Pheochromocytoma in multiple endocrine neoplasia type II: an example of the two-hit theory of neoplasia

Six kindreds in which pheochromocytomas were present as manifestations of the autosomal dominantly inherited multiple endocrine neoplasia (MEN) type II were studied. The patients underwent bilateral total adrenalectomy with the finding that the pheochromocytomas were bilateral, multifocal, and associated with distinct medullary hyperplasia and reduction in the normal corticomedullary ratio-- features not usually seen in patients with sporadic pheochromocytoma. These findings were exemplified in recent cases of a 34-year-old woman and a 40-year-old man who both had undergone total thyroidectomy for medullary carcinoma of the thyroid. Diagnoses of pheochromocytoma were made by catecholamine studies, computerized tomography, and 131I meta-iodobenzylguanidine (MIBG) scan. Bilateral adrenalectomy was performed with the finding of multiple bilateral pheochromocytomas and adrenal medullary hyperplasia. As in hereditary medullary carcinoma of the thyroid, the histologic findings in pheochromocytomas of the MEN II syndrome are consistent with Knudson's two-mutational-event theory for the initiation of neoplasia, with adrenal medullary hyperplasia representing the manifestation of the first or genetic mutational event and being present invariably in the hereditary cases.     

Management of pheochromocytomas in patients with multiple endocrine neoplasia type 2 syndromes.

OBJECTIVE: The authors sought to determine the optimal surgical management of pheochromocytomas that develop in patients with multiple endocrine neoplasia (MEN) type 2 syndromes. SUMMARY BACKGROUND DATA: The performance of empirical bilateral adrenalectomy in patients with MEN 2A or MEN 2B, whether or not they have bilateral pheochromocytomas, is controversial. METHODS: The results of unilateral or bilateral adrenalectomy were studied in 58 patients (49 with MEN 2A and 9 with MEN 2B). Recurrence of disease was evaluated by measuring 24-hour urinary excretion rates of catecholamines and metabolites and by computed tomography (CT) scanning. RESULTS: The mean postoperative follow-up was 9.40 years. There was no operative mortality and malignant or extra-adrenal pheochromocytomas were not present. Twenty-three patients with a unilateral pheochromocytoma and a macroscopically normal contralateral gland underwent unilateral adrenalectomy. A pheochromocytoma developed in the remaining gland a mean of 11.87 years after the primary adrenalectomy in 12 (52%) patients. Conversely, 11 (48%) patients did not develop pheochromocytoma during a mean interval of 5.18 years. In the interval after unilateral adrenalectomy, no patient experienced hypertensive crises or other complications related to an undiagnosed pheochromocytoma. Ten (23%) of 43 patients having both adrenal glands removed (either at a single operation or sequentially) experienced at least one episode of acute adrenal insufficiency or Addisonian crisis, including one patient who died during a bout of influenza. CONCLUSIONS: Based on these data, the treatment of choice for patients with MEN 2A or MEN 2B and a unilateral pheochromocytoma is resection of only the involved gland. Substantial morbidity and significant mortality are associated with the Addisonian state after bilateral adrenalectomy.     

Bilateral pheochromocytomas with von Hippel-Lindau disease: a case report

A case of bilateral pheochromocytomas with von Hippel Lindau disease (VHL) is reported. A 32-year-old man visited Kumamoto Red Cross Hospital for further examination of hypertension. Computed tomography revealed bilateral adrenal tumors and noradrenalin levels in serum and urine were elevated. Suspecting bilateral pheochromocytoma, he was reffered to our hospital for further examination and treatment. 131I-MIBG scintigraphy showed accumulation in bilateral adrenal glands. Moreover, he had cerebellar and spinal hemangioblastomas. Bilateral adrenalectomies and left nephrectomy were performed because tumor thrombus extended into the left renal vein, and pathological diagnosis was pheochromocytoma. His sister had been diagnosed as VHL disease. We diagnosed the patient as VHL disease because of the existence of cerebellar and spinal hemangioblastomas, bilateral pheochromocytomas, missense mutation and his family history. This is the eleventh case of bilateral pheochromocytomas with VHL disease reported in Japanese literatures.     

