Multiple Pheochromocytomas Research Articles

PD03-03 CHARACTERIZATION OF THE PHEOCHROMOCYTOMA-PREDOMINANT SUBGROUP OF VON HIPPEL-LINDAU DISEASE

You have accessJournal of UrologyCME1 Apr 2023PD03-03 CHARACTERIZATION OF THE PHEOCHROMOCYTOMA-PREDOMINANT SUBGROUP OF VON HIPPEL-LINDAU DISEASE Julie Solomon, Keith Lawson, Lauren Loebach, Christopher Ricketts, W. Marston Linehan, and Mark Ball Julie SolomonJulie Solomon More articles by this author , Keith LawsonKeith Lawson More articles by this author , Lauren LoebachLauren Loebach More articles by this author , Christopher RickettsChristopher Ricketts More articles by this author , W. Marston LinehanW. Marston Linehan More articles by this author , and Mark BallMark Ball More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003220.03AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Von Hippel-Lindau (VHL) disease is a heterogenous hereditary tumor syndrome affecting multiple organs. A subset of VHL patients present predominantly with pheochromocytomas. We developed a novel classification system to define pheochromocytoma-predominant (PP) VHL disease. METHODS: VHL patients who underwent adrenalectomy with pathology-proven pheochromocytoma at our institution were included. We defined PP VHL a priori as patients with one or more of the following traits: early onset [age at first pheochromocytoma below the cohort’s median age (28.2 years)], family history of pheochromocytomas, multiple pheochromocytomas, and ectopic pheochromocytoma(s). PP VHL was compared to non-PP (NPP) VHL for differences in genotype and phenotype. RESULTS: One-hundred thirty-nine VHL patients (56.1% male, 90.6% white) were examined. Preliminary analysis showed that three characteristics (early onset, family history, and multiple pheochromocytomas) correlated with each other (Table 1). Ectopic pheochromocytoma(s) did not correlate with two factors, so it was excluded from the definition of PP VHL. One-hundred twelve (80.6%) of our patients met the final definition. Further analysis demonstrated that PP VHL patients had significantly different phenotypes and genotypes than NPP VHL patients (Table 2). PP VHL patients were less likely to have most additional tumor types, including renal cell carcinoma (RCC) (p<0.01) and more likely to have missense mutations (p<0.01). Furthermore, PP VHL patients were most likely to have 0 or 1 extra-adrenal tumors while NPP VHL patients were most likely to have 4 or 5 (Figure 1). CONCLUSIONS: PP VHL patients are phenotypically distinct from their NPP counterparts and are significantly less likely to have more than one other VHL manifestation, including RCC. Source of Funding: Supported by the National Institutes of Health (NIH) Intramural Research Program, and the NIH Medical Research Scholars Program, a public–private partnership supported jointly by the NIH and contributions to the Foundation for the NIH from the Doris Duke Charitable Foundation, The American Association for Dental Research, the Colgate-Palmolive Company, and other private donors © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e75 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Julie Solomon More articles by this author Keith Lawson More articles by this author Lauren Loebach More articles by this author Christopher Ricketts More articles by this author W. Marston Linehan More articles by this author Mark Ball More articles by this author Expand All Advertisement PDF downloadLoading ...

Co-occurrence of mutations in NF1 and other susceptibility genes in pheochromocytoma and paraganglioma.

The percentage of patients diagnosed with pheochromocytoma and paraganglioma (altogether PPGL) carrying known germline mutations in one of the over fifteen susceptibility genes identified to date has dramatically increased during the last two decades, accounting for up to 35-40% of PPGL patients. Moreover, the application of NGS to the diagnosis of PPGL detects unexpected co-occurrences of pathogenic allelic variants in different susceptibility genes. Herein we uncover several cases with dual mutations in NF1 and other PPGL genes by targeted sequencing. We studied the molecular characteristics of the tumours with co-occurrent mutations, using omic tools to gain insight into the role of these events in tumour development. Amongst 23 patients carrying germline NF1 mutations, targeted sequencing revealed additional pathogenic germline variants in DLST (n=1) and MDH2 (n=2), and two somatic mutations in H3-3A and PRKAR1A. Three additional patients, with somatic mutations in NF1 were found carrying germline pathogenic mutations in SDHB or DLST, and a somatic truncating mutation in ATRX. Two of the cases with dual germline mutations showed multiple pheochromocytomas or extra-adrenal paragangliomas - an extremely rare clinical finding in NF1 patients. Transcriptional and methylation profiling and metabolite assessment showed an "intermediate signature" to suggest that both variants had a pathological role in tumour development. In conclusion, mutations affecting genes involved in different pathways (pseudohypoxic and receptor tyrosine kinase signalling) co-occurring in the same patient could provide a selective advantage for the development of PPGL, and explain the variable expressivity and incomplete penetrance observed in some patients.

