Metastatic pheochromocytoma associated with multiple endocrine neoplasia syndrome type II.

Pheochromocytoma is a rare adrenal medullary tumor of chromaffin cell origin that presents a syndrome of alpha- and beta-adrenergic receptor stimulation due to secretion of epinephrine and norepinephrine. This tumor occurs sporadically in the population and is also associated with multiple endocrine neoplasia syndrome type II (MEN II). Although malignant pheochromocytoma is associated with sporadic tumors, those associated with familial MEN syndromes are rarely malignant. We report a case of a rare metastatic pheochromocytoma in a patient with MEN IIA. Surgical debulking, which has been shown to benefit many patients with metastatic neuroendocrine tumors, was attempted in this patient. Palliation, with symptom relief, was provided. The options for treatment of metastatic pheochromocytoma are discussed.     

Medullary thyroid carcinoma and pheochromocytoma accompanied with nodular hyperplasia in multiple endocrine neoplasia type 2

Three patients with familial multiple endocrine neoplasia type 2 underwent total adrenalectomy and subsequently near-total or total thyroidectomy. The overt pheochromocytomas were present bilaterally in two patients and unilaterally in another patient. In addition, multiple nodules measuring a few mm in diameter were demonstrated in all adrenal medullas examined. All patients exhibited bilateral medullary thyroid carcinomas which varied in size from a few minute nodules accompanied by the microscopic C-cell hyperplasia to distinct large tumors. The thyroid C-cell hyperplasia appeared to be confined to the upper and middle thirds of the lateral lobe, and micronodules of the C-cell hyperplasia enlarged to coalesce, forming one large carcinoma mass. On the other hand, nodular hyperplasia of the chromaffin cells was distributed diffusely throughout the adrenal medulla and each nodule appeared to develop individually into a large pheochromocytoma. These findings suggested that, at least in the family members at a high risk for multiple endocrine neoplasia type 2, the development of both medullary thyroid carcinoma and pheochromocytoma was always preceded by a multicentric nodular hyperplasia. On the basis of the pathogenesis of these tumors, the most rational surgical approach was presented. Presented at the 14th Annual Congress of the Japan Society for Cancer Therapy, Sendai, September 30, 1976.     

Medullary thyroid carcinoma and pheochromocytoma accompanied with nodular hyperplasia in multiple endocrine neoplasia type 2

Three patients with familial multiple endocrine neoplasia type 2 underwent total adrenalectomy and subsequently near-total or total thyroidectomy. The overt pheochromocytomas were present bilaterally in two patients and unilaterally in another patient. In addition, multiple nodules measuring a few mm in diameter were demonstrated in all adrenal medullas examined. All patients exhibited bilateral medullary thyroid carcinomas which varied in size from a few minute nodules accompanied by the microscopic C-cell hyperplasia to distinct large tumors. The thyroid C-cell hyperplasia appeared to be confined to the upper and middle thirds of the lateral lobe, and micronodules of the C-cell hyperplasia enlarged to coalesce, forming one large carcinoma mass. On the other hand, nodular hyperplasia of the chromaffin cells was distributed diffusely throughout the adrenal medulla and each nodule appeared to develop individually into a large pheochromocytoma. These findings suggested that, at least in the family members at a high risk for multiple endocrine neoplasia type 2, the development of both medullary thyroid carcinoma and pheochromocytoma was always preceded by a multicentric nodular hyperplasia. On the basis of the pathogenesis of these tumors, the most rational surgical approach was presented.     