Bilateral subtotal adrenal resection for bilateral pheochromocytomas in multiple endocrine neoplasia, type IIa: a case report

Our treatment philosophy for the management of the adrenal glands in patients with multiple endocrine neoplasia, type IIa has been bilateral total adrenalectomy. In the patient described, exceptional and pressing reasons necessitated preservation of adrenocortical function. Bilateral pheochromocytomas were resected with preservation of the adrenal cortices. Adrenocortical function was normal 36 months after resection. Although the patient remained symptom free, elevated basal immunoreactive plasma calcitonin levels suggested the presence of residual or metastatic medullary thyroid carcinoma. There was no evidence of recurrent pheochromocytoma.     

A case of Sipple syndrome whose bilateral pheochromocytomas were resected separately after a 3-year interval

A 23-year-old woman who had undergone total thyroidectomy and parabronchial lymphadenectomy at the Department of Otolaryngology in our hospital was suspected to have a thyroid carcinoma. Histological examination revealed a medullary carcinoma of the thyroid and normal parathyroid glands. Because a computed tomographic scan after surgery revealed a tumor of the left adrenal gland, the patient was examined at our department two months after the thyroidectomy, 1994. Endocrinic examinations and 123I-MIBG scintigraphy revealed a left adrenal pheochromocytoma of Sipple syndrome. She then underwent left adrenalectomy. Histological diagnosis was pheochromocytoma of the left adrenal gland. Three years after the surgery, a right adrenal tumor was detected by computed tomography. Although results of endocrine examinations were normal, 131I-MIBG scintigraphy showed a hot spot in the right adrenal gland. Right adrenal pheochromocytoma was diagnosed 3 years after surgery for a contralateral adrenal pheochromocytoma. Although surgery was recommended, the patient consented to right adrenalectomy, 1 year later after marriage and before becoming pregnant. Histological examination of the resected specimen revealed pheochromocytoma of the right adrenal gland.     

Limitations of 131I-MIBG scintigraphy in locating pheochromocytomas

131I-metaiodobenzylguanidine (131I-MIBG) scintigraphy for the location of pheochromocytomas has proved to be a major advance in patient management. In combination with computerized tomographic scanning, nearly all pheochromocytomas can be located before surgery and invasive investigations are now indicated only in exceptional cases. However, there are still lessons to be learned concerning the optimal administration and interpretation of 131I-MIBG scintigraphy. With careful attention to detail and an awareness of isotope distribution, false positive studies should be extremely rare. While the incidence of false negative studies is uncommon, these certainly occur. A patient with sporadic bilateral adrenal medullary hyperplasia, bilateral pheochromocytomas, and additional benign pheochromocytomas arising in paraganglia tissue anterior to the abdominal aorta is presented. The right adrenal pheochromocytoma was not identified on 131I-MIBG imaging. We conclude that even with current locating techniques, the traditional surgical approach to pheochromocytoma should not be abandoned. This involves transabdominal exploration of both adrenal glands and careful examination of all possible sites of extra-adrenal pheochromocytomas.     

Intraoperative radionuclear 125I-labeled metaiodobenzylguanidine scanning of pheochromocytomas and metastases.

We developed a technique to assess the feasibility of intraoperative radionuclear detection of pheochromocytomas and their metastases. Thirteen patients were entered into the study: five control subjects with nonchromaffin adrenal tumors, eight with pheochromocytomas, and one of these patients showing bone metastasis. Each subject received thyroid blockade and an intravenous injection of 500 microCi (37 megabecquerels) 125I-labeled metaiodobenzylguanidine (MIBG) 3 days before surgery. In the five control subjects, adrenal tumor uptake never exceeded the liver or spleen uptake. One patient with a negative preoperative MIBG scan demonstrated no intraoperative uptake. Five patients with pheochromocytoma had positive preoperative scans and in one other patient preoperative scanning was not done. In each of these six patients intraoperative count ratio of pheochromocytoma/liver from 14:2 to 250:16 and pheochromocytoma/contralateral adrenal ratio from 60:1.5 to 60:16 was demonstrated. An intraoperative scan in one of these patients detected two small metastatic tumor deposits previously overlooked by the surgeon after removing a larger mass that had been localized by a preoperative 131I-MIBG scan. A negative preoperative scan in one patient was followed by an intraoperative scan demonstrating a bone metastasis with a ratio of metastasis/normal bone of 10:0.5. Specimen studies demonstrated a significant MIBG uptake ratio of tumor/plasma ranging from 95 to 667 (average 404 +/- 242) greater than in control subjects (average 25 +/- 41); in the patient with metastasis the uptake ratio of metastasis/normal bone reached 98.4. We conclude that intraoperative 125I-MIBG scanning might detect pheochromocytoma deposits overlooked by preoperative 131I-MIBG scans.     

