Primary Pheochromocytoma Research Articles

Comparison of the Sensitivity of 68 Ga-DOTATATE PET/CT with Other Imaging Modalities in Detecting Head and Neck Paraganglioma: Experience from Western India.

Background This study aimed to compare the sensitivity of 68 Ga-DOTATATE positron emission tomography/computed tomography (PET/CT) with other imaging modalities in the detection of head and neck paraganglioma (HNPGL). Methods The data of consecutive HNPGL patients ( n = 34) who had undergone at least 68 Ga-DOTATATE PET/CT and anatomical imaging (contrast-enhanced computed tomography/magnetic resonance imaging [CECT/MRI]) were retrospectively reviewed. The diagnosis of HNPGL (the primary tumor) was confirmed either by histopathology ( n = 10) or was based on clinical follow-up and correlation of anatomical with functional imaging in whom histopathology was not available ( n = 24). The sensitivities of 68 Ga DOTATATE PET/CT, 18F-fluorodeoxyglucose positron emission tomography/computed tomography ( 18 F-FDG-PET/CT), 131 I-metaiodobenzylguanidine ( 131 I-MIBG) scintigraphy, and CECT/MRI for primary HNPGL, associated primary pheochromocytoma + sympathetic paraganglioma (PCC + sPGL), and metastatic lesions were analyzed. Results Thirty-four patients (males: 15) [isolated HNPGL: 26, HNPGL + PCC: 04, HNPGL+ sPGL: 03, HNPGL + PCC + sPGL: 01] harboring 50 primary lesions were included. For total lesions, 68 Ga-DOTATATE PET/CT (99.3%) had significantly higher lesion-wise sensitivity than 18 F-FDG PET/CT (81.6%, p = 0.0164), 131 I-MIBG (15.2%, p ≤0.0001), CECT (46.3%, p ≤ 0.0001) but similar sensitivity as MRI neck (97%, p = 0.79). On head-to-head comparison (21 primary HNPGL and 39 metastatic lesions), 68 Ga DOTATATE PET/CT had significantly higher lesion-wise sensitivities for the detection of metastatic (100 vs. 71.9%, p = 0.04) and total lesions (100 vs. 77.2%, p ≤ 0.0001). Conclusion 68 Ga-DOTATATE PET/CT was the most sensitive imaging modality for the detection of HNPGL and related lesions with significantly higher lesion-wise sensitivities than those of 18 F-FDG PET/CT, 131 I-MIBG, and CECT.

Quantitative analysis of 68Ga-DOTA(0)-Tyr(3)-octreotate positron emission tomography/computed tomography imaging for the differential diagnosis of primary pheochromocytoma and paraganglioma.

Pheochromocytomas/paragangliomas (PPGLs) predominantly express somatostatin receptors (SSTRs) 2 and 3. 68Ga-DOTA(0)-Tyr(3)-octreotate (68Ga-DOTA-TATE) is an imaging radiopharmaceutical that selectively targets SSTR 2 with high affinity. The purpose of this study was to evaluate the utility of 68Ga-DOTA-TATE in the differential diagnosis of suspected PPGLs, and determine the optimal threshold for differential diagnoses. This retrospective study reviewed consecutive patients referred to the Chinese PLA General Hospital, Beijing between April 2018 and December 2020 who underwent both biochemical testing for catecholamine and 68Ga-DOTA-TATE positron emission tomography/computed tomography (PET/CT) for suspected PPGLs, without prior history. Patients with pathologic confirmation were selected for analysis. The following values were obtained for a quantitative analysis of 68Ga-DOTA-TATE imaging: maximal standardized uptake value (SUVmax), the ratio between the SUVmax of the lesion and the mean SUV (SUVmean) of the liver (SUVR), and the Krenning score (KS) of the lesion. According to their location, tumors were grouped as adrenal or extra-adrenal. Receiver operating characteristic (ROC) curves of the SUVR and KS were determined, and their diagnostic performance was calculated using general and subgroup-specific optimal thresholds. Concordance between the SUVR and KS was analyzed using a McNemar test. A total of 38 patients with PPGLs and 21 with non-PPGLs tumors were included in the final analysis. When a general optimal threshold for adrenal tumors was applied in pheochromocytoma (PCC) diagnosis, the sensitivity, specificity, and accuracy of the SUVR and KS were 86.4% (19/22) and 90.9% (20/22), 92.9% (13/14) and 78.6% (11/14), and 88.9% (32/36) and 86.1% (31/36), respectively. The SUVR and KS diagnostic results showed no differences in paraganglioma (PGL) diagnosis, with a sensitivity, specificity, and accuracy of 43.8% (7/16), 100.0% (7/7), and 60.9% (14/23), respectively. Using PPGL-specific optimal thresholds improved the diagnostic accuracy for extra-adrenal tumors. The diagnostic results of the SUVR and KS showed high concordance in both general and subgroup analyses. When PPGL-specific optimal thresholds were used, 68Ga-DOTA-TATE PET/CT correctly diagnosed 1 PCC with negative biochemical test results, and 5 PCCs and 1 PGL with borderline biochemical test results. Applying PPGL-specific thresholds of 68Ga-DOTA-TATE in diagnosing adrenal and extra-adrenal tumors is recommended for the differential diagnosis of PPGLs. When biochemical tests are negative or borderline, 68Ga-DOTA-TATE PET/CT should be included in the diagnostic procedure. The visual KS method has almost the same diagnostic efficiency as the quantitative SUVR method and has potential for recommendation in 68Ga-DOTA-TATE image analysis.

