Dogra, Prerna

Abstract Disclosure: A. Kittithaworn: None. P. Dogra: None. L. Rahimi: None. R. Sandooja: None. I. Bancos: None. Background: Adrenal calcification is discovered incidentally on imaging performed for reasons other than adrenal pathology and represents <1% of benign adrenal lesions. Data on the etiology and morphology of adrenal calcifications are scarce. Objective: To determine the etiology and imaging characteristics of adrenal calcification. Methods: We conducted a single-center retrospective study of patients with adrenal calcification on abdominal computed tomography between January 1st,2017 and December 31st, 2021. Medical records were reviewed for demographics, discovery mode, etiology and morphology. Subgroup analysis of patients with calcification/s associated with an adrenal mass was performed. Results: Adrenal calcification was reported in 540 patients (245, 45% women, median age 65 years (IQR 54-74). Only a minority of patients with adrenal calcifications were evaluated by an endocrinologist (167, 31%). Adrenal calcifications were discovered incidentally in 472 (87%) patients, during cancer staging imaging in 66 (12%), and evaluation of other symptoms in 2 (<1%). The etiology of adrenal calcification was most commonly idiopathic (390, 72%), followed by adrenal mass (112, 21%), hemorrhage (20, 6%), and granulomatous disease (8, 1.5%). Adrenal calcifications were bilateral in 34 (6%) patients and unilateral in 506 (94%), with a similar left and right distribution. Unilateral calcifications were more frequently single (399, 79%) with punctate (60%), coarse (28%), linear/curvilinear (9%), or eggshell (3%) morphology. Bilateral adrenal calcifications presented more frequently with multiple lesions (53% vs 21% in unilateral calcifications, p <0.0001), and were coarse (59%), punctate (29%), or linear (9%). When associated with either unilateral or bilateral adrenal mass, calcifications were either central (50, 45%), peripheral (44, 39%), septal (10, 9%), or both central and peripheral (7, 7%) in relation to the adrenal mass. Adrenal masses associated with adrenal calcifications were: adrenal adenomas in 63 (56%), myelolipomas or cysts in 28 (23%), metastases in 12 (11%), adrenal carcinomas in 4 (4%), pheochromocytomas in 2 (2%), and other rare masses in 3 (3%) patients. Patients with adrenal calcifications associated with an adrenal mass were younger at the time of diagnosis (median of 63 vs 66 years, p=0.014), and had a higher proportion of women (61% vs. 41%, p=0.0002), and were more likely to be discovered during cancer staging imaging (21% vs. 10%, p=0.003). Adrenal mass-associated calcifications were more frequently multiple rather than single lesions (46% vs. 17%, p<0.0001). Conclusion: Adrenal calcifications are usually unilateral single punctate or coarse lesions of unclear etiology. The majority of the adrenal masses that demonstrated calcifications were benign, however adrenal malignancy or pheochromocytomas were diagnosed in 17% of cases. Presentation: Friday, June 16, 2023

