0
We're unable to sign you in at this time. Please try again in a few minutes.
Retry
We were able to sign you in, but your subscription(s) could not be found. Please try again in a few minutes.
Retry
There may be a problem with your account. Please contact the AMA Service Center to resolve this issue.
Contact the AMA Service Center:
Telephone: 1 (800) 262-2350 or 1 (312) 670-7827  *   Email: subscriptions@jamanetwork.com
Error Message ......
Original Article |

Estimated Risk of Pheochromocytoma Recurrence After Adrenal-Sparing Surgery in Patients With Multiple Endocrine Neoplasia Type 2A FREE

Reza Asari, MD; Christian Scheuba, MD; Klaus Kaczirek, MD; Bruno Niederle, MD
[+] Author Affiliations

Author Affiliations: Division of General Surgery, Section of Endocrine Surgery (Drs Asari, Scheuba, and Kaczirek), and Department of Surgery (Dr Niederle), Medical University of Vienna, Vienna, Austria.


Arch Surg. 2006;141(12):1199-1205. doi:10.1001/archsurg.141.12.1199.
Text Size: A A A
Published online

Hypothesis  Adrenal-sparing adrenalectomy is considered the treatment of choice for hereditary bilateral pheochromocytoma in patients with multiple endocrine neoplasia type 2A (MEN 2A).

Design  Retrospective analysis of prospectively documented data with a mean ± SD follow-up of 81.5 ± 85.3 months. The PubMed database was searched for articles published between 1975 and 2004 to identify published series and/or case reports.

Setting  University hospital referral center.

Patients  In 17 (22%) of 77 patients with various mutations of the RET proto-oncogene, unilateral (n = 12) or bilateral (n = 5) pheochromocytomas were documented at the time of diagnosis or during the course of MEN 2A. Adrenal-sparing surgery was performed in 13 patients (group 1), synchronous bilateral total adrenalectomy in 4 patients (group 2A), and metachronous bilateral total adrenalectomy in 5 patients after adrenal-sparing adrenalectomy (group 2B).

Main Outcome Measures  Measurement of 24-hour urinary catecholamine levels (noradrenaline, adrenaline, and dopamine) and, in case of high catecholamine levels, imaging studies to localize the tumors in 1 or both adrenal glands to determine the size and exclude extra-adrenal tumors and distant metastasis.

Results  The mean±SD estimated 5- and 10-year cumulative risk of developing recurrence in both groups was 38.5% ± 15.7%. Five (38%) of 13 patients in group 1 developed recurrence in the contralateral gland. Two (22%) of 9 patients in groups 2A and 2B developed several episodes of an addisonian crisis, 1 of whom died.

Conclusions  Substantial morbidity and mortality are associated with addisonian crisis after bilateral adrenalectomy. Adrenal-sparing adrenalectomy and close monitoring of the remnant may be the treatment of choice for hereditary bilateral pheochromocytoma in MEN 2A, since overall recurrence is low.

Figures in this Article

Pheochromocytomas develop in 30% to 50% of patients with multiple endocrine neoplasia type 2 (MEN 2).1 On the cellular level, patients with MEN 2 are uniformly at risk for circumscribed bilateral tumors and/or have hyperplasia of the adrenal medulla even if this is not clinically or radiologically apparent at first presentation.2

The treatment of pheochromocytoma in patients with MEN 2A is controversial. Because both adrenal glands are affected, total bilateral adrenalectomy has been proposed by some authors as an appropriate therapy in patients with RET proto-oncogene mutations. This procedure may prevent the development of persistent or recurrent adrenal disease with the risk of hypertensive crisis after any kind of adrenal-sparing surgery.3 However, this approach necessitates long-term corticosteroid therapy with the social implications of complete dependence on lifelong substitution and the risk of osteoporosis with inadequately high substitution. A too low substitution is associated with the risk of life-threatening addisonian crisis. Therefore, other physicians have recommended a more selective approach of only resecting localized tumors with subsequent close monitoring of the remnants.4 This study aims to evaluate the risk of recurrence after adrenal-sparing surgery and the consequences of total bilateral adrenalectomy in patients with MEN 2A.

Seventy-seven patients (31 men and 46 women; mean ± SD age, 39.9 ± 20.3 years) with various mutations of the RET proto-oncogene were analyzed for the presence of pheochromocytoma. Molecular genetic analysis included exons 8, 10, 11, and 13 to 15 of the RET proto-oncogene by analysis of single-strand conformation polymorphisms and direct sequencing in all patients.5

Biochemical diagnosis of pheochromocytoma included measurement of 24-hour urinary catecholamine levels (noradrenaline, adrenaline, and dopamine), and in case of high catecholamine levels, imaging studies were performed to localize the tumors in 1 or both adrenal glands to determine the size and exclude extra-adrenal tumors and distant metastasis. These imaging studies included meta-iodobenzylguanidine scintigraphy, computed tomography, and/or magnetic resonance imaging.