Recurrent Germline DLST Mutations in Individuals with Multiple Pheochromocytomas and Paragangliomas

Pheochromocytomas and paragangliomas (PPGLs) provide some of the clearest genetic evidence for the critical role of metabolism in the tumorigenesis process. Approximately 40% of PPGLs are caused by driver germline mutations in 16 known susceptibility genes, and approximately half of these genes encode members of the tricarboxylic acid (TCA) cycle. Taking as a starting point the involvement of the TCA cycle in PPGL development, we aimed to identify unreported mutations that occurred in genes involved in this key metabolic pathway and that could explain the phenotypes of additional individuals who lack mutations in known susceptibility genes. To accomplish this, we applied a targeted sequencing of 37 TCA-cycle-related genes to DNA from 104 PPGL-affected individuals with no mutations in the major known predisposing genes. We also performed omics-based analyses, TCA-related metabolite determination, and13C5-glutamate labeling assays. We identified five germline variants affecting DLST in eight unrelated individuals (∼7%); all except one were diagnosed with multiple PPGLs. A recurrent variant, c.1121G>A (p.Gly374Glu), found in four of the eight individuals triggered accumulation of 2-hydroxyglutarate, both in tumors and in a heterologous cell-based assay designed to functionally evaluate DLST variants. p.Gly374Glu-DLST tumors exhibited loss of heterozygosity, and their methylation and expression profiles are similar to those of EPAS1-mutated PPGLs; this similarity suggests a link between DLST disruption and pseudohypoxia. Moreover, we found positive DLST immunostaining exclusively in tumors carrying TCA-cycle or EPAS1 mutations. In summary, this study reveals DLST as a PPGL-susceptibility gene and further strengthens the relevance of the TCA cycle in PPGL development.

Heart combined with adrenal multiple pheochromocytomas

Pheochromocytoma is a kind of rare tumor, occurring at any site in the sympathoadrenal system. Main lesions occur within the adrenal gland; only 1%–2% occur within the chest, and most of these are located in the posterior mediastinum. Intrapericardial pheochromocytoma is extremely rare in clinic, only about 100 cases have been reported in total in both the domestic and foreignliterature since Besterman et al. first reported in 1974. It is often difficult to diagnose and locate these tumors. Hence, we present here a case of adrenal combined with heart multiple pheochromocytomas and discuss about techniques contributed to diagnosis and localization.

Targeted Exome Sequencing of Krebs Cycle Genes Reveals Candidate Cancer-Predisposing Mutations in Pheochromocytomas and Paragangliomas.

Purpose: Mutations in Krebs cycle genes are frequently found in patients with pheochromocytomas/paragangliomas. Disruption of SDH, FH or MDH2 enzymatic activities lead to accumulation of specific metabolites, which give rise to epigenetic changes in the genome that cause a characteristic hypermethylated phenotype. Tumors showing this phenotype, but no alterations in the known predisposing genes, could harbor mutations in other Krebs cycle genes.Experimental Design: We used downregulation and methylation of RBP1, as a marker of a hypermethylation phenotype, to select eleven pheochromocytomas and paragangliomas for targeted exome sequencing of a panel of Krebs cycle-related genes. Methylation profiling, metabolite assessment and additional analyses were also performed in selected cases.Results: One of the 11 tumors was found to carry a known cancer-predisposing somatic mutation in IDH1 A variant in GOT2, c.357A>T, found in a patient with multiple tumors, was associated with higher tumor mRNA and protein expression levels, increased GOT2 enzymatic activity in lymphoblastic cells, and altered metabolite ratios both in tumors and in GOT2 knockdown HeLa cells transfected with the variant. Array methylation-based analysis uncovered a somatic epigenetic mutation in SDHC in a patient with multiple pheochromocytomas and a gastrointestinal stromal tumor. Finally, a truncating germline IDH3B mutation was found in a patient with a single paraganglioma showing an altered α-ketoglutarate/isocitrate ratio.Conclusions: This study further attests to the relevance of the Krebs cycle in the development of PCC and PGL, and points to a potential role of other metabolic enzymes involved in metabolite exchange between mitochondria and cytosol. Clin Cancer Res; 23(20); 6315-24. ©2017 AACR.