Laparoscopic surgery in patients with sporadic and multiple insulinomas associated with multiple endocrine neoplasia type 1

There have recently been reports of a limited number of laparoscopic procedures in patients with clinically manifest hyperinsulinism. However, the precise role of laparoscopy remains unknown. Between January 1998 and September 2003, 11 consecutive patients (10 women and 1 man; mean age, 40 years; age range, 22–66 years) with sporadic insulinoma and two female patients (25 and 40 years old) with multiple insulinomas associated with multiple endocrine neoplasia type 1 (MEN-1) were operated on using the laparoscopic approach. Endoscopic ultrasonography was used to localize the tumor preoperatively in 90% of patients with sporadic insulinoma. In patients with MEN-1, computed tomography and octreoscan-111In demonstrated multiple tumors. Laparoscopic ultrasonography (LapUS) was performed in all patients for operative decision-making. Of 11 patients with sporadic insulinoma, laparoscopic enucleation (LapEn) was planned in 8 patients, but in 1 patient, the use of LapUS missed the tumor and the patient was converted to open surgery. Mean operating time after LapEn (seven patients) was 180 minutes, and the mean blood loss was 200 ml. The mean hospital stay was 5 days. In three of the 11 patients, laparoscopic spleen-preserving distal pancreatectomy (LapSPDP) was performed; the mean operative time was 240 minutes, and the mean blood loss was 360 ml. Postoperative complications occurred in three of seven patients after LapEn (three pancreatic fistulas managed conservatively, and one case of bleeding requiring reoperation). LapSPDP was performed in both patients with MEN-1; in one patient with splenic vessel preservation (SVP), the operating time was 210 minutes and blood loss was 650 ml, with a hospital stay of 6 days. In another patient without SVP, the operating time was 150 minutes and blood loss was 300 ml. The latter patient developed a 4-cm splenic infarct managed conservatively, and the hospital stay was 14 days. LapEn and LapSPDP are feasible and safe and achieved cure in patients with sporadic insulinoma and multiple insulinomas associated with MEN-1. However, the risk of pancreatic leakage after LapEn remains high, and LapSPDP without SVP may be associated with splenic infarct.     

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.     

Duodenopancreatic resections in patients with multiple endocrine neoplasia type 1

OBJECTIVE: To review the authors' 7-year experience with a surgical approach for pancreatic and duodenal neuroendocrine tumors (NETs) in patients with multiple endocrine neoplasia type 1 (MEN 1) designed to remove all gross tumor with limited complications, preserving pancreatic function. SUMMARY BACKGROUND DATA: MEN 1 is an autosomal dominant familial neoplasia syndrome characterized by the development of NETs of the duodenum and pancreas. Some tumors are clinically insignificant or follow a benign course, although a subset pursues a malignant, lethal natural history; the risk of surgical management must be appropriate to the disease course. METHODS: The clinical, biochemical, genetic, and pathologic data were retrospectively reviewed for 21 consecutive MEN 1 patients undergoing pancreatic resection for NETs between 1993 and 1999 at one institution. Age at operation, presenting symptoms, results of preoperative and intraoperative localization studies, major and minor complications, and pathology, including metastases, were analyzed. RESULTS: The surgical approach was selected based on the location and size of the tumors. Five patients required pancreaticoduodenectomy, 11 patients underwent non-Whipple pancreatic resections, and 5 underwent simple enucleation of benign NETs. The incidence of regional lymph node metastases was 33%. CONCLUSIONS: Major pancreatic procedures can be performed safely in most patients with MEN 1 and NETs. Because NETs are the most common MEN 1-related cause of death in the authors' kindreds, an aggressive surgical approach, including early intervention before malignant spread and major pancreatic resection where indicated, appears justified.     

Prominent corneal nerves in patients with multiple endocrine neoplasia type 2A: Diagnostic implications