If a catecholamine-producing tumor was diagnosed, patients were operated on either by adrenal-sparing surgery (subtotal adrenalectomy indicates unilateral adrenalectomy with or without contralateral subtotal resection) in circumscribed tumors or by synchronous or metachronous total bilateral adrenalectomy in large bilateral lesions. All patients were operated on by an experienced endocrine surgeon (B.N.). The surgical procedure was performed by a conventional open approach in 8 patients. An endoscopic transperitoneal access was favored and chosen in 9 patients. In 1 patient, a conversion from an endoscopic to an open procedure was necessary because of an injury of the tumor capsule during tumor mobilization. After surgery, all patients were observed by means of clinical examinations, including computed tomography and/or magnetic resonance imaging and measurement of 24-hour urinary catecholamine levels once a year.

Recurrence of pheochromocytoma was defined as the new development of elevated urinary catecholamine levels and the presence of a documented new intra-abdominal mass. Patients with recurrence were treated by endoscopic adrenalectomy of the adrenal remnant, thus resulting in metachronous total adrenalectomy in all patients.

Data analysis was performed using the statistical package SPSS version 11.5 for Windows (SPSS Inc, Chicago, Ill) to perform Kaplan-Meier estimations.

Because of the limited experience in treating patients with pheochromocytoma in MEN 2A in general and the recurrence and malignancy of these tumors, an analysis of the literature seemed necessary to find more patients with MEN 2A observed by other centers. An extensive search of the literature between January 1975 and December 2004 was conducted to identify published series and/or case reports. For this purpose, the PubMed database was consulted. The keywords adrenal-sparing surgery, subtotal/total adrenalectomy,MEN 2, and recurrence were used. The bibliographies of the retrieved articles were reviewed to find additional sources of data. All articles in English and German were initially considered. When articles that described the same patient(s) were reviewed, only those containing the most information on patient characteristics and outcomes were included. Thus, only references (case reports and articles) that provided sufficient data on diagnosis, surgical procedures, and outcome (recurrence and malignancy of tumor) were included in the analysis. References with insufficient data were excluded from further evaluations. Patients with MEN 2B were excluded from all analyses.

Seventeen (22%) of 77 RET proto-oncogene carriers had pheochromocytoma. Twelve patients (71%) had unilateral and 5 (29%) had bilateral tumors at the time of the diagnosis of catecholamine excess. The mean ± SD age at the first diagnosis was 47.7 ± 17.8 years (range, 23-75 years). There were 8 men (47%) and 9 women (53%). In 12 (71%) of 17 patients (15%), the catecholamine-producing tumor was the first manifestation of MEN 2A (Table 1).

Table Graphic Jump LocationTable 1. Demographics of the Study Population*

Two patients (12%) experienced additional extra-adrenal pheochromocytomas during the initial operation. In 1 of them, the extra-adrenal pheochromocytoma was localized above the renal vein on the left side and the other behind the inferior caval vein. In none of the patients was malignancy documented at the time of surgery or during follow-up.

Seven patients (41%) had a mutation at codon 634, 5 (29%) at codon 611, 3 (18%) at codon 620, 1 (6%) at codon 791, and 1 (6%) at codon 891 (Table 2). All patients except 1 (patient 8) had medullary thyroid cancer, and 3 patients (patients 4, 15, and 16) had primary hyperparathyroidism (Table 3).

Table Graphic Jump LocationTable 2. Results of Genetic Testing in Patients With Multiple Endocrine Neoplasia Type 2A and Pheochromocytoma
Table Graphic Jump LocationTable 3. Effect of Adrenal Tumor on Thyroid and Parathyroid Glands
GROUP 1

Four (31%) of 13 patients had a mutation at codon 634, 4 patients (31%) had a mutation at codon 611, 3 patients (23%) had a mutation at codon 620, and 2 patients (15%) had mutations at codon 791 and 891. Twelve of 13 patients underwent primary unilateral adrenalectomy on the affected side without involvement of the contralateral adrenal gland. One patient who had bilateral pheochromocytomas at the time of diagnosis underwent subtotal adrenal resection with the remnant on the right side after total removal of the left tumor-bearing adrenal gland. After surgery, all patients had sufficient adrenal function without hormone therapy.