Carotid Body Paraganglioma With an SDHD Gene Mutation: The Need For Genetic Testing

ABSTRACT Objective: To report a case of carotid body paraganglioma occurring in conjunction with a succinate dehydrogenase complex subunit D (SDHD) gene mutation with comorbidities of multiple retroperitoneal paragangliomas and pheochromocytoma. This case emphasizes the importance of performing genetic analyses in all cases of paragangliomas with carotid body involvement, multifocal origin, or concurrent pheochromocytoma to identify potential hereditary tumor susceptibility. We also emphasize the importance of familial screening of all first-degree family relatives of patients who test positive for germline mutations. Methods: A 30-year-old male underwent surgery to excise a carotid body tumor and multiple retroperitoneal masses and to perform a partial adrenalectomy. Results: Pathologic evaluation of carotid body and retroperitoneal specimens confirmed that they were histologically and immunohistochemically consistent with paragangliomas. The excised adrenal gland specimen tested positive for pheochromoc...

Abstract 3943: Genetic abnormalites in hypoxia sensing regulators cause human pheochromocytoma/paraganglioma and plolycythemia syndrome

Abstract Hypoxia inducible factors (HIFs) control the cellular response to hypoxia and when dysregulated, contribute to tumorigenesis. In the presence of oxygen, HIFs are strictly deactivated via EGLN/VHL/26S proteasome degradation mechanism. We identified that either gain-of-function mutations in HIF2A, or loss-of-function mutations in EGLN1/2, result in the multiple pheochromocytomas or paraganglioma associated with polycythemia. Mutation in HIF2A or EGLN1/2 cause compromised interaction of prolyl hydroxylase to HIF-α and lead to defects of HIF-α degradation. Stabilized HIF-α translocates into cell nucleus and function as a potent transcriptional factor, which induces constitutive transcriptional activation of hypoxia related genes, as well as pseudohypoxic change in cellular signaling and metabolism. Our finding provided direct evidence that genetic defect in intrinsic HIF-α and its regulatory proteins EGLN1/2 can be a key factor involved in the pathogenesis of this tumor-associated syndrome. Citation Format: Chunzhang Yang, Herui Wang, Karel Pacak, Zhengping Zhuang. Genetic abnormalites in hypoxia sensing regulators cause human pheochromocytoma/paraganglioma and plolycythemia syndrome. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3943. doi:10.1158/1538-7445.AM2015-3943

Perioperative, Functional, and Oncologic Outcomes of Partial Adrenalectomy for Multiple Ipsilateral Pheochromocytomas

Managing patients with multiple adrenal masses is technically challenging. We present our experience with minimally invasive partial adrenalectomy (PA) performed for synchronous multiple ipsilateral pheochromocytomas in a single setting. We reviewed records of patients undergoing PA for pheochromocytoma at the National Cancer Institute between 1994 and 2010. Patients were included if multiple tumors were excised from the ipsilateral adrenal gland in the same operative setting. Perioperative, functional, and oncologic outcomes of PA for multiple pheochromocytomas are shown. Of 121 partial adrenalectomies performed, 10 procedures performed in eight patients for synchronous multiple ipsilateral pheochromocytomas were identified. All eight patients were symptomatic at presentation. The mean patient age was 30.6 years, median follow up was 12 months. The average surgical time was 228 minutes, average blood loss of 125 mL, and average number of tumors removed was 2.6 per adrenal. In total, 26 tumors were removed, 24 were pathologically confirmed pheochromocytomas, while two were adrenal cortical hyperplasia. After surgery, all patients had resolution of their symptoms, one patient required steroid replacement postoperatively. On postoperative imaging, one patient had evidence of ipsilateral adrenal nodule at the prior resection site 2 months postoperatively, which was consistent with incomplete resection. Minimally invasive surgical resection of synchronous multiple pheochromocytomas is feasible with acceptable perioperative, functional, and short-term oncologic outcomes.