Prognosis of Malignant Pheochromocytoma and Paraganglioma (MAPP-Prono Study): A European Network for the Study of Adrenal Tumors Retrospective Study

Malignant pheochromocytoma and paraganglioma (MPP) are characterized by prognostic heterogeneity. Our objective was to look for prognostic parameters of overall survival (OS) in MPP patients. Retrospective multicenter study of MPP characterized by a neck-thoraco-abdomino-pelvic CT or MRI at the time of malignancy diagnosis in European centers between 1998 and 2010. One hundred sixty-nine patients from 18 European centers were included. Main characteristics of patients with MPP were: primary pheochromocytoma in 53% of patients; tumor- or hormone-related symptoms in 57% or 58% of cases; positive plasma or urine hormones in 81% of patients; identification of a mutation in SDHB in 42% of cases. Metastatic sites included bone (64%), lymph node (40%), lung (29%), and liver (26%); mean time between initial and malignancy diagnosis was 43 months (range, 0 to 614). Median follow-up was 68 months and median survival 6.7 years. Using univariate analysis, better survival was associated with head and neck paraganglioma, age <40 years, metanephrines less than fivefold the upper limits of the normal range, and low proliferative index. In multivariate analysis, hypersecretion [hazard ratio 3.02 (1.65 to 5.55); P = 0.0004] was identified as an independent significant prognostic factor of worst OS. Our results do not confirm SDHB mutations as a major prognostic parameter in MPP and suggest additional key molecular events involved in MPP tumor progression. Aside from SDHB mutation, the biology of aggressive MPP remains to be understood.

Clinical Presentation, Diagnosis, and Management of Primary Aldosteronism and Pheochromocytoma

Clinical Presentation, Diagnosis, and Management of Primary Aldosteronism and Pheochromocytoma

ARHI is a novel epigenetic silenced tumor suppressor in sporadic pheochromocytoma.

Pheochromocytoma (PCC) is related to germline mutations in 12 susceptibility genes. Although comparative genomic hybridization array has revealed some putative tumor suppressor genes on the short arm of chromosome 1 that are likely to be involved in PCC tumorigenesis, the molecules involved, except for those encoded by known susceptibility genes, have not been found in the generation of sporadic tumors. In the present work, we first identified that the unmethylated allele of Aplasia Ras homolog member I (ARHI) was deleted in most PCC tumors which retained a hypermethylated copy, while its mRNA level was significantly correlated with the unmethylated copy. De-methylation experiments confirmed that expression of ARHI was also regulated by the methylation level of the remaining allele. Furthermore, ARHI overexpression inhibited cell proliferation, with cell cycle arrest and induction of apoptosis, in ARHI-negative primary human PCC cells, whereas knockdown of ARHI demonstrated the opposite effect in ARHI-positive primary human PCC cells. Finally, we demonstrated that ARHI has the ability to suppress pAKT and pErK1/2, to promote the expression of p21Waf1/Cip1 and p27Kip1, and also to increase p27Kip1 protein stability. In summary, ARHI was silenced or downregulated in PCC tissues harboring only one hypermethylated allele. ARHI contributes to tumor suppression through inhibition of PI3K/AKT and MAKP/ERK pathways, to upregulate cell cycle inhibitors such as p27Kip1. We therefore reasoned that ARHI is a novel epigenetic silenced tumor suppressor gene on chromosome 1p that is involved in sporadic PCC tumorigenesis.