Surgical management of hereditary pheochromocytoma

BACKGROUND: Surgical treatment of hereditary pheochromocytoma remains controversial because of the need for lifelong corticosteroid therapy and the risk of Addisonian crisis associated with bilateral total adrenalectomy. We examined our large series of patients with hereditary pheochromocytoma to evaluate postsurgical outcomes, particularly in those who underwent cortical-sparing adrenalectomy. STUDY DESIGN: We retrospectively reviewed the outcomes of all patients with histopathologic diagnoses of hereditary pheochromocytoma treated at our institution from 1962 to 2003. Familial disease was initially determined by pedigree analysis, genetic testing, or both for multiple endocrine neoplasia (MEN) types 1, 2A, or 2B; von Hippel-Lindau disease (VHL); neurofibromatosis type 1 (NF-1); or familial paraganglioma syndrome (FP). RESULTS: Adrenal pheochromocytomas were present in 56 of 59 patients (95%): MEN2A (39), MEN2B (7), VHL (6), MEN1 (2), NF-1 (2). Paragangliomas (extraadrenal pheochromocytomas) were present in the remaining 3 of 59 patients (5%): FP (2) and NF-1 (1). Thirty-eight of 56 patients with pheochromocytomas had cumulative operations resulting in total or subtotal bilateral adrenalectomy. Acute adrenal insufficiency (Addisonian crisis) occurred in 4 of these 38 patients (11%). Cortical-sparing adrenalectomy was performed in 26 patients who underwent bilateral adrenal resection; 17 (65%) were corticosteroid independent at a median followup of 71 months. Recurrent pheochromocytoma developed in an adrenal remnant in 3 of 30 patients (10%) who underwent unilateral or bilateral cortical-sparing procedures. Metastatic disease did not develop in any patient with pheochromocytoma, but has occurred in two of three patients with paragangliomas. CONCLUSIONS: Our data suggest that a cortical-sparing adrenalectomy can successfully avoid the need for corticosteroid replacement in the majority of patients who undergo a bilateral adrenalectomy. Long-term followup should include monitoring of the remnant gland for recurrent pheochromocytoma with yearly biochemical screening studies.     

Pheochromocytoma associated with neurofibromatosis 1: a report of two cases

Pheochromocytomas may occur as either sporadic or familial tumors. Clinical features of pheochromocytomas in neurofibromatosis 1 (NF1) patients are similar to those in patients with sporadic pheochromocytomas, unlike pheochromocytomas associated with other hereditary syndromes. Here we report two cases of pheochromocytoma associated with NF1. Case 1: A 29-year-old man with previously undiagnosed NF1, was admitted to our hospital for hypertension and a right adrenal tumor. On physical examination, café-au-lait spots and neurofibromas were observed on his body. Serum and urine catecholamine levels were markedly elevated. Case 2: The patient was a 46-year-old man with NF1. The tumor was incidentally detected by ultrasonography. Serum and urine catecholamine levels were similarly elevated. 131I-MIBG scintigraphy showed an abnormal accumulation in the right adrenal gland. After this diagnosis of pheochromocytoma associated with NF1, open adrenalectomy was performed. No evidence of malignancy was seen in either case.     

