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ContextLimited information is available concerning the genetic spectrum of pheochromocytoma and paraganglioma (PPGL) patients in South America. Germline SDHB large deletions are very rare worldwide, but most of the individuals harboring the SDHB exon 1 deletion originated from the Iberian Peninsula.ObjectiveOur aim was to investigate the spectrum of SDHB genetic defects in a large cohort of Brazilian patients with PPGLs.MethodsGenetic investigation of 155 index PPGL patients was performed by Sanger DNA sequencing, multiplex ligation-dependent probe amplification, and/or target next-generation sequencing panel. Common ancestrality was investigated by microsatellite genotyping with haplotype reconstruction, and analysis of deletion breakpoint.ResultsAmong 155 index patients, heterozygous germline SDHB pathogenic or likely pathogenic variants were identified in 22 cases (14.2%). The heterozygous SDHB exon 1 complete deletion was the most frequent genetic defect in SDHB, identified in 8 out of 22 (36%) of patients. Haplotype analysis of 5 SDHB flanking microsatellite markers demonstrated a significant difference in haplotype frequencies in a case-control permutation test (P = 0.03). More precisely, 3 closer/informative microsatellites were shared by 6 out of 8 apparently unrelated cases (75%) (SDHB-GATA29A05-D1S2826-D1S2644 | SDHB-186-130-213), which was observed in only 1 chromosome (1/42) without SDHB exon 1 deletion (X2 = 29.43; P < 0.001). Moreover, all cases with SDHB exon 1 deletion had the same gene breakpoint pattern of a 15 678 bp deletion previously described in the Iberian Peninsula, indicating a common origin.ConclusionThe germline heterozygous SDHB exon 1 deletion was the most frequent genetic defect in the Brazilian PPGL cohort. Our findings demonstrated a founder effect for the SDHB exon 1 deletion in Brazilian patients with paragangliomas.

Objective Few and conflicting reports have characterized the genetics of paediatric pheochromocytomas and paragangliomas (PPGLs). This study aimed to investigate the clinical and genetic features of Brazilian children with PPGL. Patients and methods This study included 25 children (52% girls) with PPGL. The median age at diagnosis was 15 years (4-19). The median time of follow-up was 145 months. The genetic investigation was performed by Sanger DNA sequencing, multiplex ligation-dependent probe amplification and/or target next-generation sequencing panel. Results Of the 25 children with PPGL, 11 (44%), 4 (16%), 2 (8%), 1 (4%) and 7 (28%) had germline VHL pathogenic variants, SDHB, SDHD, RET and negative genetic investigation, respectively. Children with germline VHL missense pathogenic variants were younger than those with SDHB or SDHD genetic defects [median (range), 12 (4-16) vs. 15.5 (14-19) years; P = .027]. Moreover, 10 of 11 cases with VHL pathogenic variants had bilateral pheochromocytoma (six asynchronous and four synchronous). All children with germline SDHB pathogenic variants presented with abdominal paraganglioma (one of them malignant). The two cases with SDHD pathogenic variants presented with head and neck paraganglioma. Among the cases without a genetic diagnosis, 6 and 2 had pheochromocytoma and paraganglioma, respectively. Furthermore, metastatic PPGL was diagnosed in four (16%) of 25 PPGL. Conclusions Most of the paediatric PPGL were hereditary and multifocal. The majority of the affected genes belong to pseudohypoxic cluster 1, with VHL being the most frequently mutated. Therefore, our findings impact surgical management and surveillance of children with PPGL.

Familial primary aldosteronism (PA) is rare and mostly diagnosed in early-onset hypertension (HT). However, ‘sporadic’ bilateral adrenal hyperplasia (BAH) is the most frequent cause of PA and remains without genetic etiology in most cases. Our aim was to investigate new genetic defects associated with BAH and PA. We performed whole-exome sequencing (paired blood and adrenal tissue) in six patients with PA caused by BAH that underwent unilateral adrenalectomy. Additionally, we conducted functional studies in adrenal hyperplastic tissue and transfected cells to confirm the pathogenicity of the identified genetic variants. Rare germline variants in phosphodiesterase 2A (PDE2A) and 3B (PDE3B) genes were identified in three patients. The PDE2A heterozygous variant (p.Ile629Val) was identified in a patient with BAH and early-onset HT at 13 years of age. Two PDE3B heterozygous variants (p.Arg217Gln and p.Gly392Val) were identified in patients with BAH and HT diagnosed at 18 and 33 years of age, respectively. A strong PDE2A staining was found in all cases of BAH in zona glomerulosa and/or micronodules (that were also positive for CYP11B2). PKA activity in frozen tissue was significantly higher in BAH from patients harboring PDE2A and PDE3B variants. PDE2A and PDE3B variants significantly reduced protein expression in mutant transfected cells compared to WT. Interestingly, PDE2A and PDE3B variants increased SGK1 and SCNN1G/ENaCg at mRNA or protein levels. In conclusion, PDE2A and PDE3B variants were associated with PA caused by BAH. These novel genetic findings expand the spectrum of genetic etiologies of PA.

Objectives To develop a preoperative nomogram that would predict the risk of a postoperative complication for pheochromocytoma patients undergoing adrenalectomy using an international database. Methods We retrospectively analyzed preoperative variables and postoperative outcomes in patients who underwent adrenalectomy for pheochromocytoma in three institutions from 2000 to 2017. Internal validation of a generated nomogram was carried out with receiver operating characteristics, calibration plots, and decision curve analyses. Results A total of 153 patients who had undergone 166 adrenalectomies were included in the study. Overall, post-adrenalectomy complications were seen in 30% of patients, whereas 9.6% of patients sustained a Clavien ≥3a complication. Independent predictors of a complication were a history of hypertension, body mass index, tumor size, and Charlson Comorbidity Index score. On internal validation, the multivariable model generated a nomogram that predicted a postoperative complication or clinically hemodynamic event with an area under the curve of 0.86, showed good calibration and had an overall net benefit. Conclusions An internally validated nomogram combining body mass index, Charlson Comorbidity Index score and tumor size can predict the probability of a post-adrenalectomy complication in those with and without hypertension. The model, the first of its kind in pheochromocytoma surgery, identifies patients at risk of a postoperative complication at the time of their presentation with pheochromocytoma.