Genetic aspects of primary hyperaldosteronism and pheochromocytoma

Pheochromocytoma and primary hyperaldosteronism are the most common causes of secondary hypertension. In a group of patients with primary hyperaldosteronism the prevalence of somatic mutation has been established in patients with aldosterone-producing adenomas (APA), genetic mutations have been identified in patients with familytypes of the disease. The authors declare that aldosterone-producing cellular clusters, which derived from zona glomerulosa, appear as a result of somatic mutations and might be a precursor of APA. Development of bilateral adrenal hyperplasia and APA might be explained by an existence of autoantibodies and their chronic stimulation of zona glomerulosa. The assessment of somatic and germline mutations in patients with pheochromocytoma and paraganglioma facilitates early diagnostics other tumors within syndromic neoplasia. Implementation of new genetic test in practice would improve early diagnosis of adrenal pathology in hypertensive patients.

Malignant hypertension in primary and recurrent pheochromocytoma

Malignant hypertension in primary and recurrent pheochromocytoma

Adrenal Neoplasia

The adrenal glands are composed of two distinct tissue types: the cortex, which serves as a factory for adrenal steroidogenesis, and the medulla, which produces catecholamines as a neuroendocrine organ. Neoplasia of the adrenal is approached by considering both whether the tumor is benign or malignant and whether it may represent a hormonally active tumor that can contribute to cardiometabolic disease or a hormonally silent tumor. Adrenal neoplasia is rarely malignant. This module discusses the approach to an incidentally discovered adrenal mass, with emphasis on the clinical determination as to whether it is benign or malignant and hormonally functional or nonfunctional. The pathogenesis and genetics of hyperaldosteronism and pheochromocytoma-paraganglioma are reviewed, as are the pathogenesis and management of adrenocortical carcinoma. Tables describe the differential diagnosis and diagnostic approach for an incidentally discovered adrenal mass; suggested biochemical screening tests for incidentally discovered adrenal masses; radiographic features of adrenal masses to determine benign or malignant potential; and the genetics of primary hyperaldosteronism, pheochromocytoma, and paraganglioma syndromes. A drawing shows the genetic mechanisms of hyperaldosteronism in familial hyperaldosteronism type III. Algorithms outline the suggested management approach for the incidentally discovered adrenal mass, genetic counseling and testing for patients with pheochromocytoma or paraganglioma, testing for family members of patients with pheochromocytoma and positive genetic testing, patients with stage I–III adrenocortical carcinoma, and patients with advanced adrenocortical carcinoma. This module contains 6 highly rendered figures, 6 tables, 55 references, and 5 MCQs.

Very late recurrence of an apparently benign pheochromocytoma

Pheochromocytoma is a tumor that has the probability to relapse in about 10% of surgically treated cases. Currently, the only recognized criteria of malignancy in these neoplasms are the evidence of metastasis at non-chromaffin sites. No reliable clinical or histopathological parameter has been, so far, identified to predict malignancy in patients with diagnosis of primary pheochromocytoma. Several authors has attempted to propose morphologic features to detect potentially malignant pheochromocytomas, but there are still too many reported cases of recurrence, also after decades, in tumors that, according to the current knowledge, are considered "benign". Here we report a case of recurrence, after 25 years, of a pheochromocytoma that had not enough criteria to be considered as malignant.

Progenitor Cell Line (hPheo1) Derived from a Human Pheochromocytoma Tumor

BackgroundPheochromocytomas are rare tumors generally arising in the medullary region of the adrenal gland. These tumors release excessive epinephrine and norepinephrine resulting in hypertension and cardiovascular crises for which surgery is the only definitive treatment. Molecular mechanisms that control tumor development and hormone production are poorly understood, and progress has been hampered by the lack of human cellular model systems. To study pheochromocytomas, we developed a stable progenitor pheochromocytoma cell line derived from a primary human tumor.MethodsAfter IRB approval and written informed consent, human pheochromocytoma tissue was excised, minced, dispersed enzymatically, and cultured in vitro. Primary pheochromocytoma cells were infected with a lentivirus vector carrying the catalytic subunit of human telomerase reverse transcriptase (hTERT). The hTERT immortalized cells (hPheo1) have been passaged >300 population doublings. The resulting cell line was characterized morphologically, biochemically and for expression of neuroendocrine properties. The expression of marker enzymes and proteins was assessed by immunofluorescence staining and immunoblotting. Telomerase activity was determined by using the telomeric repeat amplification protocol (TRAP) assay.ResultsWe have established a human pheochromocytoma precursor cell line that expresses the neuroendocrine marker, chromogranin A, when differentiated in the presence of bone morphogenic protein 4 (BMP4), nerve growth factor (NGF), and dexamethasone. Phenylethanolamine N-methyltransferase (PNMT) expression is also detected with this differentiation regimen. CD-56 (also known as NCAM, neural cell adhesion molecule) is expressed in these cells, but CD31 (also known as PECAM-1, a marker of endothelial cells) is negative.ConclusionsWe have maintained hTERT-immortalized progenitor cells derived from a pheochromocytoma (hPheo1) in culture for over 300 population doublings. This progenitor human cell line is normal diploid except for a deletion in the p16 region and has inducible neuroendocrine biomarkers. These cells should be a valuable reagent for studying mechanisms of tumor development and for testing novel therapeutic approaches.