Graves′ disease allied with multiple pheochromocytoma

Pheochromocytoma is an uncommon cause of high blood pressure touching adults. The combination of severe hypertension in the triad of headache, sweating, and tachycardia should suggest this diagnosis; this clinical picture is similar to that of hyperthyroidism. We report the case of a 22-year-old patient with multiple pheochromocytoma associated with Graves’ disease revealed by malignant hypertension and discussed the difficulties of the diagnosis and the treatment approach.

29 PERIOPERATIVE, FUNCTIONAL AND ONCOLOGIC OUTCOMES OF PARTIAL ADRENALECTOMY FOR MULTIPLE IPSILATERAL PHEOCHROMOCYTOMA

You have accessJournal of UrologyAdrenal: Surgery/Tumors/Benign and Malignant Disease1 Apr 201129 PERIOPERATIVE, FUNCTIONAL AND ONCOLOGIC OUTCOMES OF PARTIAL ADRENALECTOMY FOR MULTIPLE IPSILATERAL PHEOCHROMOCYTOMA Gopal Gupta, Kelly Lin, W. Marston Linehan, Peter Pinto, and Gennady Bratslavsky Gopal GuptaGopal Gupta Bethesda, MD More articles by this author , Kelly LinKelly Lin Bethesda, MD More articles by this author , W. Marston LinehanW. Marston Linehan Bethesda, MD More articles by this author , Peter PintoPeter Pinto Bethesda, MD More articles by this author , and Gennady BratslavskyGennady Bratslavsky Bethesda, MD More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.091AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Partial adrenalectomy (PA) is gaining acceptance as a treatment option for patients with pheochromocytoma (pheo). As of today, there is no literature on PA performed for synchronous multiple ipsilateral pheos at a single setting. We report on the perioperative, functional, and oncologic outcomes of patients treated with PA for multiple adrenal pheos. METHODS We reviewed the records of all patients who underwent PA at the NCI from January of 1994 to November 2010. Demographic, perioperative, and pathologic data were collected. The functional outcomes were examined by resolution of symptoms, normalization of catecholamines, and the need for steroid replacement. Oncologic outcomes were assessed via review of the most recent imaging for the presence of persistent or recurrent disease. RESULTS Of 121 consecutive PA performed since 1994, we identified 10 procedures performed in 8 patients for multiple ipsilateral pheos. Six patients (75%) had known hereditary syndromes predisposing them to pheos. One patient underwent staged bilateral PA and a second patient underwent simultaneous bilateral PA. All cases for multiple adrenal pheos were performed using minimally-invasive approach (4 with conventional laparoscopy and 5 with robotic assistance). Average surgical time was 228 min (110–357) and EBL was 125 mL (50–300). There were no perioperative complications. An average of 2.6 (2–4) tumors was resected per gland with the average largest tumor size of 2.3 cm (0.8–5). Of the 26 tumors removed, 24 were pheochromocytoma and 2 were adrenal-cortical hyperplasia. At a median follow-up of 12 months (1.2–28) all patients had resolution of their symptoms and normalization of catecholamine levels. Among two patients treated with PA on a solitary adrenal gland, one required steroid replacement post-operatively after removal of 4 tumors. On postoperative imaging only one patient had evidence of an ipsilateral adrenal nodule consistent with incomplete resection 2 months post operatively. CONCLUSIONS PA for resection of multiple pheochromocytoma is safe, feasible, and provides patients with promising functional and oncologic outcomes at early follow up. The procedure can be performed utilizing a minimally invasive approach. Although local recurrence rates are low, longer follow up is needed to establish durable oncologic efficacy. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e11 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Gopal Gupta Bethesda, MD More articles by this author Kelly Lin Bethesda, MD More articles by this author W. Marston Linehan Bethesda, MD More articles by this author Peter Pinto Bethesda, MD More articles by this author Gennady Bratslavsky Bethesda, MD More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Clinical Predictors and Algorithm for the Genetic Diagnosis of Pheochromocytoma Patients