While multiple studies have demonstrated that minimally invasive surgical (MIS) techniques are a safe and efficacious approach to adrenalectomy for pheochromocytomas (PC), these studies have only been small comparative studies. The aim of this multi-institutional study is to compare perioperative outcomes between open and MIS, stratified by robotic and conventional laparoscopic, techniques in the surgical management of PC. We retrospectively evaluated patients who underwent adrenalectomy for PCs from 2000 to 2017 at three different institutions. Clinical, perioperative, and pathologic parameters were analyzed using t test, Chi square, and Fisher exact statistical measures. Of the 156 adrenalectomy cases performed, 26 (16.7%) were with an open approach and 130 (83.3%) using MIS techniques. Of the MIS procedures, 41 (31.5%) were performed robotically and 89 (68.5%) performed laparoscopically without robotic assistance. Demographic and clinical parameters were similar between the open and MIS groups. Patients, who underwent MIS procedure had a lower complication rate (p = 0.04), shorter hospitalization (p = 0.02), shorter operative time (p < 0.001), and less blood loss (p = 0.002) than those who underwent open surgical resection. Conventional laparoscopic and robotic operative approaches resulted in similar complication rates, length of hospitalization, and blood loss. Our study is one of the largest cohorts comparing the perioperative outcomes between conventional laparoscopic and robotic adrenalectomies in patients with PC. Our results support that MIS techniques have potentially lower morbidity compared to open techniques, while laparoscopic and robotic approaches have similar perioperative outcomes.

Context Primary aldosteronism (PA) screening relies on an elevated aldosterone to renin ratio with a minimum aldosterone level, which varies from 10 to 15 ng/dL (277-415.5 pmol/L) using immunoassay. Objective To evaluate intra-individual coefficient of variation (CV) of aldosterone and aldosterone to direct renin concentration ratio (A/DRC) and its impact on PA screening. Methods A total of 671 aldosterone and DRC measurements were performed by the same chemiluminescence assays in a large cohort of 216 patients with confirmed PA and at least 2 screenings. Results The median intra-individual CV of aldosterone and A/DRC was 26.8% and 26.7%. Almost 40% of the patients had at least one aldosterone level 2 ng/dL/µIU/mL had a true positive rate for PA diagnosis of 94.4% and 98.4% when based on 1 or 2 assessments, respectively. CV of aldosterone and A/DRC were not affected by sex, use of interfering antihypertensive medications, PA lateralization, hypokalemia, age, and number of hormone measurements. Conclusion Aldosterone concentrations had a high CV in PA patients, which results in an elevated rate of false negatives in a single screening for PA. Therefore, PA screening should be based on at least 2 screenings with concomitant aldosterone and renin measurements.

Background Pheochromocytomas and paragangliomas (PPGLs) have the highest degree of heritability among endocrine tumors. Currently, ∼40% of PPGL individuals have a genetic germline pathogenic variant and exist at least 12 different genetic syndromes related to these tumors. Pathogenic variants in the Succinate Dehydrogenase Complex Subunit B (SDHB) gene account for about 10% of PPGL cases. Moreover, SDHB pathogenic variants are the most well-established risk factor to predict metastatic disease (40%-50% of cases). Germline SDHB large deletions are very rare worldwide, but SDHB exon 1 deletion has been reported in patients with PPGLs from Portugal and Spain. Indeed, a putative founder effect for SDHB exon 1 deletion was suggested in PPGL patients from Iberian Peninsula. Aim To investigate a putative founder effect for SDHB exon 1 deletion. Methods Eighteen unrelated Brazilian patients with germline heterozygous SDHB pathogenic variants were included. Additionally, two unrelated individuals with SDHB exon 1 complete deletion from Argentina were studied. SDHB pathogenic variants were investigated by automated SAGER sequencing, multiplex ligation-dependent probe amplification (SALSA MLPA Probemix P226 SDH) and/or high-throughput sequencing. Five SDHB flanking microsatellite markers at chromosome 1p (D1S2697, GATA29A05, D1S2826, D1S2644, and D1S199) were used to investigate if patients carrying this deletion have a common origin. Haplotypes were reconstructed using the PHASE algorithm (v. 2.1). A control group comprising 26 unrelated Brazilian individuals was also studied. Results Among 18 Brazilian patients with germline SDHB pathogenic variants, heterozygous SDHB exon 1 complete deletion was identified in 6 of them (33% of the cases). The remaining 12 patients presented intragenic SDHB pathogenic variants without hotspot location. All Brazilian index patients with SDHB exon 1 deletion presented with paraganglioma, located mostly in the abdomen (4 abdominal; one thoracic; two head and neck and one colonic). Median age was 31.5 years and metastatic disease occurred in 3 (50%) of them. Haplotype analysis showed that 4 apparently unrelated Brazilian patients (4 out of 6 cases, 67%) shared a common allele (SDHB-GATA29A05-D1S2826-D1S2644-D1S199 | SDHB-186-130-213-102), which was not seen in chromosomes without the SDHB exon 1 deletion (p= 0.01). The two cases from Argentina did not have this haplotype, suggesting that SDHB exon 1 deletion in Argentina have a different origin. Conclusion SDHB exon 1 complete deletion was the most frequent SDHB defect in our cohort. Our findings indicate a founder effect for SDHB exon 1 complete deletion in Brazilian patients with paraganglioma. Support: Sao Paulo Research Foundation (FAPESP) grant 2019/15873-6 Presentation: Saturday, June 11, 2022 1:24 p.m. - 1:29 p.m., Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

Context Von Hippel-Lindau (VHL) disease is an autosomal dominant syndrome caused by germline mutations in the VHL gene. Guidelines recommend pheochromocytoma (PHEO) biochemical screening should start at age 5 years. Objective Genotype–phenotype correlations in VHL, focusing on PHEO penetrance in children, were studied. Design We retrospectively evaluated 31 individuals (median age at diagnosis was 26 years) with diagnosed VHL disease. Results PHEO was diagnosed in six children with VHL. A large PHEO (5 cm) was detected in a 4-year-old boy with p.Gly114Ser mutation. PHEO penetrance was 55% starting at age 4 years. VHL missense mutations were identified in 11 of 22 families (50%), frameshift mutations in four (18.2%), stop codon in three (13.6%), splicing site in two (9.1%), and large gene deletion in two (9.1%). The codon 167 (n = 10) was a hotspot for VHL mutations and was significantly associated with PHEO (90% vs. 38%; P = 0.007). PHEOs and pancreatic neuroendocrine tumors (PNETs) were strongly associated with VHL missense mutations compared with other mutations (89.5% vs. 0% and 73.7% vs. 16.7%; P = 0.0001 and 0.002, respectively). In contrast, pancreatic cysts (91.7% vs. 26.3%; P = 0.0001), renal cysts (66.7% vs. 26.3%; P = 0.027), and central nervous system hemangioblastomas (91.7% vs. 47.3%; P = 0.012) were more frequent in VHL with nonmissense mutations. Conclusion VHL missense mutations were highly associated with PHEO and PNETs. Our data support that in children with VHL harboring missense mutations, biochemical screening for PHEO should be initiated at diagnosis.