Targeting Heat Shock Protein 90 for the Treatment of Malignant Pheochromocytoma

Metastatic pheochromocytoma represents one of the major clinical challenges in the field of neuroendocrine oncology. Recent molecular characterization of pheochromocytoma suggests new treatment options with targeted therapies. In this study we investigated the 90 kDa heat shock protein (Hsp90) as a potential therapeutic target for advanced pheochromocytoma. Both the first generation, natural product Hsp90 inhibitor 17-allylamino-17-demethoxygeldanamycin (17-AAG, tanespimycin), and the second-generation synthetic Hsp90 inhibitor STA-9090 (ganetespib) demonstrated potent inhibition of proliferation and migration of pheochromocytoma cell lines and induced degradation of key Hsp90 clients. Furthermore, ganetespib induced dose-dependent cytotoxicity in primary pheochromocytoma cells. Using metastatic models of pheochromocytoma, we demonstrate the efficacy of 17-AAG and ganetespib in reducing metastatic burden and increasing survival. Levels of Hsp70 in plasma from the xenograft studies served as a proximal biomarker of drug treatment. Our study suggests that targeting Hsp90 may benefit patients with advanced pheochromocytoma.

Genetic alterations of RDINK4/ARF enhancer in human cancer cells

Recent identification of an enhancer element, RD(INK4/ARF) (RD), in the prominent INK4/ARF locus provides a novel mechanism to simultaneously regulate the transcription of p15(INK4B) (p15), p14(ARF) , and p16(INK4A) (p16) tumor suppressor genes. While genetic inactivation of p15, p14(ARF) , and p16 in human tumors has been extensively studied, little is known about genetic alterations of RD and its impact on p15, p14(ARF) , and p16 in human cancer. The purpose of this study was to investigate the potential existence of genetic alterations of RD in human cancer cells. DNAs extracted from 17 different cancer cell lines and 31 primary pheochromocytoma tumors were analyzed for deletion and mutation of RD using real-time PCR and direct DNA sequencing. We found that RD was deleted in human cancer cell lines and pheochromocytoma tumors at frequencies of 41.2% (7/17) and 13.0% (4/31), respectively. While some of these RD deletion events occurred along with deletions of the entire INK4/ARF locus, other RD deletion events were independent of genetic alterations in p15, p14(ARF) , and p16. Furthermore, the status of RD was poorly associated with the expression of p15, p14(ARF) , and p16 in tested cancer cell lines and tumors. This study demonstrates for the first time that deletion of the RD enhancer is a prevalent event in human cancer cells. Its implication in carcinogenesis remains to be further explored.

Immunohistochemical Evidence of Dysregulation of the Mammalian Target of Rapamycin Pathway in Primary and Metastatic Pheochromocytomas

To characterize the status of the mammalian target of rapamycin pathway using formalin-fixed, paraffin-embedded specimens from patients with primary and metastatic pheochromocytoma. Tissue microarrays were built from 19 normal adrenal medullas, 39 primary pheochromocytomas, and 8 unrelated metastatic pheochromocytomas. In 2 of the 8 cases of metastatic pheochromocytoma tissues, samples from the primary tumor were available. The expression levels of phosphatase and tensin homolog, phosphorylated Akt, phosphorylated S6, p27, and c-myc were evaluated by immunohistochemistry. The levels of phosphatase and tensin homolog and p27 were greater in the nontumor tissue than in the primary and metastatic pheochromocytomas. Increasing levels of phosphorylated Akt were noted in the nontumor adrenal medulla, primary pheochromocytomas, and metastatic pheochromocytomas. Finally, the levels of phosphorylated S6 were greater in the metastatic pheochromocytomas than in the nontumor adrenal medulla and primary pheochromocytomas. We found evidence of dysregulation of the mammalian target of rapamycin pathway in primary and metastatic pheochromocytomas, with increased phosphorylated S6 and phosphorylated Akt, and decreased phosphatase and tensin homolog and p27 expression levels. Because the currently available treatment modalities are less than optimal, our findings lend additional support to continuing to explore the utility of mammalian target of rapamycin pathway-targeted therapy for pheochromocytomas.