Six pheochromocytoma susceptibility genes causing distinct syndromes have been identified; approximately one of three of all pheochromocytoma patients carry a predisposing germline mutation. When four major genes (VHL, RET, SDHB, SDHD) are analyzed in a clinical laboratory, costs are approximately $3,400 per patient. The aim of the study is to systematically obtain a robust algorithm to identify who should be genetically tested, and to determine the order in which genes should be tested. DNA from 989 apparently nonsyndromic patients were scanned for germline mutations in the genes VHL, RET, SDHB, SDHC, and SDHD. Clinical parameters were analyzed as potential predictors for finding mutations by multiple logistic regression, validated by bootstrapping. Cost reduction was calculated between prioritized gene testing compared with that for all genes. Of 989 apparently nonsyndromic pheochromocytoma cases, 187 (19%) harbored germline mutations. Predictors for presence of mutation are age <45 years, multiple pheochromocytoma, extra-adrenal location, and previous head and neck paraganglioma. If we used the presence of any one predictor as indicative of proceeding with gene testing, then 342 (34.6%) patients would be excluded, and only 8 carriers (4.3%) would be missed. We were also able to statistically model the priority of genes to be tested given certain clinical features. E.g., for patients with prior head and neck paraganglioma, the priority would be SDHD>SDHB>RET>VHL. Using the clinical predictor algorithm to prioritize gene testing and order, a 44.7% cost reduction in diagnostic process can be achieved. Clinical parameters can predict for mutation carriers and help prioritize gene testing to reduce costs in nonsyndromic pheochromocytoma presentations.

Multiple Pheochromocytomas in a Patient With Blurred Vision

We report on a 19-year-old male diagnosed with multiple pheochromocytomas after an I-123 metaiodobenzylguanidine (MIBG) scan. Multiple imaging was obtained because of concern for von Hippel-Lindau disease (VHL) after bilateral retinal angiomas were discovered on ophthalmologic consultation as a follow-up from the Emergency Department. Computed tomography (CT) and magnetic resonance imaging (MRI) were able to localize the adrenal and extra-adrenal tumors; however, accurate differentiation between pheochromocytomas and other adrenal tumors was not possible. I-123 MIBG is the test of choice for evaluating functionality and location of pheochromocytomas because of its high sensitivity and specificity. I-123 MIBG was performed before surgery to confirm that the lesions were indeed pheochromocytomas and also to rule out metastatic disease. He was started on alpha- and beta-blocker medication for at least 3 weeks, followed by surgery. The postoperative period was uneventful. DNA testing was performed and revealed mutations in the VHL gene previously reported to be associated with von Hippel-Lindau syndrome type II and genetic counseling was recommended. He was presented in urology tumor board conference with recommendations for follow-up CT and laboratory tests after 3 months. Otherwise, the patient is doing well and asymptomatic at this time.

Early identification of patients with von Hippel-Lindau disease at risk for pheochromocytoma.

von Hippel-Lindau disease (VHL) is an autosomal dominant familial syndrome that predisposes to the formation of tumors in multiple organ systems, including adrenal and extra-adrenal pheochromocytomas. However, fewer than 30% of VHL families develop pheochromocytomas. In recent years, this clinical heterogeneity has been correlated with missense mutations. The VHL patient requires vigilant, lifelong biochemical and radiographic screening for pheochromocytoma. Half of VHL pheochromocytomas present bilaterally, and there is a high incidence of recurrence after surgery. Because of the morbidity of bilateral total adrenalectomy with subsequent steroid replacement therapy, the recent therapeutic trend has been toward observation and minimally invasive adrenal-sparing procedures.