Abstract Disclosure: L. Rahimi: None. A. Kittithaworn: None. R. Gregg Garcia: None. J. Saini: None. P. Dogra: None. E. Atkinson: None. S. Achenbach: None. A. Kattah: None. I. Bancos: None. Objective: Patients with mild autonomous cortisol secretion (MACS) have been reported to have a higher prevalence of chronic kidney disease (CKD), possibly due to the direct effect of hypercortisolism on kidney function and indirect effect of MACS-associated cardiovascular comorbidities, such as diabetes, hypertension, obesity, and dyslipidemia. Limited studies suggest improvement of kidney function following adrenalectomy in patients with MACS. In this study, we aimed to assess the factors associated and the degree and timing of change in kidney function post adrenalectomy in patients with MACS or nonfunctioning adrenal adenoma (NFA). Methods: We conducted a retrospective single-center study and included adult patients with MACS or NFA diagnosed based on a post-dexamethasone cortisol cutoff of 1.8 mcg/dL, who underwent adrenalectomy between 1999-2022. The change in estimated glomerular filtration rate (eGFR) before and up to 3.5 years after adrenalectomy was defined as the primary outcome. Demographics and comorbidities were included in univariable and multivariable analyses. Results: We included 155 (76.0%) patients with MACS and 49 (24.0%) patients with NFA treated with adrenalectomy. The proportion of women was high in both MACS and NFA (71.6% vs 69.4%, p=0.77), however, patients with MACS were older (median age 59.2 vs 54.6 years in NFA, p=0.05). The prevalence of hypertension was higher in MACS vs NFA (71.0% vs 53.1%, p=0.02), while the prevalence of diabetes (25.2% vs 28.6%, p=0.89), dyslipidemia (47.7% vs 46.9%, p=0.92), smoking (74.2% vs 68.9%, p=0.49) and obesity (median BMI 30.4 vs 31.8 kg/m2, p=0.35) was similar between the two groups. Prior to adrenalectomy, patients with MACS had lower eGFR (median 84.4 vs 89.2 ml/min/1.73m2, p=0.09) and a higher prevalence of CKD stage ≥ 3 (16.1% vs 8.2%, p= 0.16). In patients with MACS, after an initial decline of eGFR within 6 months post adrenalectomy (mean decrease 5.3 ml/min/1.73m2), eGFR increased by a mean of 4.9 points at 18-30 months, and by a mean of 8.1 points at 30-42 months post-adrenalectomy (p<0.01). Patients with NFA followed a similar eGFR change trend (p=NS). When comparing post-adrenalectomy delta eGFR in patients with MACS vs NFA, no significant differences were found. After adjusting for age, sex, pre-adrenalectomy eGFR, patient group, hypertension, antihypertensive therapy, and diabetes, there were still significant changes in eGFR over time. In a multivariable analysis, younger age (est -031, p<0.001) and lower pre-adrenalectomy eGFR (est-0.27, p=0.001) were associated with kidney function improvement post-adrenalectomy. Conclusion: Patients with MACS and NFA demonstrate improvement of eGFR over the 3.5 years of follow up post-adrenalectomy. The factors that are associated with improvement of eGFR are lower eGFR before surgery, younger age at time of adrenalectomy and longer follow up post adrenalectomy. Presentation: Friday, June 16, 2023

Abstract Objective Frailty, characterized by multi-system decline, increases vulnerability to adverse health outcomes and can be measured using Frailty Index (FI). We aimed to assess the prevalence of frailty in patients with adrenal disorders (based on hormonal sub-type) and examine association between FI and performance-based measures of physical function. Design Multi-centre, cross-sectional study (March 2019-August 2022). Methods Adult patients with adrenal disorders (non-functioning adrenal adenomas [NFA], mild autonomous cortisol secretion [MACS], Cushing syndrome [CS], primary aldosteronism [PA]) and referent subjects without adrenal disorders completed a questionnaire encompassing 47 health variables (comorbidities, symptoms, daily living activities). FI was calculated as the average score of all variables and frailty defined as FI ≥ 0.25. Physical function was assessed with hand grip, timed up-and-go test, chair rising test, 6-minute walk test, and gait speed. Results Compared to referent subjects (n = 89), patients with adrenal disorders (n = 520) showed increased age, sex, and body mass index-adjusted prevalence of frailty (CS [odds ratio—OR 19.2, 95% confidence interval—CI 6.7-70], MACS [OR 12.5, 95% CI 4.8-42.9], PA [OR 8.4, 95% CI 2.9-30.4], NFA [OR 4.5, 95% CI 1.7-15.9]). Prevalence of frailty was similar to referent subjects when post-dexamethasone cortisol was <28 nmol/L and was higher when post-dexamethasone cortisol was 28-50 nmol/L (OR 4.6, 95% CI 1.7-16.5). FI correlated with all measures of physical function (P < .001). Conclusions Whilst frailty prevalence was highest in patients with adrenocortical hormone excess, even patients with NFA demonstrated an increased prevalence compared to the referent population. Future longitudinal studies are needed to evaluate the impact of various management strategies on frailty.