Purpose This prospective study presents the results of a new approach in the treatment of primary macronodular adrenal hyperplasia (PMAH), with simultaneous total adrenalectomy of the larger adrenal gland and partial adrenalectomy of the contralateral adrenal gland (adrenal-sparing surgery). Materials and Methods We performed a prospective study including 17 patients with PMAH treated surgically with adrenal-sparing surgery in a tertiary referral hospital, with a median follow-up of 41 months. Clinical, hormonal, and genetic parameters were evaluated before surgery and during follow-up. All patients had at least 1 radiological examination before and after the procedure. Results Among the 17 patients, all but 1 patient had complete hypercortisolism control, and 12 recovered normal adrenal function after surgery. Significant improvement in clinical parameters was observed: weight loss (P = .004); reduction of both systolic (P = .001) and diastolic (P = .001) blood pressure; and reduction in the number of antihypertensive drugs (P < .001). Intra-, peri-, and postoperative complications were not observed. Conclusion Adrenal-sparing surgery is a safe and feasible procedure to treat patients with PMAH, providing a substantial chance of hypercortisolism control without the disadvantages of lifetime corticosteroid replacement.

Primary aldosteronism (PA) is the most common cause of endocrine hypertension. PA subtypes include bilateral hyperplasia and unilateral PA, typically aldosterone-producing adenomas. Adrenal venous (AV) sampling (AVS) is a key step to define PA subtype and guide PA management. According current PA guidelines, most PA patients should undergo AVS, which is a challenging procedure, especially in terms of successfully cannulating the right AV. The aim of this study was to report a single tertiary center experience with AVS in PA patients. We retrospectively evaluated 84 AVS from 1984 to 2019. Sequential AVS was performed by an experienced interventional radiologist. AV and inferior vena cava (IVC) samples were obtained under cosyntropin continuous infusion. Successful catheterization was defined by a selectivity index [SI= AV/IVC cortisol (C) concentrations] ≥5. Unilateral disease was defined by a lateralization index [LI= aldosterone (A)/C ratio in the dominant AV divided by A/C in the non-dominant AV] ≥4. The relative aldosterone secretion index (RASI= A/C ratio in AV divided by A/C in IVC) was calculated in each side. A RASI

Pheochromocytomas and paragangliomas (PPGLs) are neuroendocrine tumors derived from chromaffin cells. At least 30% of PPGL patients have hereditary predisposition. PPGLs in children are more often hereditary, multiple and extra-adrenal. To date, more than 14 tumor-susceptibility genes have been reported: Cluster 1 or hypoxic (VHL, SDHB, SDHD, SDHC, SDHA, SDHAF2, FH, ENGL1 and HIF2A) and cluster 2 (RET, NF1, TMEM127 and MAX). The aim of this study was to evaluate clinical and molecular aspects of a Brazilian cohort of pediatric patients with PPGLs. Out of 262 patients with PPGLs, 26 (9 %) were diagnosed before 19 yrs of age (16 males and 10 females), with a median age of 14.5 yrs (range, 4 to 18). Genetic investigation was performed in 19 patients: 14 by automated Sanger sequencing (VHL, SDHB, SDHD and RET genes) and 5 by a custom next-generation sequencing (NGS) panel including all genes previously associated with germline mutations in PPGLs. Median tumor size was 5.5 cm (1.7 to 16). Pheochromocytomas (PHEOs), paragangliomas (PGLs) or both were diagnosed in 46%, 31% and 23% of the patients, respectively. Bilateral PHEOs were diagnosed in 61% of the cases, most of them asynchronous (75%). Genetic diagnosis was confirmed in 14 out of 19 (74%) patients and all variants were found in heterozygous state: 8 VHL missense mutations from 6 kindreds (p.R167W in 2 kindreds, p.R167Q in one and p.G114S in 3); 3 SDHB mutations (p.C98Y, c.201-2A>G and p.L180L); 2 SDHD mutations (p.Y144_H145del and p.Q121*); and one RET mutation (p.C634R). All 8 VHL patients had bilateral PHEOs and 3 of them had also abdominal PGLs. All patients with SDHB mutations had abdominal PGLs. Two patients with SDHD mutation had head and neck paraganglioma (one of them had unilateral PHEO). Genetic investigation by NGS Panel was negative in all 5 cases: 2 malignant PPGLs (one PHEO and one PGL) and 3 PHEOs. Four out of 26 (15%) pediatric PPGLs were malignant: 2 with SDHB mutation and 2 with negative screening (one PHEO and one PGL). In conclusion, the majority of pediatric PPGLs (74%) were hereditary and almost exclusively caused by mutations in hypoxic genes. VHL (PHEOs) and SDHB (only PGLs) were the most frequent affected genes in this cohort of pediatric PPGLs. Support: CAPES grant to Petenuci J.