LAPAROSCOPIC SURGERY FOR PHEOCHROMOCYTOMA: ADRENALECTOMY, PARTIAL RESECTION, EXCISION OF PARAGANGLIOMAS

Purpose Surgical treatment of pheochromocytoma includes adrenalectomy, adrenal sparing surgery and excision of extraadrenal paragangliomas. We report our experience using laparoscopy for these procedures. Materials and Methods Between June 1992 and November 1997, 19 patients underwent laparoscopic surgery for pheochromocytoma. Of the patients 14 had solitary tumors, and 4 presented with bilateral pheochromocytomas and 1 or 2 additional paragangliomas. In 1 patient a recurrent pheochromocytoma was found in the contralateral adrenal following previous right adrenalectomy. One patient each had myocardiopathy, amaurosis and stroke secondary to severe hypertension. Two patients were pregnant. Results All solitary tumors were treated with laparoscopic adrenalectomy. Laparoscopic adrenal sparing surgery (4 cases, 2 bilateral) and bilateral adrenalectomy (1) were performed for multiple familial pheochromocytoma, and all paragangliomas were excised simultaneously. The pregnant patients underwent surgery at 16 and 20 weeks of gestation, respectively. All procedures were completed as planned. The rate of minor intraoperative and postoperative complications was 11% and 16%, respectively, and there were no major complications. In all patients the catecholamine levels returned to normal and no residual tumors were found at followup. None of the patients undergoing partial resection required steroid replacement therapy. Conclusions In experienced hands, laparoscopic surgery for solitary and multiple pheochromocytoma and paraganglioma is feasible and safe, and does not increase the specific risks associated with pheochromocytoma surgery.

Familial pheochromocytomas with unusual associations

Pheochromocytoma occurs in a familial patterm in approximately 10% of patients. Although most familial pheochromocytomas are an expression of the genetic abnormality of neuroectodermal dysplasia or the genetic syndrome of multiple endocrine neoplasia, some familial pheochromocytomas occur without associated disease. Two patients with familial pheochromocytoma are described. One had an extraadrenal tumor, producing severe renal artery stenosis and in whose family pheochromocytomas were found in three successive generations. A second had multiple pheochromocytomas associated with von Hippel-Lindau disease and a family member with multiple endocrine neoplasia type 2. The combinations and permutations of these genetic entities form discrete syndromes, with other peculiar interrelationships, pathologically related to an aberration in the migration, growth, and differentiation of the neural crest cells, and emphasizing their common neuroectodermal origin. The unique features that characterize the familial pheochromocytomas and cause diagnostic and therapeutic challenges are reviewed.

FAMILIAL PHEOCHROMOCYTOMA IN VON HIPPEL-LINDAU DISEASE

Pheochromocytoma developed in two members (a brother and sister) of a family inheriting von Hipple-Lindau disease is reported. The brother had multiple pheochromocytoma associated with reversible renal artery stenosis. His sister had malignant non-functioning pheochromocytoma with tumor embolus of the portal vein. She died of bleeding from gastric varix.The significance of regular screening including ultrasonography and computed tomography of the abdomen must be emphasized for family members of von Hippel-Lindau disease, because early detection of tumor is indispensable to improve the curability of malignant pheochromocytoma. In this sister' case we should reflect for delayed diagnosis of pheochromocytoma because of lacking screening.

Extra-adrenal pheochromoctoma causingrenal artery stenosis and implications of magnetic resonance imaging as diagnostic tool

Extra-adrenal pheochromocytoma causing renal artery stenosis is very uncommon.We describe a patient who had hypertension from this entity. Surgical excision of the mass corrected the renal artery stenosis without the need for bypass grafting; and the patient has remained normotensive Magnetic resonance imaging (MRI) showed an extremely bright lesion on T 2 weighted image, which is virtually pathognomonic. MRI is the most sensitive modality for the detection of an extra-adrenal or unsuspected multiple pheochromocytoma. This should obviate the need for routine abdominal exploration in the evaluation and treatment of pheochromocytoma. Therefore we strongly recommend magnetic resonance imaging in the management of adrenal masses in general and pheochromocytomas in particular.