Within the observation period of 81.5 months, 5 (38%) of 13 patients with unilateral adrenalectomy developed recurrence (mean ± SD disease-free survival, 79.9 ± 95.7 months). Three of them had a mutation at codon 634, and 2 had a mutation at codon 611. In further descriptions and analysis, these patients are included in group 2B. Further follow-up analysis continued with the subsequent operation. None of the patients with mutations at codon 620, 891, or 791 developed a recurrence during the observation period. No operative or perioperative mortality or morbidity occurred.

GROUP 2A

Four patients who had tumors in both adrenal glands that measured 10 to 60 mm underwent primary synchronous bilateral adrenalectomy. Three patients had a mutation at codon 634 and 1 of codon 611. No operative or perioperative mortality or morbidity occurred in this group. During the observation period (mean ± SD, 79.0 ± 68.8 months), no recurrence of disease was seen (mean ± SD disease-free survival, 78.9 ± 68.7 months). All patients needed postoperative hormone therapy. Two of them developed an addisonian crisis, 1 of whom died during it.

GROUP 2B

Five patients developed recurrence after unilateral adrenalectomy (mean ± SD disease-free survival, 99.7 ± 141.7 months). In these patients contralateral adrenalectomy was performed, resulting in metachronous total adrenalectomy. Because of the size of the pheochromocytoma that involved the whole gland, no organ-sparing adrenal resection was possible. All patients except for 1 were cured of the catecholamine excess. This patient, with a mutation at codon 634, developed an extra-adrenal pheochromocytoma on the left side of the aorta 13 years after metachronous total adrenalectomy.

ESTIMATED CUMULATIVE RISK OF RECURRENCE

The mean ± SD estimated 5- and 10-year cumulative risk of developing recurrence was 38.5% ± 15.7% (3 patients at risk), analyzing all patients (Figure 1). The mean ± SD estimated 5- and 10-year cumulative risk for patients in group 1 was 51.8% ± 18.7% (2 patients at risk; Figure 2); the mean ± SD estimated 15-year cumulative risk for group 2 (A and B) was 34% ± 27.2% (1 patient at risk; Figure 3).

Place holder to copy figure label and caption
Figure 1.

Estimated cumulative recurrence-free survival (Kaplan-Meier curve) of all patients independent of the surgical strategy at 5 years (38.5% ± 15.7%; 5 patients at risk) and 10 years (38.5% ± 15.7%; 3 patients at risk).

Graphic Jump Location
Place holder to copy figure label and caption
Figure 2.

Estimated cumulative recurrence-free survival (Kaplan-Meier curve) of group 1 (adrenal-sparing adrenalectomy) at 5 years (51.8% ± 18.7%; 3 patients at risk) and 10 years (51.8% ± 18.7%; 2 patients at risk).

Graphic Jump Location
Place holder to copy figure label and caption
Figure 3.

Estimated cumulative recurrence-free survival (Kaplan-Meier curve) of groups 2A and 2B (metachronous total adrenalectomy) at 15 years (34% ± 27.2%; 1 patient at risk).

Graphic Jump Location
REVIEW OF LITERATURE

By definition, 21 publications were found to describe patients with MEN 2A (Table 4A and 4B). Four studies6,8,10,15 had no data concerning recurrent pheochromocytoma or surgical procedure, and 1 publication described a case report.19 Altogether, these 118 patients were excluded from further analysis. Including this series, 348 patients were suitable for evaluating surgical strategy in case of recurrence, malignancy, or addisonian crisis. The mean follow-up of these patients was 89 months (range, 1-375 months).

Table Graphic Jump LocationTable 4. Results of Adrenalectomy in Patients With Multiple Endocrine Neoplasia Type 2A (Literature Review, 1975-2004)

Data on recurrent pheochromocytoma after adrenal-sparing adrenalectomy were given in 15 studies.3,7,918,20,22,23 Fifty-eight (31%) of 187 patients developed a recurrent pheochromocytoma in either the ipsilateral or contralateral adrenal remnant. The interval to developing recurrent disease was a median of 83.5 months (range, 1-375 months). Surgical procedures for the recurrent pheochromocytoma included a total adrenalectomy of the affected adrenal gland in 57 of 58 patients. One patient described by Walz et al21 was treated by an adrenal-sparing procedure of the affected gland during a subsequent operation (Table 4).

A total of 161 patients underwent total bilateral adrenalectomy for the initial procedure. Five (3%) of these patients developed a recurrent pheochromocytoma after a median interval of 234 months (range, 23-375 months) (Table 4).