Secretin Receptor Promotes the Proliferation of Endocrine Tumor Cells Via the PI3K/AKT Pathway

The secretin receptor (SR), a G protein-coupled receptor, mediates the effects of the gastrointestinal hormone secretin on digestion and water homeostasis. Recently, high SR expression has been observed in pancreatic ductal adenocarcinomas, cholangiocellular carcinomas, gastrinomas, and bronchopulmonary carcinoid tumors. Receptor overexpression associates with enhanced secretin-mediated signaling, but whether this molecule plays an independent role in tumorigenesis is currently unknown. We recently discovered that pheochromocytomas developing in rats affected by the MENX (multiple endocrine neoplasia-like) syndrome express at very high-level Sctr, encoding SR. We here report that SR are also highly abundant on the membranes of rat adrenal and extraadrenal pheochromocytoma, starting from early stages of tumor development, and are functional. PC12 cells, the best characterized in vitro pheochromocytoma model, also express Sctr at high level. Thus, we used them as model to study the role of SR in neoplastic transformation. Small interfering RNA-mediated knockdown of Sctr decreases PC12 cells proliferation and increases p27 levels. The proproliferative effect of SR in PC12 cells is mediated, in part, by the phosphatidylinositol 3 kinase (PI3K)/serine-threonine protein kinase (AKT) pathway. Transfection of Sctr in Y1 adrenocortical carcinoma cells, expressing low endogenous levels of Sctr, stimulates cell proliferation also, in part, via the PI3K/AKT signaling cascade. Because of the link between SR and PI3K/AKT signaling, tumor cells expressing high levels of the receptor (MENX-associated primary pheochromocytoma and NCI-H727 human bronchopulmonary carcinoid cells) respond well and in a SR-dependent manner to PI3K inhibitors, such as NVP-BEZ235. The association between SR levels and response to PI3K inhibition might open new avenues for the treatment of tumors overexpressing this receptor.

Primary cardiac pheochromocytoma with Multiple Endocrine Neoplasia

Cardiac pheochromocytoma with multiple endocrine neoplasia syndrome (MENS) is rare. We present a rare case of concurrent cardiac pheochromocytoma and pituitary adenoma, a rare variant of the MEN syndromes and a review of the literature with special emphasis on diagnosis and treatment. Different from the single MENS type I or type II, Variant MENS' symptoms and signs are so nontypical that it is easy to make a misdiagnosis or missed diagnosis. One patient with variant MENS was treated surgically and relevant case data were collected. The perioperative course was uneventful. At 24-month follow-up, catecholamine levels returned to normal and no symptoms of pheochromocytoma was found. Cardiac pheochromocytoma with Multiple Endocrine Neoplasia can be treated by operation with good prognosis. Surgical removal to provide relief or effective control of symptoms is the treatment of choice.

Metastatic pheochromocytoma: Does the size and age matter?

Pheochromocytomas are tumours arising from chromaffin tissue located in the adrenal medulla associated with typical symptoms and signs which may occasionally develop metastases, which are defined as the presence of tumour cells at sites where these cells are not found. This retrospective analysis was focused on clinical, genetic and histopathologic characteristics of primary metastatic versus primary benign pheochromocytomas. We identified 41 subjects with metastatic pheochromocytoma and 108 subjects with apparently benign pheochromocytoma. We assessed dimension and biochemical profile of the primary tumour, age at presentation and time to develop metastases. Subjects with metastatic pheochromocytoma presented at a significantly younger age (41·4 ± 14·7 vs. 50·2 ± 13·7 years; P < 0·001) with larger primary tumours (8·38 ± 3·27 vs. 6·18 ± 2·75 cm; P < 0·001) and secreted more frequently norepinephrine (95·1% vs. 83·3%; P = 0·046) compared to subjects with apparently benign pheochromocytomas. No significant differences were found in the incidence of genetic mutations in both groups of subjects (25·7% in the metastatic group and 14·7% in the benign group; P = 0·13). From available histopathologic markers of potential malignancy, only necrosis occurred more frequently in subjects with metastatic pheochromocytoma (27·6% vs. 0%; P < 0·001). The median time to develop metastases was 3·6 years with the longest interval 24 years. In conclusion, regardless of a genetic background, the size of a primary pheochromocytoma and age of its first presentation are two independent risk factors associated with the development of metastatic disease.