Introduction: Masses in adrenal topography are diagnosed frequently due to the increase in radiological imaging in clinical practice. Adrenal incidentalomas occur between 4% and 10% of the patients above 50 years undergoing abdominal imaging, and the majority are benign pathologies. Objective: To analyze the characteristics of the masses located in adrenal gland topography not originating from the adrenal gland. Methods: We retrospectively assessed patients from our tertiary hospital who underwent surgical treatment for masses in adrenal gland topography between 2006 and 2018. All patients had hormonal evaluations, according to the European and American Societies of Endocrinology guidelines. Two expert radiologists reviewed all images. Forty-six patients were included in the study, and the surgical specimens were analyzed by the same experienced pathologist. Patients with confirmed adrenocortical carcinoma (ACC) were excluded from this cohort. Results: Thirty-two (69.6%) patients were female. The median age was 49.5 years old (range 18-82yo). Abdominal or lumbar pain was the most frequent reason for medical investigation (43.5%). Adrenal incidentalomas represented 38.4% of the cohort. None of these patients had any clinical signs of adrenal hyperfunction, nor hormonal alteration. Twenty-four patients (52.17%) presented a mass on the left side, and only two cases presented bilateral adrenal masses. The median size was 8.6cm (1.3-18cm). The mean of Hounsfield Units (HU) on a non-contrasted CT was 25HU (0-50HU). Several etiologies were found: 8 cases (18%) of ganglioneuroma; 6 cases (13,5%) of adrenal cysts; 4 cases (9%) of leiomyosarcoma and adrenal hemorrhage; 3 cases (6.5%) of infectious disease; 2 cases (4.5%) of lymphangioma, schwannoma, and sarcoma. We also found single cases of renal cell carcinoma, poorly differentiated small cell neuroendocrine carcinoma, hepatocellular carcinoma, high grade dedifferentiated liposarcoma, epithelioid neoplasia, epithelial neoplasia with neuroendocrine differentiation, malignant peripheral nerve sheath tumor of the adrenal gland, poorly differentiated neuroblastoma, high grade lymphoma, myelolipoma, acute splenitis, arteriovenous malformation, and prostate cancer metastasis. Discussion and Conclusion: Ganglioneuroma was the most frequent diagnosis in adrenal incidentalomas in our cohort. In general, these conventional radiological exams could not differentiate lesions originated in the adrenal glands from lesions of other origins. In this large cohort, we could identify non-adrenal origin in approximately 45% of the patients with masses in the adrenal topography.

Background: Aldosterone producing adenomas (APAs) are the most common cause of unilateral primary aldosteronism (PA). In most cases, APAs present as small ( Clinical Cases: Case 1. A 33-yr-old man was referred to investigate resistant hypertension (HT). Biochemical evaluation revealed normal K levels, aldosterone (A) of 14.7 ng/dl, renin of 2.1 mUI/L (normal, 4.4-46.1) and A/R ratio of 24.8. Confirmatory testing confirmed PA diagnosis. Hypercortisolism investigation revealed a non-suppressible cortisol after an overnight 1 mg low-dose dexamethasone suppression (8.3 μg/dL), abnormal midnight salivary cortisol, and normal urinary free cortisol, plasma DHEAS and ACTH levels. Computed tomography (CT) scan showed a well-limited mass in left adrenal, measuring 5.8 cm with pre-contrast density of 30 HU and absolute wash-out of 72%. After left laparoscopic adrenalectomy, hydrocortisone was started and adrenal insufficiency confirmed by basal cortisol 1/3 diffuse architecture). CYP11B2 staining was positive in 30% and Ki67 in 5% of the cells. She presented biochemical cure of PA and improvement in HT control. Genetic investigation for somatic KCNJ5, ATP1A1, ATP2B3 and CTNNB1 was negative in both cases. Conclusion: We describe two rare cases of APAs that presented as large and suspicious tumors, without somatic mutations in genes associated with APAs.

Introduction: Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors arising from chromaffin cells. More than 30% of patients with PPGLs have a hereditary predisposition. Malignancy in PPGLs is defined by the presence of local invasion or metastasis in nonchromaffin tissues. Germline SDHB mutations are found in approximately 40% of malignant PPGLs, mainly paragangliomas (PGLs). However, SDHB mutations are not a prognostic factor in malignant PPGLs. To date, no genotype-phenotype correlation has been reported in malignant PPGLs associated with SDHB mutations. Aim: To investigate clinical and imaging features of patients with malignant PGLs harboring germline SDHB exon 1 deletion or splicing site mutation. Methods: We retrospectively evaluated 22 unrelated individuals with malignant PPGLs. Six out of 22 (27%) malignant PPGLs harbored germline SDHB mutations. Three patients had SDHB exon 1 deletion and 3 splicing site mutation (2 with c.201-2A>G and one with c.423 + 1G>A). All SDHB defects were classified as likely pathogenic. Results: In the exon 1 deletion group, 2 patients had abdominal PGLs (one also had a neck PGL) and one had only head and neck PGLs. In the splicing site mutation group, all 3 patients had abdominal PGLs (one also had a neck PGL). Median age at diagnosis was 26 yrs (16 to 45) and 33 yrs (26 to 53) in the exon 1 deletion and splicing mutation groups, respectively. Two patients (one in each group) had metastasis at diagnosis. All 6 patients had bone metastasis, but liver and/or lung metastasis were more frequent in patients with SDHB exon 1 deletion (66 vs. 33%). Interestingly, metastasis from malignant PGLs harboring SDHB splicing site mutations were 131I-metaiodobenzylguanidine (MIBG) avid in all cases, whereas metastatic lesions from malignant PGLs harboring SDHB exon 1 deletion did not present any MIBG uptake on diagnostic imaging studies. Therefore, all 3 patients with SDHB exon 1 deletion were treated with chemotherapy (cyclophosphamide, vincristine and dacarbazine). In contrast, all 3 patients with splicing site mutations have been treated with MIBG therapy. Median follow-up was 87 months (8 to 360 months). Only one patient (exon 1deletion group) died because of disease progression. Conclusion: We first demonstrated here that germline SDHB exon 1 deletion is associated with absence of MIBG uptake in malignant PGLs. This finding needs to be confirmed in an expanded cohort of malignant PPGLs.

Background: Primary aldosteronism (PA) is the most common cause of endocrine hypertension (HT). PA subtypes include aldosterone-producing adenomas (APA) and bilateral adrenal hyperplasia. To date, few PA patients with bilateral adenomas have been reported, but only one case was well characterized by anatomopathological analysis and clinical outcome after adrenal sparing surgery (1). Clinical case: A 53-year-old woman was referred to investigate resistant HT and hypokalemia. (3.0 mEq/L). PA screening revealed aldosterone (A) of 37.9 ng/dL, renin (R) < 1.6 (4.4-46.1 mUI/L), A/R ratio of 24.8. Confirmatory testing confirmed PA diagnosis: seated saline infusion test (A= 83.3 ng/dL) and intravenous furosemide test (R= 3.1 mUI/L; positive test Conclusion: We herein described a very rare case of PA caused by bilateral-producing adenomas, confirmed by AVS and CYP11B2 staining after adrenal sparing surgery.