Abstract Sparse data are available on the etiology, morphology, clinical presentation, and outcomes of adrenal calcification. In this single-center retrospective study of 540 consecutive patients (median age 65 years, 45% women) with adrenal calcification on computed tomography (December 2017 to January 2021), most were discovered incidentally (472, 87%). The commonest etiology was idiopathic (389, 72%), followed by the adrenal tumor (113, 21%), hemorrhage (29, 5%), and infiltrative disease (7, 1%). Calcified adrenal tumors were predominantly benign (92, 81%) and primarily adenomas (63, 69%), whereas the most common calcified adrenal malignancy (16, 18%) was metastasis (12, 67%). Calcification (unilateral 94%, bilateral 6%) morphology varied from punctate (313, 58%) to coarse (165, 30%), linear/curvilinear (46, 9%), and rim-like (16, 3%). In summary, adrenal calcifications are usually incidentally discovered unilateral, punctate, or coarse lesions of unclear etiology. Most calcified adrenal tumors are benign and <20% malignant or pheochromocytomas.

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.

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.

Objective Benign adrenal cysts are rare lesions of the adrenal glands. Limited data are available to guide management. We aimed to describe the presentation and outcomes of patients with benign adrenal cysts. Design Retrospective longitudinal cohort study. Methods Consecutive patients with histologically or radiologically confirmed adrenal cysts between 1995 and 2021 were identified. Pheochromocytomas and malignancy were excluded. Results Benign adrenal cysts were diagnosed in 92 patients (53, 57% women) at a median age of 45 years. Mode of discovery was incidental on imaging in 81 (88%), symptoms of mass effect in 9 (9.8%), and others in 2 (2.2%). Majority (89, 97%) of patients had unilateral cysts (45 right, 44 left) with a median size of 48 mm (range 4–200) at diagnosis. On imaging, most cysts were round/oval (85.4%), homogenous (83.2%) lesions with calcifications (64.0%) and no vascular enhancement (97.7%). During a median follow-up of 65 months (range 7–288), adrenal cysts demonstrated minimal enlargement (median size change 6 mm, median growth rate 2 mm/year). On hormonal evaluation, 10% (5/50 tested) had an abnormal overnight dexamethasone suppression test, and 9.5% (4/42 tested) had an abnormal case detection testing for primary aldosteronism. Patients treated with adrenalectomy (46, 50%) were younger (36.9 years vs 50.8 years, P = 0.0009) and had more rapidly enlarging cysts (median growth rate 5.5 mm/year vs 0.4 mm/year, P = 0.0002). Conclusion Benign adrenal cysts are usually incidentally discovered, non-functional, homogenous lesions without vascular enhancement that demonstrate minimal growth. Adrenalectomy should be reserved for patients with heterogeneous lesions, abnormal hormonal evaluation, or those with mass effect symptoms.

Abstract Purpose Craniopharyngiomas are nonmalignant sellar and parasellar tumors exhibiting a bimodal age distribution. While the outcomes following treatment in patients with childhood-onset craniopharyngiomas are well characterized, similar information in adult-onset craniopharyngiomas is limited. We aimed to describe the long-term outcomes (weight and metabolic parameters, mortality) in patients with adult-onset craniopharyngioma following treatment. Methods: Patients with adult-onset craniopharyngioma with initial treatment (1993–2017) and > 6 months of follow-up at our institution were retrospectively identified. Body mass index (BMI) categories included obese (BMI ≥ 30 kg/m2), overweight (BMI 25-29.9 kg/m2), and normal weight (BMI < 25 kg/m2). Results For the 91 patients with adult-onset craniopharyngioma (44% women, mean diagnosis age 48.2 ± 18 years) over a mean follow-up of 100.3 ± 69.5 months, weight at last follow-up was significantly higher than before surgery (mean difference 9.5 ± 14.8 kg, P < 0.001) with a higher percentage increase in weight seen in those with lower preoperative BMI [normal weight (20.7 ± 18%) vs. overweight (13.3 ± 18.0%) vs. obese (6.4 ± 15%), P = 0.012. At last follow-up, the prevalence of obesity (62 vs. 40.5%, P = 0.0042) and impaired glucose metabolism (17.4% vs. 34%, P = 0.017) increased significantly. All-cause mortality was 12%, with the average age of death 71.9 ± 19.7 years (average U.S. life expectancy 77.7 years, CDC 2020). Conclusion Patients with adult-onset craniopharyngioma following treatment may experience weight gain, increased prevalence of obesity, impaired glucose metabolism, and early mortality. Lower preoperative BMI is associated with a greater percentage increase in postoperative weight.