfunctioning benign tumours that present with indeterminate radiographic features, including large tumour size and increased unenhanced CT attenuation. We did not find an imaging phenotype that was diagnostic of schwannoma. The diagnosis of this rare tumour is based on biopsy or resection.

AbstractWhile most benign lesions of the adrenal glands represent either an adrenocortical adenoma or a myelolipoma, the advent and frequent use of high-resolution radiological investigations have led to relatively increased incidental discovery of rare adrenal lesions, specifically benign adrenal cysts, adrenal ganglioneuromas, adrenal schwannomas, adrenal hemorrhage, and adrenal calcifications. Radiological characteristics of the different rare benign adrenal lesions could vary from distinct to indeterminate. Though typically nonfunctional, these rare lesions require evaluation for adrenal hormone excess, as they may phenotypically appear similar to pheochromocytoma or adrenocortical carcinoma and could sometimes be associated with or conceal an underlying functional adrenal tumor. In this review, we discuss the various rare benign adrenal lesions, emphasizing a practical perspective.

AbstractBackgroundAdrenal metastasis is the most common adrenal malignancy and can be bilateral in up to 43% of patients. Radiotherapy (RT) is one option available to treat adrenal metastases. The risk of primary adrenal insufficiency (PAI) after adrenal RT is unclear.ObjectiveDetermine the incidence and the timeline of PAI in patients undergoing adrenal RT.Design, Setting and ParticipantsSingle‐centre longitudinal retrospective cohort study of adult patients with adrenal metastases treated with RT between 2010 and 2021.ResultsOf 56 patients with adrenal metastases treated with adrenal RT, eight (14.3%) patients developed PAI at a median of 6.1 months (interquartile range [IQR]: 3.9–13.8) after RT All patients developing PAI had either unilateral RT in the setting of contralateral adrenalectomy or bilateral adrenal RT. Patients who developed PAI received a median RT dose of 50 Gy (IQR: 44–50 Gy), administered in a median of five fractions (IQR: 5–6). Treated metastases decreased in size and/or metabolic activity on positron emission tomography in seven patients (87.5%). Patients were initiated on hydrocortisone (median daily dose of 20 mg, IQR: 18–40) and fludrocortisone (median daily dose of 0.05 mg, IQR: 0.05–0.05 mg). At the end of the study period, five patients died, all due to extra‐adrenal malignancy, at a median time of 19.7 months (IQR: 16–21.1 months) since RT and median time of 7.7 months (IQR: 2.9–12.5 months) since the diagnosis of PAI.ConclusionPatients receiving unilateral adrenal RT with two intact adrenal glands have a low risk of PAI. Patients receiving bilateral adrenal RT have a high risk of PAI and require close monitoring.

Abstract Objective 11-oxygenated androgens significantly contribute to the circulating androgen pool. Understanding the physiological variation of 11-oxygenated androgens and their determinants is essential for clinical interpretation, for example, in androgen excess conditions. We quantified classic and 11-oxygenated androgens in serum and saliva across the adult age and body mass index (BMI) range, also analyzing diurnal and menstrual cycle-dependent variation. Design Cross-sectional. Morning serum samples were collected from 290 healthy volunteers (125 men, 22-95 years; 165 women, 21-91 years). Morning saliva samples were collected by a sub-group (51 women and 32 men). Diurnal saliva profiles were collected by 13 men. Twelve women collected diurnal saliva profiles and morning saliva samples on 7 consecutive days during both follicular and luteal menstrual cycle phases. Methods Serum and salivary steroids were quantified by liquid chromatography–tandem mass spectrometry profiling assays. Results Serum classic androgens decreased with age-adjusted BMI, for example, %change kg/m2 for 5α-dihydrotestosterone: men −5.54% (95% confidence interval (CI) −8.10 to −2.98) and women −1.62% (95%CI −3.16 to −0.08). By contrast, 11-oxygenated androgens increased with BMI, for example, %change kg/m2 for 11-ketotestosterone: men 3.05% (95%CI 0.08-6.03) and women 1.68% (95%CI −0.44 to 3.79). Conversely, classic androgens decreased with age in both men and women, while 11-oxygenated androgens did not. Salivary androgens showed a diurnal pattern in men and in the follicular phase in women; in the luteal phase, only 11-oxygenated androgens showed diurnal variation. Conclusions Classic androgens decrease while active 11-oxygenated androgens increase with increasing BMI, pointing toward the importance of adipose tissue mass for the activation of 11-oxygenated androgens. Classic but not 11-oxygenated androgens decline with age.

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.