Background: Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with an unfavorable prognosis. Despite the poor prognosis in the majority of patients, no improvements in treatment strategies have been achieved, largely due to the rarity of these tumors. Therefore, the discovery of new prognostic biomarkers that could guide and improve the management of patients with ACC is of enormous interest. Sterol-O-Acyl Transferase 1 (SOAT1) is involved in cholesterol esterification in adrenocortical cells. Recently, it was demonstrated that SOAT1 inhibition leads to impaired steroidogenesis and cell viability in ACC [1]. There are no studies so far addressing the impact of SOAT1 protein expression in ACC prognosis and clinical outcomes. Methods: We evaluated SOAT1 protein expression by immunohistochemistry (ab39327; 1:4000; Abcam, EUA) in a tissue microarray of 107 adrenocortical carcinomas (Weiss score ≥ 3) from adult patients treated in a single tertiary center in Brazil. Immunohistochemistry results were evaluated through a semiquantitative approach by two independent pathologists. We aimed to evaluate the correlation of SOAT1 protein expression with clinical and biochemical parameters, surgical specimen histological characteristics, recurrence free-survival, progression free-survival and overall survival. Results: SOAT1 protein expression was heterogenous in this cohort; 38% of ACCs demonstrated strong SOAT1 protein expression while 62% demonstrated weak or absent SOAT1 protein expression. Strong SOAT1 protein expression correlates with known features of high aggressiveness in ACC, such as excessive tumor cortisol secretion (p= 0.007), advanced disease stage [ENSAT 3 and ENSAT 4 (p= 0.009)] and high Ki67 index (0.008). On multivariate analysis, strong SOAT1 protein expression was an independent predictor of lower overall survival (HR 1.71, CI 95% 1.05-2.92; p= 0.04) when considering all cases (n= 107) and of lower progression free survival (HR 3.05, CI 95% 1.05-8.85; p= 0.04) in patients with metastatic disease at diagnosis (n= 22). Conclusions: Our findings demonstrated that SOAT1 protein expression has prognostic value in ACC and reinforce the importance of investigating SOAT1 as a possible therapeutic target for patients with ACC. Multicentric prospective studies including a larger number of patients are needed in order to validate and consolidate the results found in this cohort. References: 1. Sbiera S, Leich E et al. Mitotane inhibits Sterol-O-Acyl Transferase 1 Triggering Lipid-Mediated Endoplasmic Reticulum Stress and Apoptosis in Adrenocortical Carcinoma Cells. Endocrinology. 2015; 156 (11):3895-908.

Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with an unfavorable prognosis. Despite the poor prognosis in the majority of patients, no improvements in treatment strategies have been achieved. Therefore, the discovery of new prognostic biomarkers is of enormous interest. Sterol-O-acyl transferase 1 (SOAT1) is involved in cholesterol esterification and lipid droplet formation. Recently, it was demonstrated that SOAT1 inhibition leads to impaired steroidogenesis and cell viability in ACC. To date, no studies have addressed the impact of SOAT1 expression on ACC prognosis and clinical outcomes. We evaluated SOAT1 expression by quantitative real-time polymerase chain reaction and immunohistochemistry in a tissue microarray of 112 ACCs (Weiss score &ge, 3) from adults treated in a single tertiary center in Brazil. Two independent pathologists evaluated the immunohistochemistry results through a semiquantitative approach (0&ndash, 4). We aimed to evaluate the correlation between SOAT1 expression and clinical, biochemical and anatomopathological parameters, recurrence-free survival (RFS), progression-free survival (PFS), and overall survival (OS). SOAT1 protein expression was heterogeneous in this cohort, 37.5% of the ACCs demonstrated a strong SOAT1 protein expression (score &gt, 2), while 62.5% demonstrated a weak or absent protein expression (score &le, 2). Strong SOAT1 protein expression correlated with features of high aggressiveness in ACC, such as excessive tumor cortisol secretion (p = 0.01), an advanced disease stage [European Network for the Study of Adrenal Tumors (ENSAT) staging system 3 and 4 (p = 0.011)] and a high Ki67 index (p = 0.002). In multivariate analysis, strong SOAT1 protein expression was an independent predictor of a reduced OS (hazard ratio (HR) 2.15, confidence interval (CI) 95% 1.26&ndash, 3.66, p = 0.005) in all patients (n = 112), and a reduced RFS (HR 2.1, CI 95% 1.09&ndash, 4.06, p = 0.027) in patients with localized disease at diagnosis (n = 83). Our findings demonstrated that SOAT1 protein expression has prognostic value in ACC and reinforced the importance of investigating SOAT1 as a possible therapeutic target for patients with ACC.

Purpose: To investigate risk factors for complications in patients undergoing adrenalectomy. Materials and Methods: A retrospective search of our institutional database was performed of patients who underwent adrenalectomy, between 2014 and 2018. Clinical parameters and adrenal disorder characteristics were assessed and correlated to intra and post-operative course. Complications were analyzed within 30-days after surgery. A logistic regression was performed in order to identify independent predictors of morbidity in patients after adrenalectomy. Results: The files of 154 patients were reviewed. Median age and Body Mass Index (BMI) were 52-years and 27.8kg/m2, respectively. Mean tumor size was 4.9±4cm. Median surgery duration and estimated blood loss were 140min and 50mL, respectively. There were six conversions to open surgery. Minor and major post-operative complications occurred in 17.5% and 8.4% of the patients. Intra-operative complications occurred in 26.6% of the patients. Four patients died. Mean hospitalization duration was 4-days (Interquartile Range: 3-8). Patients age (p=0.004), comorbidities (p=0.003) and pathological diagnosis (p=0.003) were independent predictors of post-operative complications. Tumor size (p

Primary aldosteronism (PA) is the most common cause of endocrine hypertension. The 2016 Endocrine Society’s Guideline for PA management recommend that patients with a positive screening undergo one or more confirmatory tests to definitively confirm or exclude the diagnosis. Confirmatory testing procedures include oral sodium loading, saline infusion test (SIT), fludrocortisone suppression, captopril test (CT) and furosemide upright test (FUT). The FUT, mainly proposed by the Japan Endocrine Society, does not have limitation in patients with severe uncontrolled hypertension and heart failure. A positive FUT is defined as a plasma renin activity (PRA)