We examined corneal nerves of 22 patients from 10 families with multiple endocrine neoplasia type 2A (MEN-2A). According to the findings in slit-lamp biomicroscopic examination and photographic documentation, the increased visibility of corneal nerves were classified into 5 grades (Grade 0=invisible to Grade 4=as thick as in MEN-2B). All eyes of normal subjects, 19 of 20 eyes of patients with anterior keratoconus, and 11 of 12 eyes of patients with non-hereditary medullary thyroid carcinoma (MTC) were either grade 0 or 1, and the remaining 2 eyes were evaluated as grade 2. Of the 44 eyes of MEN-2A patients, 5 (11.4%) eyes were grade 0, 11 (25%) eyes were grade 1, 19 (43.2%) eyes were grade 2, 8 (18.2%) eyes were grade 3, and 1 (2.3%) eye was grade 4. Thus, more than 60% of eyes of MEN-2A patients showed pathologically thickened corneal nerves of varying degree (grade 2 or higher). There was no definite relationship between the grade of corneal nerve thickening and the patient's age or presence of pheochromocytoma. Differences in the grade of corneal nerve thickening were observed among affected members belonging to the same MEN-2A family, but unaffected members of the family never showed prominent corneal nerves of grade 2 or higher. Our findings suggest that MTC patients with thickened corneal nerves might actually be MEN-2A patients and should be carefully followed for other components of this syndrome.

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Resumen La presencia de nervios corneanos prominentes es un hallazgo constante en casos de neoplasia endocrina múltiple tipo 2B (NEM 2B). Recientemente encontramos un paciente con NEM 2A y nervios corneanos prominentes, lo cual nos indujo a estudiar la incidencia del engrosamiento de los nervios corneanos en los pacientes con NEM 2A. Examinamos los nervios de 22 pacientes provenientes de 10 familias con alto riesgo de NEM 2A. Según los hallazgos en el examen biomicroscópico con la lámpara de hendidura y la documentación fotográfica, la apariencia aumentada de los nervios corneanos fue clasificada en 5 grados (Grado 0=invisibles, Grado 4=tan gruesos como en el NEM 2B). La totalidad de los ojos en los individuos normales, 19 de 20 ojos en pacientes con queratocono anterior y 11 de 12 ojos de pacientes con carcinoma medular no hereditario de la glándula tiroides (CMT) fueron grado 0 o 1, y los 2 ojos restantes fueron clasificados como grado 2. De los 44 ojos de los pacientes con NEM 2A, 5 (11.4%) fueron grado 0, 11 (25%) grado 1, 19 (43.2%) grado 2, 8 (18.2%) grado 3 y 1 (2.3%) grado 4. O sea, que más de 60% de los ojos de los pacientes con NEM 2A demostró engrosamiento patológica de los nervios corneanos de grado variable (Grado 2 o más alto). No se halló relación definitiva entre el grado del engrosamiento y la edad del paciente o la presencia de feocromocitoma. Se observaron diferencias en cuanto al grado de engrosamiento entre los miembros afectados de una misma familia con NEM 2A, pero los miembros no afectados no exhibieron prominencia grado 2 o mayor de los nervios. Nuestros hallazgos sugieren que pacientes con CMT y engrosamiento de los nervios corneanos pueden realmente tener NEM 2A y que deben ser seguidos cuidadosamente para investigar la presencia de otros componentes de este síndrome.

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Résumé Nous avons examiné les nerfs cornéens chez 22 patients issus de 10 familles à haut risque de MEN 2A. Suivant les résultats de l'examen biomicroscopique à la lampe à fente et les clichés photographiques, l'augmentation de la visibilité des nerfs cornéens a été classée en 5 grades (grade 0=invisible, grade 4=aussi épais que lors de la MEN 2B). Les yeux de tous les sujets normaux, 19 sur 20 yeux des patients avec antécédent de kératite et 11 des 12 yeux des patients ayant un carcinome médullaire de la thyroïde non héréditaire (MTC) étaient de grade 0 ou 1 et les 2 yeux restants étaient évalués de grade 2. Sur les 44 yeux des patients atteints de MEN 2A, 5 yeux (11.4%) étaient classés grade 0, 11 yeux (25%) grade 1, 19 yeux (43.2%) grade 2, 8 yeux (18.2%) grade 3 et 1 oeil (2.3%) grade 4. C'est-à-dire que plus de 60% des yeux des patients atteints de MEN 2A présentaient des nerfs cornéens anormalement épaissis à des degrés variables (grade 2 ou plus). Nos résultats suggèrent que les patients atteints de MTC qui présentent un épaississement des nerfs cornéens peuvent être en réalité atteints de MEN 2A et doivent être soigneusement suivis à la recherche d'autres anomalies de ce syndrome.