Fourteen patients with a malignant pheochromocytoma due to MEN 2A were described in the literature. Six of these patients underwent adrenal-sparing surgery8,10; unfortunately, no data were available on their follow-up. Eight patients with a malignant pheochromocytoma were treated by a synchronous total bilateral adrenalectomy6,10,11,13,17; 2 of them had a mean follow-up of 84 and 59 months, and none of them developed recurrence.13,17 No data were available on follow-up in the other 6 patients.6,10,11

Approximately 50% of MEN 2A gene carriers develop pheochromocytomas.1 Seventeen (22%) of 77 patients with various types of RET mutations had unilateral or bilateral pheochromocytomas at the time of diagnosis or during follow-up. Because the MEN 2A syndrome is rare, no single center has sufficient experience with the best treatment of this disease. Therefore, we analyzed our patients in connection with data published in the literature to estimate the risk of recurrence after various types of adrenal surgery, to analyze the risk of malignancy, and to evaluate the consequences of total bilateral adrenalectomy.

Early diagnosis and treatment of catecholamine excess are mandatory to avoid life-threatening complications. Thus, in genetically determined hereditary medullary thyroid cancer, an extended search for pheochromocytoma is the rule before treating the disease and during follow-up, if the initial test results are negative. Catecholamine-producing tumors may develop synchronously or metachronously.

Different codon mutations in the RET proto-oncogene have been associated with a higher frequency of pheochromocytoma. Eng et al25 described a strongly associated presence of pheochromocytoma in any mutation in codon 634. They also found pheochromocytomas in patients with mutations of codons 611, 618, and 620. Other mutations in RET codons 609, 790, 791, 804, and 891 have also been associated with pheochromocytoma in patients with MEN 2A.2529 The development of pheochromocytoma seems to be associated with specific codon mutations. In 15 (88%) of 17 patients, pheochromocytomas were documented in connection with a mutation in the cysteine-rich extracellular domain of the RET proto-oncogene and only in 2 patients with a mutation in the intracellular domain. Up to now (contralateral) recurrence was observed only in patients with mutations of codons 634 and 611.

On the basis of its pathophysiologic features, all adrenal and extra-adrenal medullary tissue is affected by the molecular defect and incorporates the risk of developing catecholamine excess; thus, the theory that a surgical strategy (radical, bilateral, or subtotal) is best for each patient is still under discussion. The mean ± SD cumulative estimated risk of developing recurrent pheochromocytoma in 5 or 10 years was 38.5% ± 15.7%, analyzing all patients. The cumulative estimated risk of developing recurrent contralateral pheochromocytoma in patients who underwent unilateral adrenalectomy with or without contralateral subtotal resection was 51.8% ± 18.7%. Even in patients with a primary bilateral total adrenalectomy, 1 patient developed an extra-adrenal pheochromocytoma 13 years after total adrenalectomy. When a recurrence in the remnant gland developed, an additional subtotal adrenalectomy could be performed without perioperative morbidity to avoid permanent adrenocortical hormone therapy.30 A subsequent operation can be performed endoscopically with success.21

To minimize the risk of recurrence in the contralateral adrenal gland or the remnant left in situ, some authors advocate bilateral total adrenalectomy in all patients.3 The price for this kind of radical surgical treatment is the necessity of adrenocortical hormone substitution with the risk of osteoporosis, the social implications of complete dependence on lifelong substitution, and potential development of an addisonian crisis. Addisonian crisis after bilateral adrenalectomy is described in up to 35% of patients, with a 3% mortality rate reported in the literature.3,12,31 In the literature review (Table 4), 25 (15%) of 164 patients who underwent a total bilateral adrenalectomy procedure developed an addisonian crisis during their postoperative follow-up. Although every patient undergoing an adrenal surgical procedure is informed of the potential medical hazards and necessity of treatment for different stress situations, 2 (22%) of 9 patients in our series who underwent a total bilateral adrenalectomy developed an addisonian crisis, with frequent hospital admissions for adjustment of corticosteroid therapy. One female patient (11%) died during an addisonian crisis followed by a gastrointestinal infection.

In a study that evaluated quality of life after bilateral total adrenalectomy in 27 patients with MEN 2,32 fatigue, worry, and noncompliance were encountered in 40% of the patients. One third of these patients needed more hospital admissions than usual and described, besides chronic fatigue, constant psychological pressure and difficulties in taking medicine as prescribed.

Malignant pheochromocytomas are rare in MEN 2A.23 Only 6 (2%) of 348 patients with MEN 2A had a malignant histopathologic tumor.6,8,10,11,13 In our series, we could not find any patient with a malignant pheochromocytoma. In case of malignant recurrence, morbidity and mortality can be minimized by close monitoring and early therapy.