Diagnosis and surgical treatment of adrenal tumors

Adrenal surgery is necessary for the management of functioning adrenal tumors, such as aldosterone-producing adenoma, cortisol-producing adenoma, and pheochromocytoma. The role of adrenal imaging in primary hyperaldosteronism is to separate the surgically resectable unilateral aldosteronoma from bilateral hyperplasia. Once the clinical diagnosis of primary hyperaldosteronism is confirmed, adrenal computed tomography (CT) with 3-mm sections should be the first imaging study. If the results of CT and NP-59 scintigraphy are equivocal, adrenal venous sampling is necessary. Cortisol-producing adrenocortical adenomas are seen as adrenal masses 2.5 cm or larger in diameter in CT scanning. When an adrenal mass measures more than 5 cm in diameter, a functioning adrenal carcinoma should be considered. Symptomatic pheochromocytomas are almost always 2 cm or larger. On MR scanning, pheochromocytomas are extremely bright on T2-weighted images. In patients with ectopic pheochromocytomas, 131I-MIBG scintigraphy should be mandatory. In the past decade, laparoscopic adrenalectomy has replaced open adrenalectomy as a standard operative procedure for benign adrenal tumors. Adrenal-sparing laparoscopic surgery has recently become a feasible option in patients with hereditary bilateral pheochromocytomas.     

Adrenalectomy for familial pheochromocytoma in the laparoscopic era

OBJECTIVE: To report the results of treatment of patients with familial pheochromocytomas in the laparoscopic era. SUMMARY BACKGROUND DATA: The optimal surgical management of pheochromocytomas that arise in familial neoplasia syndromes may be complicated by bilateral involvement and associated endocrinopathies. METHODS: Twenty-one patients with familial pheochromocytomas (15 with multiple endocrine neoplasia [MEN] 2A, 4 with MEN 2B, 1 each with von Hippel-Lindau and neurofibromatosis type 1) underwent adrenalectomy between December 1993 and July 2001. Clinical, biochemical, and pathologic data were obtained by retrospective review of perioperative medical records, postoperative biochemical testing, and patient questionnaire. RESULTS: Mean age at diagnosis was 37 +/- 11 years. Twenty of the 21 patients had elevated urine catecholamines, and all had radiographic evidence of an adrenal tumor or tumors. Pheochromocytoma-related symptoms were present in 11 patients (52%). One patient with MEN 2B underwent open adrenalectomy due to previous adrenal surgery and megacolon. Laparoscopic adrenalectomy was attempted in the remaining 20 patients (9 right, 11 left, 2 bilateral). Two patients (9.1%) were converted to open adrenalectomy. Intraoperative hypertensive episodes occurred in 15 patients (71%) and were easily controlled medically. Mean operative time was 216 +/- 57 minutes, mean postoperative length of stay was 3.1 +/- 1.3 days, and mean tumor size was 3.1 +/- 1.0 cm. Minor complications occurred in three patients (14.3%) and major complications in two patients (9.5%). During a mean follow-up of 57 months, a contralateral pheochromocytoma developed in four patients with MEN 2 (33%); three of them underwent adrenalectomy. There have been no long-term complications related to hypertension or adrenalectomy. CONCLUSIONS: This study is the largest series of patients with familial pheochromocytoma undergoing adrenalectomy during the laparoscopic era. The results suggest that the laparoscopic approach is safe and effective for managing unilateral or bilateral adrenal medullary disease in this population.     

Acute abdomen from ruptured adrenal pheochromocytoma: case report

The pheochromocytoma is a very rare neoplasm, which originates in 98% of cases in the adrenal medulla; it is often bilateral in familial syndromes. It is more frequent in syndromes like MEN2, von Hippel-Lindau disease, and neuofribromatosis type 1. In this article the Authors report a case of a young woman with a large adrenal pheochromocytoma, that presented by an acute abdomen; the treatment was explorative laparotomy with unilateral adrenalectomy. Therapy of this tumour is founded on surgery, plus chemiotherapy radiotherapy or treatment with 131I-MIBG (iodine-131-metaiodobenzylguanidine in malignant cases (10%). According with the absence of a correlation between pathological findings and clinical behaviour, a long-term follow up is indispensable.     