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Presented at the International Association of Endocrine Surgeons in Stockholm, Sweden, August, 1991.     

Presymptomatic screening for medullary thyroid carcinoma in patients with multiple endocrine neoplasia type 2A

Presymptomatic screening of medullary thyroid carcinoma in MEN IIA families enables the early diagnosis of this tumor with its significant morbidity. Biochemical screening consists of basal and stimulated serum calcitonin evaluation. Genetic screening is based on DNA analysis using linked DNA markers. Thyroidectomy at an occult tumor stage may be curative. Calcitonin measurement was carried out in 58 apparently unaffected family members at risk and 11 MEN IIA patients. Calcitonin elevation was detected in nine individuals. All nine underwent thyroidectomy. Histologic examination confirmed medullary thyroid carcinoma in eight patients and in one case C cell hyperplasia. Postoperatively, eight patients (89%) are clinically and biochemically tumor-free (mean follow-up 30 months). DNA screening results in one affected family are presented. DNA analysis allowed recognition of one apparently unaffected individual at risk as a MEN IIA gene carrier. One family member at risk was found not to carry the gene and may be excluded from further screening.

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Resumen El tamizaje presintomático del carcinoma medular de la glándula tiroides en familias con síndrome NEM 2A hace posible el diagnóstico precoz de este tumor, el cual en forma característica se asocia con significativa morbilidad. El tamizaje bioquímico consiste en la determinación de los niveles calcitonina sérica basal y estimulada. El tamizaje genético se basa en el análisis de ADN utilizando marcadores ligados al ADN. La tiroidectomía que se realiza cuando el tumor es todavía clínicamente oculto puede ser curativa. La determinación de calcitonina fue realizada en 58 familiares aparentemente no afectados pero de reconocido riesgo y en 11 pacientes con síndrome NEN 2A; se detectó calcitonina elevada en 9 individuos, y todos los nueve fueron sometidos a tiroidectomía. El examen histológico confirmó carcinoma medular en 8 e hiperplasia de células C en 1. Postoperatoriamente 8 pacientes (89%) se hallan clínica y bioquimicamente libres de tumor (promedio del seguimiento, 30 meses). Se presentan los resultados del tamizaje de ADN en una familia afectada. El análisis de ADN permitió el reconocimiento de un individuo aparentemente no afectado pero de riesgo como portador del gen NEM 2A. Un familiar con riesgo fue marcado como no portador del gen y puede ser excluído de tamizajes ulteriores.

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Résumé Le dépistage du cancer médullaire de la thyroïde avant l'apparition des symptômes dans les familles MEN 2A facilite le diagnostic de cette maladie accompagnée d'une morbidité non négligeable. Le dépistage biochimique consiste en une évaluation de la calcitonine basale et stimulée. Le dépistage génétique comporte une analyse de l'ADN qui utilise des marqueurs spécifiques des liaisons d'ADN. La thyroïdectomie a des chances d'être curative au stade de tumeur occulte. La calcitonine a pu ètre mesurée chez 58 membres d'une famille atteinte mais sans symptômes et chez 11 patients MEN 2A. La calcitonine était élevée chez 9. Tous ces patients ont eu une thyroïdectomie et un cancer médullaire a été retrouvé chez 8 et une hyperplasie des cellules C chez le neuvième. Postopérativement, 8 patients (89%) sont sans tumeur clinique et biologique (suivi moyen: 30 mois). Les résultats du dépistage par l'ADN chez une famille atteinte sont présentés et a permis d'identifier un seul membre apparemment non symptomatique qui était à risque de porter le gêne MEN 2A. On a déterminé également qu'un membre n'était pas porteur du gêne; il peut être exclu de tout examen de dépistage ultérieur.