Background: Pheochromocytomas and paragangliomas (PPGLs) are neuroendocrine tumors derived from chromaffin cells. More than 30% of patients with PPGL have a hereditary predisposition. To date, at least 14 tumor susceptibility genes have been described. Mutations in the succinate dehydrogenase complex iron sulfur subunit B gene (SDHB) are more associated with paragangliomas and metastatic disease. Patients who are young, with larger tumors (>6 cm), positive genetic testing (especially SDHB) or paraganglioma have a higher risk of metastasis development. Case Report: A 14-yr-old boy was referred to investigate severe hypertension and paroxysmal headache, pallor and tachycardia. Biochemical testing for catecholamine-secreting PPGLs showed: 24h urine metanephrines 1.9 µg (normal range, 0.05 to 1.2), plasma normetanephrine 13.3 nmol/L (A (p.L180=), involving a G>A transition in the last nucleotide of SDHB exon 5. This synonymous variant results in alternative splicing of the SDHB primary transcript. This germline variant was previously reported in a 12-yr-old patient with isolated jugulotympanic paraganglioma, but it has not been associated with catecolamine-secreting paraganglioma. Neck MRI revealed no abnormalities in our patient. Conclusion: We report here a synonymous pathogenic variant in SDHB exon 5 associated with an abdominal functioning paraganglioma. Annual screening for multifocal disease (abdominal and neck PPGLs) and malignancy should be performed.

Primary aldosteronism (PA) is the most common cause of endocrine hypertension (HT) with an estimated prevalence of 10% in referred populations and 15–20% in patients with resistant HT. Aldosterone-producing adenomas are the most common cause of unilateral PA. Primary unilateral adrenal hyperplasia (PUH) is a rare cause of PA, but is probably underestimated. PUH can be diffuse or nodular, with poorly capsulated micronodules. To date, there is a paucity of data characterizing this condition. In this study, our aim was to report the clinical and imaging features of patients with PA caused by PUH. We retrospectively evaluated clinical, imaging and histopathological data of 183 PA patients. PUH was diagnosed in 9 out of 183 patients (5%). All patients had biochemical cure of PA after unilateral adrenalectomy and anatomopathological analysis showed micronodular adrenal hyperplasia in all cases. At the diagnosis, median age was 52 yrs, ranging from 33 and 74 yrs (6 men and 3 women). Hypokalemia was reported in 63% of the cases. Aldosterone/plasmatic renin activity ratio was 123.6 (range, 52 to 379). The median duration of HT was 18 yrs (range, 1 to 52). Because of HT duration before diagnosis, only a patient had HT cure after adrenalectomy. The median follow-up was 46 months (7 to 117 months). Computed tomography (CT) accuracy to determine the lateralization was 67%. The adrenal CT findings were: normal adrenals (n= 1), bilateral hyperplasia (n= 1; right incidentaloma 1.9 cm and left PUH 1.4 cm), unilateral hyperplasia (n= 1), bilateral nodules (n= 1) and unilateral nodules (n= 5; median 1.3 cm, from 0.9 to 1.5). Adrenal venous sampling was performed in 5 patients (successful rate 80%). In the remaining cases, surgery was guided by CT. PUH was in the left adrenal in 7 out of 9 cases (78%). Hot spot somatic mutations in aldosterone-driver genes (KCNJ5, ATP1A1, ATP2B3 and CTNNB1) were excluded by Sanger automated sequencing and the presence of chimeric CYP11B1/CYP11B2 gene was ruled out by long-PCR in all cases. In conclusion, PUH prevalence in our cohort was higher than previously reported. PUH was more frequent in men and in the left adrenal. The most common CT finding was a unilateral nodule smaller than 1.5 cm. However, CT accuracy was low and AVS should be the gold standard to define lateralization. Support: CNPq (403256/2016-0) to MQA; FAPESP (2017/13394-8) to MRC.

Background: Adrenocortical carcinoma (ACC) is a rare and, in the vast majority of cases, aggressive neoplasia. Even in cases of localized disease at the diagnosis in which complete surgical resection of the tumor is performed, rates of local and distant recurrence are very high. Aim: To retrospectively analyze the management and outcomes of cases that presented localized disease (Group 1) and metastatic disease at diagnosis (Group 2) followed in a single Institution. Results: Group 1 was formed by 23 cases and group 2 by 7 cases. In group 1, adjuvant treatment was initiated in 17 patients: 9 received adjuvant radiotherapy (ARDT) associated with mitotane and 8 patients received mitotane alone; six patients have been followed expectantly. Recurrence of the disease was observed in 70% of the cases (n=16). All had distant metastasis and 6 out of 16 also had local recurrence. Most frequent sites of metastasis were lung, liver and peritoneum, including a rare case of heart metastasis. All patients with recurrence received systemic chemotherapy. No patient who was followed without adjuvant treatment has recurred so far. The median recurrence free survival (RFS) and overall survival (OS) were 13 and 30 months, respectively. In group 2, 5 patients had only one site of metastasis at diagnosis (all of them presented lung metastases) and the remaining cases had two (lung and liver) or three sites (lung, liver and bone). In only one case neoadjuvant chemotherapy was the treatment of choice. In the remaining patients, primary tumor was resected and systemic chemotherapy and mitotane started after surgery. The number of chemotherapy regimens ranged from one to four. Median progression free survival (PFS) was 2 months (range, 0.9 to 11 months) and OS was 11 months (range, 0.9 to 30 months). Patients who had more than one metastatic site at diagnosis had a lower survival rate and the patient who underwent neoadjuvant chemotherapy presented the longest PFS (11 months). Conclusions: Group 1 cases analysis reinforces the high rate of disease recurrence in patients with localized disease despite adjuvant treatment with ARDT and mitotane. These findings support the need for multicenter clinical trials to investigate the benefit of systemic chemotherapy in an adjuvant setting in patients at high risk of recurrence. Regarding the metastatic patients at diagnosis, we emphasize the importance of a greater experience with neoadjuvant chemotherapy.