The risk of slowly growing, benign, recurrent pheochromocytoma seems low and must be weighed against the morbidity and mortality associated with addisonian crisis after bilateral adrenalectomy. Therefore, we recommend adrenal-sparing adrenalectomy (unilateral adrenalectomy in unilateral tumors and unilateral adrenalectomy with subtotal contralateral adrenalectomy in small bilateral tumors) and close monitoring of the remnant as the treatment of choice for hereditary bilateral pheochromocytomas.

Correspondence: Reza Asari, MD, Section of Endocrine Surgery, Division of General Surgery, Department of Surgery, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria (reza.asari@meduniwien.ac.at).

Accepted for Publication: October 14, 2006.

Author Contributions:Study concept and design: Niederle. Acquisition of data: Asari, Scheuba, and Kaczirek. Analysis and interpretation of data: Asari. Drafting of the manuscript: Asari. Critical revision of the manuscript for important intellectual content: Scheuba, Kaczirek, and Niederle. Statistical analysis: Asari. Obtained funding: Asari, Scheuba, and Kaczirek. Administrative, technical, and material support: Asari. Study supervision: Niederle.

Financial Disclosure: None reported.

Evans  DBLee  JEMerrell  RCHickey  RC Adrenal medullary disease in multiple endocrine neoplasia type 2: appropriate management. Endocrinol Metab Clin North Am 1994;23167- 176
PubMed
Lips  KJVan der Sluys Veer  JStruyvenberg  A  et al.  Bilateral occurrence of pheochromocytoma in patients with the multiple endocrine neoplasia syndrome type 2A (Sipple's syndrome). Am J Med 1981;701051- 1060
PubMed Link to Article
van Heerden  JASizemore  GWCarney  JA  et al.  Surgical management of the adrenal glands in the multiple endocrine neoplasia type II syndrome. World J Surg 1984;8612- 621
PubMed Link to Article
Neumann  HPReincke  MBender  BUElsner  RJanetschek  G Preserved adrenocortical function after laparoscopic bilateral adrenal sparing surgery for hereditary pheochromocytoma. J Clin Endocrinol Metab 1999;842608- 2610
PubMed
Fink  MWeinhusel  ANiederle  BHaas  OA Distinction between sporadic and hereditary medullary thyroid carcinoma (MTC) by mutation analysis of the RET proto-oncogene. Study Group Multiple Endocrine Neoplasia Austria (SMENA). Int J Cancer 1996;69312- 316
PubMed Link to Article
Wilson  RAIbanez  ML A comparative study of 14 cases of familial and nonfamilial pheochromocytomas. Hum Pathol 1978;9181- 188
PubMed Link to Article
Tibblin  SDymling  JFIngemansson  STelenius-Berg  M Unilateral versus bilateral adrenalectomy in multiple endocrine neoplasia IIA. World J Surg 1983;7201- 208
PubMed Link to Article
Shapiro  BCopp  JESisson  JC  et al.  Iodine-131 metaiodobenzylguanidine for the locating of suspected pheochromocytoma: experience in 400 cases. J Nucl Med 1985;26576- 585
PubMed
Jansson  STisell  LEFjalling  M  et al.  Early diagnosis of and surgical strategy for adrenal medullary disease in MEN II gene carriers. Surgery 1988;10311- 18
PubMed
Oishi  SSasaki  MYamauchi  JUmeda  TSato  T Analysis of eight Sipple's syndrome patients and review of eighty-two cases from the Japanese literature. Jpn J Clin Oncol 1990;20392- 406
PubMed
Casanova  SRosenberg-Bourgin  MFarkas  D  et al.  Phaeochromocytoma in multiple endocrine neoplasia type 2 A: survey of 100 cases. Clin Endocrinol (Oxf) 1993;38531- 537
PubMed Link to Article
Lairmore  TCBall  DWBaylin  SBWells  SA  Jr Management of pheochromocytomas in patients with multiple endocrine neoplasia type 2 syndromes. Ann Surg 1993;217595- 603
PubMed Link to Article
Goretzki  PESDotzenrath  DRöher  C Surgery for pheochromocytoma in MEN II patients: a radical versus a limited approach. Acta Chir Aust 1996;28296- 301
Link to Article
Edstrom  EGrondal  SNorstrom  F  et al.  Long term experience after subtotal adrenalectomy for multiple endocrine neoplasia type IIa. Eur J Surg 1999;165431- 435