     

Predictive DNA testing and prophylactic thyroidectomy in patients at risk for multiple endocrine neoplasia type 2A.

BACKGROUND: Missense germ-line mutations in the RET protooncogene are associated with multiple endocrine neoplasia type 2A (MEN 2A). Detection of these mutant alleles in kindred members predicts disease inheritance and provides the basis for preventative thyroidectomy. METHODS: A polymerase chain reaction (PCR)-based genetic test for the 19 known RET mutations was designed to study 132 members of 7 kindreds with MEN 2A. Haplotypes also were constructed using genetic markers flanking the MEN 2A locus. Plasma calcitonin (CT) concentrations were determined before and after provocative testing. RESULTS: Direct DNA testing and haplotype analysis showed that 21 of 58 kindred members at risk for disease had inherited a mutation in the RET protooncogene associated with MEN 2A. Plasma CT concentrations were elevated in 9 of the 21 family members, but were normal in 12. After genetic counseling, 13 of the 21 kindred members (6 with normal and seven with elevated plasma CT levels), consented to immediate thyroidectomy. In each patient, the resected thyroid gland showed C-cell hyperplasia with or without medullary thyroid carcinoma. There were no metastases to regional lymph nodes, and postoperative stimulated plasma CT levels were normal. CONCLUSION: The PCR-based direct DNA test for RET mutations is accurate, rapid, and reproducible. For all 132 individuals evaluated, the results of direct DNA analysis were consistent with haplotype studies. The direct test for mutations in the RET protooncogene is the preferred method for screening MEN 2A kindreds. In family members who have inherited a RET mutation, total thyroidectomy is indicated, regardless of the plasma CT values.     

Gastrointestinal manifestations of multiple endocrine neoplasia type 2

OBJECTIVE: To determine the clinical features, natural history, and role of surgery for gastrointestinal manifestations of the multiple endocrine neoplasia type 2 (MEN 2) syndromes. SUMMARY BACKGROUND DATA: The MEN 2 syndromes are characterized by medullary thyroid carcinoma and other endocrinopathies. In addition, some patients with MEN 2A develop Hirschsprung's disease (HD), and all patients with MEN 2B have intestinal neuromas and megacolon that can cause significant gastrointestinal problems. METHODS: From 83 families with MEN 2A, eight patients with HD were identified (MEN 2A-HD). These and all patients with MEN 2B followed at the authors' institution (n = 53) were sent questionnaires to describe the onset and type of gastrointestinal symptoms and treatment they had before the diagnosis of MEN 2. Records of all patients responding were reviewed, including radiographic imaging, histology, surgical records, and genetic testing. RESULTS: Thirty-six of the 61 patients (59%) responded (MEN 2A = 8, MEN 2B = 28) to the questionnaires. All patients with MEN 2A-HD were operated on for HD 2 to 63 years before being diagnosed with MEN 2. All patients responding were underweight as infants and had symptoms of abdominal pain, distention, and constipation. Eighty-eight percent had hematochezia, 63% had emesis, and 33% had intermittent diarrhea before surgery. All patients with MEN 2A-HD had rectal biopsies with a diverting colostomy as the initial surgical procedure. This was followed by a colostomy takedown and pull-through procedure at a later interval. Ninety-three percent of patients with MEN 2B had gastrointestinal symptoms 1 to 24 years before the diagnosis of MEN 2. Symptoms included flatulence (86%), abdominal distention or being underweight as a child (64%), abdominal pain (54%), constipation or diarrhea (43%), difficulty swallowing (39%), and vomiting (14%). Seventy-one percent of patients with MEN-2B with gastrointestinal symptoms had radiographic imaging, 32% were admitted to the hospital, and 29% underwent surgery. CONCLUSIONS: Patients with MEN 2A-HD had a typical HD presentation and always required surgery. Patients with MEN 2B have significant gastrointestinal symptoms, but less than a third had surgical intervention. Understanding the clinical course and differences in these patients will improve clinical management.     