Multiple neuroectodermal abnormalities in pheochromocytoma patients

AbstractA series of 80 consecutive pheochromocytoma patients operated on from 1956 to 1985 were investigated for other neuroectodermal abnormalities. Such abnormalities were found in 23 (29%) patients. Medullary thyroid carcinoma was the most common associated neuroectodermal abnormality followed by von Recklinghausen's neurofibromatosis. Other abnormalities were intracranial tumors, midgut carcinoid, and parathyroid hyperplasia. All 6 patients with multiple pheochromocytomas had other neuroectodermal abnormalities. In the total series, the 14 patients with hereditary disease had multiple neuroectodermal abnormalities (MNA). Hypertension occurred significantly less often in MNA patients (p&lt;0.05). All the MNA patients had benign adrenal pheochromocytoma. In 7 of 9 normotensive patients, pheochromocytoma was suspected because of the presence of other neuroectodermal abnormalities. None of these 9 patients had any cardio‐ or cerebrovascular complications, but these occurred in 22% of the hypertensive patients. No patient in the series died from pheochromocytoma, but 4 of 5 deceased MNA patients died as a result of their associated neuroectodermal disease. During the last decade, 40% of the pheochromocytoma patients had MNA diagnosed compared to 20% during the previous period. An increased observation for other neuroectodermal abnormalities in pheochromocytoma patients and for pheochromocytoma in patients with neuroectodermal abnormalities should lead to earlier diagnosis and a better prognosis for the patients concerned.

Unilateral Versus Bilateral Adrenalectomy in Multiple Endocrine Neoplasia IIA

Factors influencing the result of various forms of surgical treatment for pheochromocytoma were studied in patients with multiple endocrine neoplasia IIA (MEN IIA) syndrome. The material consisted of 18 patients belonging to 4 non-related families operated on during 1966–1981 with a mean follow-up time of 7.4 years. Twenty-seven adrenals were removed at 22 operations. In all adrenals, multiple pheochromocytomas and/or medullary hyperplasia were present. In 13 patients the first operation was a unilateral adrenalectomy. Four of these had to be reoperated on because of recurring or persisting symptoms. Five patients were operated on bilaterally at the first instance. In 4 of these, the reason was bilateral macroscopic tumor involvement. Various pre- and intraoperative findings were evaluated with respect to the surgical result. The maximum diameter of the largest tumor was the only factor relating positively to surgical success with unilateral operation. Of 9 patients who remained asymptomatic following unilateral adrenalectomy, 8 had tumors less than 5 cm in diameter. The 4 patients who had to be reoperated on with a contralateral adrenalectomy all had a maximum tumor diameter exceeding 5 cm. A pragmatic approach to the problem of timing and extent of adrenal surgery in MEN IIA is advocated. Clinical, biochemical, histopathological, genetic, and social dimensions of the disease should be taken into consideration when choosing the surgical procedure.

Unilateral versus bilateral adrenalectomy in multiple endocrine neoplasia IIA.

AbstractFactors influencing the result of various forms of surgical treatment for pheochromocytoma were studied in patients with multiple endocrine neoplasia IIA (MEN IIA) syndrome. The material consisted of 18 patients belonging to 4 non‐related families operated on during 1966–1981 with a mean follow‐up time of 7.4 years. Twenty‐seven adrenals were removed at 22 operations. In all adrenals, multiple pheochromocytomas and/or medullary hyperplasia were present. In 13 patients the first operation was a unilateral adrenalectomy. Four of these had to be reoperated on because of recurring or persisting symptoms. Five patients were operated on bilaterally at the first instance. In 4 of these, the reason was bilateral macroscopic tumor involvement. Various pre‐ and intraoperative findings were evaluated with respect to the surgical result. The maximum diameter of the largest tumor was the only factor relating positively to surgical success with unilateral operation. Of 9 patients who remained asymptomatic following unilateral adrenalectomy, 8 had tumors less than 5 cm in diameter. The 4 patients who had to be reoperated on with a contralateral adrenalectomy all had a maximum tumor diameter exceeding 5 cm. A pragmatic approach to the problem of timing and extent of adrenal surgery in MEN IIA is advocated. Clinical, biochemical, histopathological, genetic, and social dimensions of the disease should be taken into consideration when choosing the surgical procedure.