PubMed Link to Article
Neumann  HPBender  BUReincke  M  et al.  Adrenal-sparing surgery for phaeochromocytoma. Br J Surg 1999;8694- 97
PubMed Link to Article
de Graaf  JSDZwierstra  RPF Complications after bilateral adrenalectomy for phaeochromocytoma in multiple endocrine neoplasia type 2: a plea to conserve adrenal function. Eur J Surg 1999;165843- 846
PubMed Link to Article
Inabnet  WBCaragliano  PPertsemlidis  D Pheochromocytoma: inherited associations, bilaterality, and cortex preservation. Surgery 2000;1281007- 1011
PubMed Link to Article
Nguyen  LNiccoli-Sire  PCaron  P  et al.  Pheochromocytoma in multiple endocrine neoplasia type 2: a prospective study. Eur J Endocrinol 2001;14437- 44
PubMed Link to Article
Takami  HIkeda  YTakayama  J  et al.  Adrenal-sparing adrenalectomy in hereditary bilateral phaeochromocytoma. ANZ J Surg 2001;71623- 624
PubMed Link to Article
Brunt  LMLairmore  TCDoherty  GM  et al.  Adrenalectomy for familial pheochromocytoma in the laparoscopic era. Ann Surg 2002;235713- 721
PubMed Link to Article
Walz  MKPeitgen  KNeumann  HP  et al.  Endoscopic treatment of solitary, bilateral, multiple, and recurrent pheochromocytomas and paragangliomas. World J Surg 2002;261005- 1012
PubMed Link to Article
Brauckhoff  MNguyen Thanh  PBar  ADralle  H Subtotal bilateral adrenalectomy preserving adrenocortical function [in German]. Chirurg 2003;74646- 651
PubMed Link to Article
Yip  LLee  JEShapiro  SE  et al.  Surgical management of hereditary pheochromocytoma. J Am Coll Surg 2004;198525- 535
PubMed Link to Article
Goldstein  REO’Neill  JA  JrHolcomb  GW  et al.  Clinical experience over 48 years with pheochromocytoma. Ann Surg 1999;229755- 764
PubMed Link to Article
Eng  CClayton  DSchuffenecker  I  et al.  The relationship between specific RET proto-oncogene mutations and disease phenotype in multiple endocrine neoplasia type 2: international RET mutation consortium analysis. JAMA 1996;2761575- 1579
PubMed Link to Article
Machens  ABrauckhoff  MHolzhausen  HJThanh  PNLehnert  HDralle  H Codon-specific development of pheochromocytoma in multiple endocrine neoplasia type 2. J Clin Endocrinol Metab 2005;903999- 4003
PubMed Link to Article
Brandi  MLGagel  RFAngeli  A  et al.  Guidelines for diagnosis and therapy of MEN type 1 and type 2. J Clin Endocrinol Metab 2001;865658- 5671
PubMed Link to Article
Igaz  PPatocs  ARacz  K  et al.  Occurrence of pheochromocytoma in a MEN2A family with codon 609 mutation of the RET proto-oncogene. J Clin Endocrinol Metab 2002;872994
PubMed Link to Article
Jimenez  CHabra  MAHuang  SC  et al.  Pheochromocytoma and medullary thyroid carcinoma: a new genotype-phenotype correlation of the RET protooncogene 891 germline mutation. J Clin Endocrinol Metab 2004;894142- 4145
PubMed Link to Article
Brauckhoff  MGimm  OBrauckhoff  KDralle  H Repeat adrenocortical-sparing adrenalectomy for recurrent hereditary pheochromocytoma. Surg Today 2004;34251- 255
PubMed Link to Article
de Graaf  JSLips  CJRutter  JEvan Vroonhoven  TJ Subtotal adrenalectomy for phaeochromocytoma in multiple endocrine neoplasia type 2A. Eur J Surg 1999;165535- 538
PubMed Link to Article
Telenius-Berg  MPonder  MABerg  BPonder  BAWerner  S Quality of life after bilateral adrenalectomy in MEN 2. Henry Ford Hosp Med J 1989;37160- 163
PubMed

Figures

Place holder to copy figure label and caption
Figure 1.

Estimated cumulative recurrence-free survival (Kaplan-Meier curve) of all patients independent of the surgical strategy at 5 years (38.5% ± 15.7%; 5 patients at risk) and 10 years (38.5% ± 15.7%; 3 patients at risk).

Graphic Jump Location
Place holder to copy figure label and caption
Figure 2.

Estimated cumulative recurrence-free survival (Kaplan-Meier curve) of group 1 (adrenal-sparing adrenalectomy) at 5 years (51.8% ± 18.7%; 3 patients at risk) and 10 years (51.8% ± 18.7%; 2 patients at risk).