Differences between sporadic pheochromocytoma and pheochromocytoma in multiple endocrime neoplasia, type 2

We studied the gross and microscopic pathology of the adrenal gland in 69 cases of sporadic phenochromocytoma in order to develop a profile of the neoplasm to compare with that of pheochromocytoma observed in the syndrome of multiple endocrine neoplasia, type 2 (MEN 2). The results showed that sporadic pheochromocytoma was a unicentric (93%), unilateral (100%) neoplasm, which was associated with normal extratumoral adrenal medulla (100%). The findings contrast with those encountered in the adrenal gland in MEN 2, in which the tumor involvement is frequently multicentric, usually bilateral, and associated with extratumoral medullary hyperplasia in cases of early involvement. Therefore, the interpretation of the results of pathologic examination of a pheochromocytoma should be immediately communicated to the surgeon.     

Metastasectomy of neuroendocrine tumors in patients with multiple endocrine neoplasia type 1

Background

Neuroendocrine (NE) tumors commonly afflict patients with multiple endocrine neoplasia type 1 (MEN1). It is thought that patients with MEN1 have improved survival compared with individuals with analogous lesions. The role of metastasectomy of NE tumors in MEN1 patients is not clearly defined.

Methods

A review of MEN1 patients undergoing surgery for NE tumors from 1994 to 2010 at a single tertiary care center was performed. Tumor function, the extent of metastasis, R0 resection, and survival were analyzed.

Results

We identified 30 patients who underwent resection including synchronous and metachronous metastasectomy. Synchronous metastases were identified in 19 patients (63%), whereas 11 (37%) had metachronous disease. R0 resection was achieved in 93% of patients. Estimated 10-year survival is 86.4% (95% confidence interval, 60% to 100%) with no factors predictive of overall survival. The disease-free interval at 1, 5, and 10 years was 89%, 50%, and 19%, respectively, with recurrence occurring at a median of 5.4 years (95% confidence interval, 77.7% to 100%). Synchronous metastasis (P = .0072; hazard ratio [HR], 3.4) and nonfunctioning tumors (P = .014; HR, 3.3) were more likely to recur, whereas age (P = .09; HR, 1.5), gender (P = .49; HR, 1.3), and the site of metastasis (P = .81; HR, 1.1) did not influence recurrence.

Discussion

Patients with MEN1 benefit from resection of metastatic NE disease. Despite a high recurrence rate, survival and disease-free interval is favorable vs patients without MEN1.     

Outcome of duodenopancreatic resections in patients with multiple endocrine neoplasia type 1

OBJECTIVE: To evaluate the outcome of an aggressive surgical approach for duodenopancreatic neuroendocrine tumors (PETs) associated with multiple endocrine neoplasia type 1 (MEN1). SUMMARY BACKGROUND DATA: The management of PETs is still controversial in the setting of the autosomal dominant inherited MEN1 syndrome. METHODS: MEN1 patients that had either biochemical evidence of functioning PETs or visualized nonfunctioning PETs larger than 1 cm in size on imaging were operated. Since 1997, patients were followed annually by biochemical testing and imaging studies. RESULTS: Twenty-six genetically confirmed MEN1 patients underwent duodenopancreatic resection for functioning (n = 17) or nonfunctioning (n = 9) PETs. Ten (38%) patients had malignant PETs as characterized by the presence of lymph node (10 patients) and/or distant metastases (2 patients). The surgical approach was selected based on the type, location, and size of PETs. Four Zollinger-Ellison syndrome (ZES) patients required pylorus preserving pancreaticoduodenectomy (PPPD) as initial or redo procedure, 20 patients underwent other duodenopancreatic resections, and 2 patients had simple enucleations of PETs. After median 83 months (range, 5-241 months), 24 patients were alive and 2 patients died of an unrelated cause. All patients with insulinoma or vipoma and 7 of 11 patients with ZES were biochemically cured, including the ZES patients who underwent PPPD. However, 19 of 26 (73%) patients developed new small PETs (<1 cm) in the pancreatic remnant, but no patient had yet detectable metastases on imaging. CONCLUSIONS: Early and aggressive surgery of PETs in MEN1 patients prevents the development of liver metastases, which are the most life-threatening determinant. PPPD might be the procedure of choice for MEN1-ZES, which has to be proven in large scale studies.     