Background: PMAH is a cause of adrenal hypercortisolism and it is a genetic disease linked to ARMC5 gene in most cases. Heterogenous phenotypes due to cortisol secretion and also due to different germline mutations in the ARMC5 have been described in around the world. The diversity of the molecular second hits in adrenal nodules may be able to justify different clinical outcome in the same family. We report two sisters with the same germline mutation and different clinical outcome. Case: A 45-year-old female patient presented with clinical evidence of hypercortisolism. Metabolic syndrome has been evidenced since the age of 35. Hormonal data confirmed an autonomous cortisol secretion. Abdominal CT revealed a bilateral enlargement of adrenal glands with multiples nodules (up to 2 cm, with 10 Housfield Units). 18F-FDG-PET/CT identified a slight SUV (left SUV 3.4 and right SUV 2.7). A heterozygous germline pathogenic variant of ARMC5 was identified at exon 1: c.165_166insG, p.Ile58Asnfs*45 at BTB (POZ) domain associated with a somatic LOH of the germline mutation. In 2013, the patient underwent Adrenal Sparing Surgery (ASS). She presented an excellent control of metabolic syndrome associated with adrenal insufficiency (AI) for 12 months. After 2 years a clinical recurrence of hypercortisolism was observed and confirmed by laboratory data. A new abdominal 18F-FDG-PET/CT and CT showed an increase of SUV and enlargement of the right residual adrenal gland (SUV - 3.4). The patient was submitted to a partial right adrenalectomy. Interesting, she did not present total or partial AI after the second surgical procedure. Inversely, her sister (46 years of age), with classical Cushing´s syndrome and carrier of same germline mutation (with similar hormonal data and SUV of 18F-FDG-PET/CT), presented a long-term remission of hypercortisolism after ASS. The analysis of somatic mutation of ARMC5 revealed a new event c.2082_2088delCCCGCTC, p.Pro695Serfs*20 in heterozygous status at exon 6. Analysis of PMAH sections HE stained showed a different pattern in the proportion and distribution of clusters of compact cells (60%) relative to clear spongiocytic cells. Her sister presented 13% of compact cells, similar to the PMAH pattern. Discussion: The macronodules of PMAH are composed of clear spongiocytic cells which preferentially express 3βHSD steroidogenic enzyme, and small or compact cells, which differentially express CYP17A1 steroidogenic enzyme and are located in dispersed clusters among the clear cells. CYP17A1 has both 17α-hydroxylase activity and 17,20-lyase activity. Conclusion: The somatic events of ARMC5 should be considered and could be involved in heterogeneous cortisol secretion and clinical presentation in familial cases with different outcome. Further familial cohorts and functional studies should increase our understanding of this challenged adrenal disorder.

ContextPrimary aldosteronism (PA) is the most common cause of endocrine hypertension (HT). HT remission (defined as blood pressure ObjectiveTo determine clinical and molecular features associated with HT remission after adrenalectomy in patients with unilateral PA.MethodsWe retrospectively evaluated 100 patients with PA (60 women; median age at diagnosis 48 years with a median follow-up of 26 months). Anatomopathological analysis revealed 90 aldosterone-producing adenomas, 1 carcinoma, and 9 unilateral adrenal hyperplasias. All patients had biochemical cure after unilateral adrenalectomy. KCNJ5 gene was sequenced in 76 cases.ResultsKCNJ5 mutations were identified in 33 of 76 (43.4%) tumors: p.Gly151Arg (n = 17), p.Leu168Arg (n = 15), and p.Glu145Gln (n = 1). HT remission was reported in 37 of 100 (37%) patients. Among patients with HT remission, 73% were women (P = 0.04), 48.6% used more than three antihypertensive medications (P = 0.0001), and 64.9% had HT duration ConclusionThe presence of a KCNJ5 somatic mutation is an independent predictor of HT remission after unilateral adrenalectomy in patients with unilateral PA.

Background: Familial adenomatous polyposis (FAP) is an autosomal dominant condition caused by germline mutation in the tumor suppressor gene APC. FAP occurs in 1 to 10.000 individuals, and is characterized by hundreds to thousands of colonic adenomatous polyps with a high risk of developing into colorectal cancer. Extracolonic manifestations can be malignant or benign. The major causes of morbidity and mortality in patients with FAP are abdominal desmoid tumors, with incidences ranging between 7% and 17%. Adrenal incidentaloma are frequently discovered in these patients, generally as benign lesions when they undergo abdominal CT-scan in the course of surveillance. Adrenal lesions in FAP ranged from 7.4% to 16%. We described an unusual patient with FAP, associated with autonomous cortisol production due to bilateral adrenal tumors and the development of aggressive desmoid tumor after unilateral adrenalectomy. Clinical Case: A 33-years-old female FAP-patient presented with abdominal pain, weight gain (10kgs), humor instability, paroxysmal of chest pain, dizziness and tremors. The abdominal MRI showed a heterogeneous, left adrenal mass (9.0 x 7.9 x 6.7cm), suspected for malignant tumor, and right adrenal mass with 3.6 x 1.8 cm suggestive of adenoma. Abdominal CT and PETCTFDG revealed on the left adrenal lesion with 33UH and maxSUV 3.9 and a right adrenal lesion 13UH and maxSUV 3.1. Serum hormone levels were as follows: cortisol after DST (1mg-dexamethasone) 4.8 ug/Dl, ACTH 8,8pg/Ml with no other abnormal hormone secretion detected. Patient underwent left adrenalectomy. Histological analysis revealed Weiss 1, modified Weiss 2 and Ki67

The participation of aberrant receptors and intra-adrenal ACTH in hyperplastic tissue are considered mechanisms that regulate hypercortisolism in PMAH. Additionally, germline ARMC5 mutations have been described as the most frequent genetic abnormality found in patients diagnosed with PMAH. Previous functional studies analyzed ARMC5 role using H295R cells. Therefore, we investigated the role of ARMC5 in cell cultures obtained from PMAH nodules containing steroidogenic cells, aberrant receptors and intra-adrenal ACTH. ARMC5 silencing in non-mutated PMAH cell cultures decreased steroidogenesis-related genes and increased CCNE1 mRNA expression and proliferative capacity without affecting cell viability. Additionally, ARMC5 overexpression induced cell death in PMAH mutated cell cultures, thereby decreasing cell viability. We confirmed the role of ARMC5 as an important pro-apoptotic protein involved in PMAH-related steroidogenesis. We also report for the first time the involvement of ARMC5 in controlling proliferation and regulating cell cycle in PMAH cell cultures; these effects need to be explored further.