Graphic Jump Location
Place holder to copy figure label and caption
Figure 3.

Estimated cumulative recurrence-free survival (Kaplan-Meier curve) of groups 2A and 2B (metachronous total adrenalectomy) at 15 years (34% ± 27.2%; 1 patient at risk).

Graphic Jump Location

Tables

Table Graphic Jump LocationTable 1. Demographics of the Study Population*
Table Graphic Jump LocationTable 2. Results of Genetic Testing in Patients With Multiple Endocrine Neoplasia Type 2A and Pheochromocytoma
Table Graphic Jump LocationTable 3. Effect of Adrenal Tumor on Thyroid and Parathyroid Glands
Table Graphic Jump LocationTable 4. Results of Adrenalectomy in Patients With Multiple Endocrine Neoplasia Type 2A (Literature Review, 1975-2004)

References

Evans  DBLee  JEMerrell  RCHickey  RC Adrenal medullary disease in multiple endocrine neoplasia type 2: appropriate management. Endocrinol Metab Clin North Am 1994;23167- 176
PubMed
Lips  KJVan der Sluys Veer  JStruyvenberg  A  et al.  Bilateral occurrence of pheochromocytoma in patients with the multiple endocrine neoplasia syndrome type 2A (Sipple's syndrome). Am J Med 1981;701051- 1060
PubMed Link to Article
van Heerden  JASizemore  GWCarney  JA  et al.  Surgical management of the adrenal glands in the multiple endocrine neoplasia type II syndrome. World J Surg 1984;8612- 621
PubMed Link to Article
Neumann  HPReincke  MBender  BUElsner  RJanetschek  G Preserved adrenocortical function after laparoscopic bilateral adrenal sparing surgery for hereditary pheochromocytoma. J Clin Endocrinol Metab 1999;842608- 2610
PubMed
Fink  MWeinhusel  ANiederle  BHaas  OA Distinction between sporadic and hereditary medullary thyroid carcinoma (MTC) by mutation analysis of the RET proto-oncogene. Study Group Multiple Endocrine Neoplasia Austria (SMENA). Int J Cancer 1996;69312- 316
PubMed Link to Article
Wilson  RAIbanez  ML A comparative study of 14 cases of familial and nonfamilial pheochromocytomas. Hum Pathol 1978;9181- 188
PubMed Link to Article
Tibblin  SDymling  JFIngemansson  STelenius-Berg  M Unilateral versus bilateral adrenalectomy in multiple endocrine neoplasia IIA. World J Surg 1983;7201- 208
PubMed Link to Article
Shapiro  BCopp  JESisson  JC  et al.  Iodine-131 metaiodobenzylguanidine for the locating of suspected pheochromocytoma: experience in 400 cases. J Nucl Med 1985;26576- 585
PubMed
Jansson  STisell  LEFjalling  M  et al.  Early diagnosis of and surgical strategy for adrenal medullary disease in MEN II gene carriers. Surgery 1988;10311- 18
PubMed
Oishi  SSasaki  MYamauchi  JUmeda  TSato  T Analysis of eight Sipple's syndrome patients and review of eighty-two cases from the Japanese literature. Jpn J Clin Oncol 1990;20392- 406
PubMed
Casanova  SRosenberg-Bourgin  MFarkas  D  et al.  Phaeochromocytoma in multiple endocrine neoplasia type 2 A: survey of 100 cases. Clin Endocrinol (Oxf) 1993;38531- 537
PubMed Link to Article
Lairmore  TCBall  DWBaylin  SBWells  SA  Jr Management of pheochromocytomas in patients with multiple endocrine neoplasia type 2 syndromes. Ann Surg 1993;217595- 603
PubMed Link to Article
Goretzki  PESDotzenrath  DRöher  C Surgery for pheochromocytoma in MEN II patients: a radical versus a limited approach. Acta Chir Aust 1996;28296- 301
Link to Article
Edstrom  EGrondal  SNorstrom  F  et al.  Long term experience after subtotal adrenalectomy for multiple endocrine neoplasia type IIa. Eur J Surg 1999;165431- 435
PubMed Link to Article
Neumann  HPBender  BUReincke  M  et al.  Adrenal-sparing surgery for phaeochromocytoma. Br J Surg 1999;8694- 97
PubMed Link to Article
de Graaf  JSDZwierstra  RPF Complications after bilateral adrenalectomy for phaeochromocytoma in multiple endocrine neoplasia type 2: a plea to conserve adrenal function. Eur J Surg 1999;165843- 846
PubMed Link to Article
Inabnet  WBCaragliano  PPertsemlidis  D Pheochromocytoma: inherited associations, bilaterality, and cortex preservation. Surgery 2000;1281007- 1011
PubMed Link to Article