Surgical treatment of hyperparathyroidism in patients with multiple endocrine neoplasia type 1

HYPOTHESIS: Three-gland parathyroidectomy with trans-cervical thymectomy and cryopreservation is the preferred initial surgical approach for hyperparathyroidism (HPT) in patients with multiple endocrine neoplasia type 1. DESIGN: Retrospective cohort study. SETTING: Tertiary referral center. PATIENTS: Thirty-seven patients with multiple endocrine neoplasia type 1 who underwent 1 or more surgical procedures for HPT from January 1, 1973 to April 30, 2004. RESULTS: At initial parathyroid surgery, 16 (43%) of 37 patients had fewer than 3 parathyroid glands resected (group 1); 16 (43%) had at least 3 but fewer than 4 glands (group 2), and 5 (14%), 4 or more glands (group 3). Follow-up of at least 6 months after initial surgery was complete for 31 (84%) of 37 patients. CONCLUSIONS: Recurrent HPT in patients with multiple endocrine neoplasia type 1 is frequent if fewer than 3 glands are removed at initial parathyroidectomy. Optimal surgical intervention must balance the risk of recurrent hypercalcemia with the morbidity of permanent hypoparathyroidism. Three-gland parathyroidectomy, transcervical thymectomy, and parathyroid cryopreservation constitute our preferred initial surgical procedure.     

Subtotal adrenalectomy for phaeochromocytoma in multiple endocrine neoplasia type 2A.

OBJECTIVE: To describe our surgical technique for, and results of, subtotal adrenalectomy for phaeochromocytoma in multiple endocrine neoplasia (MEN) type 2. DESIGN: Retrospective study. SETTING: Teaching hospital, The Netherlands. SUBJECTS: 6 patients (four women and 2 men, mean age 35 years, range 31-46) with MEN type 2 who presented between 1993 and 1996. INTERVENTIONS: Cortical sparing adrenalectomy (n =4) together with contralateral total adrenalectomy in bilateral disease (n = 2). MAIN OUTCOME MEASURES: Morbidity, mortality, adrenal function postoperatively, and recurrence. RESULTS: Cortical sparing adrenalectomy leaving adequate adrenal reserve was possible in all cases. There was no operative morbidity or mortality. Mean follow-up was 40 months (range 1347). One patient developed a recurrent phaeochromocytoma 24 months after subtotal adrenalectomy. CONCLUSIONS: Subtotal adrenalectomy with preservation of adequate adrenal cortical reserve was feasible in all cases. Long term follow-up is necessary to establish its definitive place in the treatment of familial phaeochromocytoma.     

Laparoscopic resection of periadrenal paraganglioma in a patient with multiple endocrine neoplasia type 2A

We report here a case of recurrent pheochromocytoma successfully managed by laparoscopic surgery in a patient with multiple endocrine neoplasia type 2A. A 25-year-old man presented with the contralateral adrenal mass after earlier right adrenalectomy. For the preoperative diagnosis of left adrenal pheochromocytoma, adrenal sparing surgery was considered. From the intraoperative laparoscopic view, we found that the tumor originated in periadrenal sympathetic ganglia, and laparoscopic excision of paraganglioma was successfully performed that preserved the integrity of normal adrenal gland. Extra-adrenal pheochromocytoma is rather rare in MEN 2A and it is important to identify precise intraoperative localization of pheochromocytoma with laparoscopic surgery.