Persistenz eines primären Hyperaldosteronismus nach subtotaler Adrenalektomie

BACKGROUND: Primary aldosteronism is known to be caused by aldosterone-producing adenoma (APA).Total adrenalectomy is the standard procedure. In contrast to bilateral adrenal diseases (e.g., MEN II pheochromocytomas), there is no consensus about the effect of subtotal adrenalectomy. CASE REPORT: A 44-year-old patient with primary aldosteronism caused by APA underwent subtotal adrenalectomy including removal of one adenoma.Because hypertension and hypokalemia did not disappear and hyperaldosteronism persisted, the patient had to undergo reoperation in which the adrenalectomy was completed. DISCUSSION: Subtotal adrenalectomy in patients with Conn's syndrome is an interesting therapeutic option,whereas its effect is much higher in hereditary diseases of the adrenal gland.The benefit of preserved adrenal tissue has to be weighed against a possible persistence of hyperaldosteronism, especially in cases with normal opposite adrenal glands.     

Laparoscopic adrenal-sparing surgery: personal experience, review on technical aspects

Partial adrenalectomy is usually performed for the treatment of bilateral pheochromocytomas and in case of sporadic, monolateral tumors, to minimize the risk of adrenal failure, especially in younger patients. Due to the lack of consistent series, many issues such as correct surgical indications and technical aspects still need to be debated. From 2007 to 2010 we performed four unilateral partial adrenalectomies (3 aldosterone-producing adenomas and 1 cortisol-producing adenoma), and three bilateral subtotal adrenalectomies, consisting in total adrenalectomy on one side and partial adrenalectomy on the contralateral gland (3 bilateral pheochromocytomas in MEN IIa). In case of single tumor, partial adrenalectomy was carried out without adrenal vein ligation and the results were similar to total adrenalectomy both in terms of surgical and functional outcome, with normalization of hormone levels and control of hypertension. Operating time and postoperative stay were not significantly different from unilateral total adrenalectomy. In case of bilateral subtotal adrenalectomy our results demonstrate effectiveness in terms of surgical outcome and control of hypertension, but one patient needed steroid replacement therapy due to post-operative adrenocortical failure. Care must be taken when giving indication to adrenal sparing surgery, because this procedure can be technically difficult, and due to the risk of recurrence, especially in case of bilateral tumors, it can affect both surgical and functional outcomes.     

Simultaneous bilateral laparoscopic adrenalectomy for pheochromocytoma in multiple endocrine neoplasia (MEN) syndrome: Case report with review literature

INTRODUCTION

Laparoscopic adrenalectomy has gained favour as a preferred surgical approach in the multiple endocrine neoplasia (MEN) type 2 patients. Currently, there is limited literature on bilateral simultaneous laparoscopic adrenalectomy in MEN 2 syndrome. We reported two cases of bilateral pheochromocytoma associated with MEN 2 syndrome cured by simultaneous bilateral laparoscopic adrenalectomy.

PRESENTATION OF CASE

First patient presented with big lips since childhood and episodic abdominal pain. On investigations, he was diagnosed with features of MEN 2B syndrome. Second patient was hypertensive and presented with abdominal pain. On evaluation she had features of MEN 2A syndrome.

DISCUSSION

Minimally invasive approach was preferred in both cases. Bilateral simultaneous adrenalectomies were uneventfully done with acceptable operative time and blood loss with rapid perioperative recovery. These cases highlighted the feasibility of laparoscopic simultaneous bilateral adrenalectomy for pheochromocytomas in MEN 2 syndrome.

CONCLUSION

Laparoscopic simultaneous bilateral adrenalectomy is a safe feasible and preferable technique for pheochromocytomas associated with MEN 2 syndrome.     

Laparoscopic partial adrenalectomy for recurrent pheochromocytoma after open partial adrenalectomy in von Hippel-Lindau disease

BACKGROUND AND PURPOSE: Unilateral total adrenalectomy is the standard treatment for benign unilateral adrenal tumors. Partial adrenalectomy has to be considered for bilateral adrenal tumors. Recently, our group has reported the feasibility of unilateral and bilateral partial adrenalectomy by means of laparoscopy. Now, we present a case of recurrent pheochromocytoma after open bilateral adrenalectomy and demonstrate that laparoscopic cortex-sparing surgery is feasible for a recurrence after open surgery. Case Report: At the age of 10 years, a boy was found to have bilateral adrenal pheochromocytoma and was treated by open bilateral partial adrenalectomy. Eight years later, the patient presented with palpitation, sweating, and severe hypertension. Investigations biochemically and radiologically demonstrated functional recurrent pheochromocytoma in the left adrenal gland. Genetic studies confirmed mutation of the von Hippel-Lindau (VHL) gene. The patient was prepared for surgery preoperatively by phenoxybenzamine and metropolol. The surgery was performed as planned, and the normal adrenal tissue was spared. The patient had an uneventful postoperative course. His blood pressure was normal on the day of discharge. CONCLUSIONS: In a specialized center with experienced laparoscopic surgeons, laparoscopic partial adrenalectomy for recurrent pheochromocytoma is feasible even after previous open surgery on the ipsilateral adrenal gland. Adrenal-sparing surgery is indicated in hereditary syndromes such as VHL and MEN II to avoid the problems of life-long steroid replacement. Recurrences have to be expected, but further surgery may be less difficult by the previous laparoscopic approach.     