Outpatient Evaluation of Secondary Causes of Resistant Hypertension

Primary aldosteronism, pheochromocytoma and renovascular hypertension are hypertensive syndromes often associated with resistant hypertension. Early recognition of these disorders has come as the result of a better understanding of their pathophysiology. Prompt and definitive diagnosis has resulted from the availability of sensitive and accurate diagnostic tools. Finally, safe and effective pharmacotherapeutic agents and innovative surgical techniques have led to excellent and predictable clinical outcomes.

Mediastinal Pheochromocytoma with Single Coronary Blood Supply: A Case Report

Primary pheochromocytomas located outside the adrenal glands account for only 10% of all pheochromocytomas. Mediastinal pheochromocytomas are even rarer and usually represent a therapeutic challenge as they often infiltrate adjacent structures. We report the case of a large primary mediastinal pheochromocytoma in a 65-year-old patient presenting with a sudden angina-like chest pain and dyspnea. Thoracic multislice computed tomography showed an 8 x 5 x 6-cm retrocardiac mass causing compression of both atria and infiltrating the left superior pulmonary vein. The tumor was highly vascularized and presented a blood supply derived from the circumflex artery. The mass was successfully removed by open heart surgery, and the patient was discharged 10 days postoperatively.

Cardiac Pheochromocytomas Detected by Tc-99m-Hydrazinonicotinyl-Tyr3-Octreotide (HYNIC-TOC) Scintigraphy

Primary pheochromocytomas of the heart are extremely rare tumors and difficult to diagnose. Iodine labeled metaiodobenzylguanidine (MIBG) is the first choice of the nuclear medicine modality in the evaluation of adrenal pheochromocytoma. However, the sensitivity of MIBG in the diagnosis of extraadrenal pheochromocytoma is less optimal. In this preliminary report, the efficacy of octreotide scintigraphy using Tc-99m labeled hydrazinonicotinyl-Tyr3-octreotide (HYNIC-TOC) in the evaluation of primary cardiac pheochromocytoma was assessed.

Endoscopic ultrasound-guided fine-needle aspiration of left adrenal gland masses

Although the left adrenal gland is readily visible by endoscopic ultrasound (EUS), there are few published data on the utility of EUS-guided fine-needle aspiration (EUS-FNA) of this site. The aim of this study was to report our experience of EUS-FNA of left adrenal gland masses. In this retrospective case series, we reviewed our EUS and cytology databases to identify consecutive patients who underwent EUS-FNA of the left adrenal gland between January 1997 and January 2004. Medical records were reviewed and the results of EUS examinations and cytological investigations were abstracted. Our searches resulted in the identification of a series of 38 consecutive patients who underwent EUS for the evaluation of a lung mass (n = 14), a pancreatic mass (n = 14), obstructive jaundice (n = 1), dysphagia (n = 2), an ampullary adenoma (n = 1), celiac block (n = 1), or a left adrenal gland mass (n = 5). The mean maximal left adrenal mass diameter was 24 mm (range 7-66 mm). Diagnoses after EUS-FNA (the mean number of passes was 3.6) were: metastatic lung cancer (n = 2), esophageal adenocarcinoma (n = 1), melanoma (n = 1), renal cell carcinoma (n = 1), and pancreatic neuroendocrine tumor (n = 1); primary pheochromocytoma (n = 1); benign adrenal tissue (n = 21); and granulomatous inflammation (n = 1). Nine aspirations (24 %) were nondiagnostic. The absence of a discrete adrenal mass on EUS occurred more frequently in patients with nondiagnostic biopsies than in those with diagnostic biopsies (56 % vs. 7 %; odds ratio 23.4, 95 %CI 3.5 - 157.0; P = 0.004). No complications were noted. EUS-FNA of the left adrenal gland is safe and can be useful for the evaluation and staging of suspected malignancy. Nondiagnostic biopsies are more common when sampling diffusely enlarged glands, compared with glands with a focal mass.