Purpose: To evaluate the role of ARDT after surgical resection of ACC. Materials and Methods: Records of patients from our institutional ACC database were retrospectively assessed. A paired comparison analysis was used to evaluate the oncological outcomes between patients treated with surgery followed by ARDT or surgery only (control). The endpoints were LRFS, RFS, and OS. A systematic review of the literature and meta-analysis was also performed to evaluate local recurrence of ACC when ARDT was used. Results: Ten patients were included in each Group. The median follow-up times were 32 months and 35 months for the ARDT and control Groups, respectively. The results for LRFS (p=0.11), RFS (p=0.92), and OS (p=0.47) were similar among subsets. The mean time to present with local recurrence was significantly longer in the ARDT group compared with the control Group (419±206 days vs. 181±86 days, respectively; p=0.03). ARDT was well tolerated by the patients; there were no reports of late toxicity. The meta-analysis, which included four retrospective series, revealed that ARDT had a protective effect on LRFS (HR=0.4; CI=0.17-0.94). Conclusions: ARDT may reduce the chance and prolong the time to ACC local recurrence. However, there were no benefits for disease recurrence control or overall survival for patients who underwent this complementary therapy.

The management of vesicoureteral reflux (VUR) is varied and remains controversial, which is likely because children with VUR have different risks for urinary tract infection or renal injury. Consequently, the treatment of VUR needs to be individualized based on the patient's characteristics. In this article, the authors review the medical and surgical management options for VUR in the pediatric population. The authors hope to provide a systematic approach to determine which treatment is optimal for a specific patient.

Purpose: To evaluate the efficiency of a novel device coupled with ultrassound for renal percutaneous puncture. Materials and Methods: After establishing hydronephrosis, ten pigs had three calyxes of each kidney punctured by the same urology resident, with and without the new device ("Punctiometer"). Time for procedure completion, number of attempts to reach the calyx, puncture precision and puncture complications were recorded in both groups and compared. Results: Puncture success on the first attempt was achieved in 25 punctures (83%) with the Punctiometer and in 13 punctures (43%) without the Punctiometer (p=0.011). The mean time required to perform three punctures in each kidney was 14.5 minutes with the Punctiometer and 22.4 minutes without the Punctiometer (p=0.025). The only complications noted were renal hematomas. In the Punctiometer group, all kidneys had small hematomas. In the no Punctiometer group 80% had small hematomas, 10% had a medium hematoma and 10% had a big hematoma. There was no difference in complications between both groups. Conclusions: The Punctiometer is an effective device to increase the likelihood of an accurate renal calyx puncture during PCNL, with a shorter time required to perform the procedure.

To avoid hormonal replacement after partial adrenalectomy (PA), establishing the precise limit of an adrenal gland resection is essential. Herein, we evaluated the use of three-dimensional (3D) adrenal gland printing and volumetry measurement before PA to improve the determination of the remnant gland volume.Concomitant total adrenalectomy and a contralateral PA were performed in a patient with primary macronodular adrenal hyperplasia that exhibited mild hypercortisolism, arterial hypertension, and diabetes. Before surgery, a 3D replica of the adrenal gland to be partially resected was printed and given to the surgeon. The volumetry of the gland was measured by computed tomography 3D image reconstruction.No postoperative complications were noted. Immediately after the surgery, the patient initiated corticosteroid replacement, which was interrupted 52 days later. At the 6-month follow-up, the patient stopped using medications for diabetes and reduced the number of antihypertensive medications from 5 to 1. The pre- and postoperative serum cortisol levels were, respectively, 28 and 8.7 mcg/dl (n 5-25 mcg/dl). The pre- and postoperative adrenocorticotropic hormone levels were, respectively,5 and 88 pg/ml (n 7.2-63 pg/ml). The postoperative adrenal volume was 12% of the total preoperative adrenal volume.The use of 3D printing associated with adrenal volumetry might be a useful tool for the surgeon when performing PA, enabling an estimation of the remnant gland volume.

Objective: Minimal invasive thermal ablative techniques are emerging as a viable option for patients who are not candidates for open, laparoscopic or robotic-assisted partial nephrectomy. Cryoablation is a low risk alternative with good oncologic outcomes. We present our initial experience with cryoablation for small renal masses using the laparoscopic approach. Patients and Methods: We prospectively collected the perioperative data of patients undergone renal cryoablation at our institution. From May/2009 to January/2011, 41 patients with incidental small renal mass were submitted to laparoscopic cryoablation. Results: The mean patient age was 58.8 years. The mean operative time was 115.4 ± 60.3 min and no patient needed blood transfusion. The mean of size tumors was 2.8 cm (1-5 cm). Intraoperative biopsies showed 27 (65%) malignant tumors, 5 (12%) oncocytomas, two (6%) angiomyolipomas 7 (17%) inconclusive. With a mean follow-up of 16 months (12-21), there were no significant differences between creatinine, estimated glomerular filtration rate and hemoglobin level before and after the procedure. There was no open conversion, kidney loss, urinary fistula, dialysis requirement or re-operations. Conclusion: Laparoscopic renal cryoablation is safe, with low complication rate and short learning curve.

PURPOSE: Metastatic renal cell carcinoma (RCC) is one of the most treatment-resistant malignancies and nephrectomy, isolated or combined with systemic chemotherapy typically has limited or no effectiveness. We report our initial results in patients treated with the association of molecular targeted therapy, nephrectomy, and hybrid dendritic-tumor cell (DC) vaccine. MATERIALS AND METHODS: Two male patients diagnosed with metastatic RCC were selected for the study. They were treated with the triple strategy, in which sunitinib (50 mg per day) was given for 4 weeks, followed by radical nephrectomy after two weeks. DC vaccine was initiated immediately after surgery and repeated monthly. Sunitinib was restarted daily after 2 to 3 weeks of surgery with a 7-day interval every 4 weeks. RESULTS: Both patients had complete adherence to the proposed treatment with DC vaccine therapy combined with sunitinib. Follow-up in these patients at 9 and 10 months demonstrated a stable disease in both, as shown by imaging and clinical findings, with no further treatment required. CONCLUSION: The immune response obtained with DC vaccine combined with the antiangiogenic effect of sunitinib and the potential benefits of cytoreductive nephrectomy in advanced disease could represent a new option in the treatment of metastatic RCC. Further prospective trials are needed not only to elucidate the ideal dosing and schedule, but also to better define the proof-of-concept proposed in this report and its role in clinical practice.

Purpose: To evaluate the presentation and early surgical outcomes of elderly patients undergoing adrenalectomy for phaeochromocytoma. Patients and Methods: A retrospective search was performed of our adrenal disorders database for patients who underwent surgery for phaeochromocytoma or paraganglioma between 2009 and 2014. Patients >60 years old were classified as elderly. The clinical manifestations, intraoperative course, and early postoperative outcomes of elderly patients were compared to those of younger individuals (