Giant cystic pheochromocytoma: a case report

The patient, a 59-year-old woman, was referred to our University Hospital for evaluation of a left mass. Ultrasonography revealed a left adrenal cystic mass. On excretory urograms, the left kidney was pressed downward by a suprarenal mass, and computerized tomography (CT) and magnetic resonance imaging (MRI) confirmed an adrenal cyst. 131I-meta-iodo-benzylguanidine (MIBG) scintigraphy showed prominent accumulation in the left adrenal mass and the capsule. Considering the elevation of catecholamines in both blood and urine samples, we performed a left adrenalectomy with a presumptive diagnosis of pheochromocytoma (tumor size: 11.6 x 7.5 x 6.5 cm, tumor weight 720 g). The subsequent pathological examination confirmed a left giant cystic pheochromocytoma. 131I-MIBG scintigraphy was the most useful tool in the diagnosis of the cystic pheochromocytoma.     

An operated case of multiple endocrine neoplasia type IIb and review of the Japanese literature

Multiple endocrine neoplasia, type IIb (MEN IIb) is a rare syndrome characterized by the occurrence of medullary thyroid carcinoma (MTC), pheochromocytoma and mucosal neuroma. A 35-year-old male patient with MEM IIb having megacolon, marfanoid habitus and no family history of the disease underwent surgery. Because MTC was present in both lobes, total thyroidectomy and modified neck dissection were performed. Pheochromocytoma was found bilaterally and bilateral adrenalectomy with adrenal autotransplantation in the rectus abdominis muscle was carried out. Postoperative course was satisfactory except for transient hypocalcemia and mild ileus. After the slow corticosteroid weaning process, his adrenocortical function was at the lower level within a normal range. In August 1986 (24 postoperative months), he was maintained by the administration of 10mg of hydrocortisone every three days, and calcitonin and CEA levels in sera were normal. We collected 15 cases reported in Japanese literatures. MTC and mucosal neuroma were found in all cases, whereas pheochromocytoma was present in 9 cases. Bilateral and multicentric occurrences were usual, and total thyroidectomy and bilateral adrenalectomy were, warranted. We believe that autotransplantation following bilateral adrenalectomy is a worthy alternative.     

Simultaneous bilateral laparoscopic adrenalectomy: a surgical option for multiple endocrine neoplasia (MEN 2) patients with bilateral pheochromocytomas

Multiple endocrine neoplasia (MEN 2) is a rare disorder. Of this group, 42% develop a pheochromocytoma of which 60% will have bilateral involvement. Although the benefits of unilateral laparoscopic adrenalectomy have been well documented, fewer cases of simultaneous bilateral laparoscopic adrenalectomy have been reported. We present the cases of three patients with MEN 2 who underwent successful simultaneous bilateral laparoscopic adrenalectomy after their initial presentation with bilateral pheochromocytoma. Although the management of bilateral pheochromocytomas has traditionally been approached via open laparotomy or bilateral posterior incisions, the bilateral laparoscopic approach should be considered a viable alternative for patients requiring surgical intervention. Clinical outcomes and complications are similar to open laparotomy. Simultaneous bilateral laparoscopic adrenalectomy is a safe and effective procedure that results in a more rapid recovery and a shorter hospital stay for patients with bilateral pheochromocytomas originating from MEN 2.     

Estimated risk of pheochromocytoma recurrence after adrenal-sparing surgery in patients with multiple endocrine neoplasia type 2A

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.