Nguyen  LNiccoli-Sire  PCaron  P  et al.  Pheochromocytoma in multiple endocrine neoplasia type 2: a prospective study. Eur J Endocrinol 2001;14437- 44
PubMed Link to Article
Takami  HIkeda  YTakayama  J  et al.  Adrenal-sparing adrenalectomy in hereditary bilateral phaeochromocytoma. ANZ J Surg 2001;71623- 624
PubMed Link to Article
Brunt  LMLairmore  TCDoherty  GM  et al.  Adrenalectomy for familial pheochromocytoma in the laparoscopic era. Ann Surg 2002;235713- 721
PubMed Link to Article
Walz  MKPeitgen  KNeumann  HP  et al.  Endoscopic treatment of solitary, bilateral, multiple, and recurrent pheochromocytomas and paragangliomas. World J Surg 2002;261005- 1012
PubMed Link to Article
Brauckhoff  MNguyen Thanh  PBar  ADralle  H Subtotal bilateral adrenalectomy preserving adrenocortical function [in German]. Chirurg 2003;74646- 651
PubMed Link to Article
Yip  LLee  JEShapiro  SE  et al.  Surgical management of hereditary pheochromocytoma. J Am Coll Surg 2004;198525- 535
PubMed Link to Article
Goldstein  REO’Neill  JA  JrHolcomb  GW  et al.  Clinical experience over 48 years with pheochromocytoma. Ann Surg 1999;229755- 764
PubMed Link to Article
Eng  CClayton  DSchuffenecker  I  et al.  The relationship between specific RET proto-oncogene mutations and disease phenotype in multiple endocrine neoplasia type 2: international RET mutation consortium analysis. JAMA 1996;2761575- 1579
PubMed Link to Article
Machens  ABrauckhoff  MHolzhausen  HJThanh  PNLehnert  HDralle  H Codon-specific development of pheochromocytoma in multiple endocrine neoplasia type 2. J Clin Endocrinol Metab 2005;903999- 4003
PubMed Link to Article
Brandi  MLGagel  RFAngeli  A  et al.  Guidelines for diagnosis and therapy of MEN type 1 and type 2. J Clin Endocrinol Metab 2001;865658- 5671
PubMed Link to Article
Igaz  PPatocs  ARacz  K  et al.  Occurrence of pheochromocytoma in a MEN2A family with codon 609 mutation of the RET proto-oncogene. J Clin Endocrinol Metab 2002;872994
PubMed Link to Article
Jimenez  CHabra  MAHuang  SC  et al.  Pheochromocytoma and medullary thyroid carcinoma: a new genotype-phenotype correlation of the RET protooncogene 891 germline mutation. J Clin Endocrinol Metab 2004;894142- 4145
PubMed Link to Article
Brauckhoff  MGimm  OBrauckhoff  KDralle  H Repeat adrenocortical-sparing adrenalectomy for recurrent hereditary pheochromocytoma. Surg Today 2004;34251- 255
PubMed Link to Article
de Graaf  JSLips  CJRutter  JEvan Vroonhoven  TJ Subtotal adrenalectomy for phaeochromocytoma in multiple endocrine neoplasia type 2A. Eur J Surg 1999;165535- 538
PubMed Link to Article
Telenius-Berg  MPonder  MABerg  BPonder  BAWerner  S Quality of life after bilateral adrenalectomy in MEN 2. Henry Ford Hosp Med J 1989;37160- 163
PubMed

Correspondence

CME
Also Meets CME requirements for:
Browse CME for all U.S. States
Accreditation Information
The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
Note: You must get at least of the answers correct to pass this quiz.
Please click the checkbox indicating that you have read the full article in order to submit your answers.
Your answers have been saved for later.
You have not filled in all the answers to complete this quiz
The following questions were not answered:
Sorry, you have unsuccessfully completed this CME quiz with a score of
The following questions were not answered correctly:
Commitment to Change (optional):
Indicate what change(s) you will implement in your practice, if any, based on this CME course.
Your quiz results:
The filled radio buttons indicate your responses. The preferred responses are highlighted
For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.
Submit a Comment

Multimedia

Some tools below are only available to our subscribers or users with an online account.

Web of Science® Times Cited: 36

Related Content

Customize your page view by dragging & repositioning the boxes below.

Articles Related By Topic
Related Collections
PubMed Articles