Lethality of Multiple Endocrine Neoplasia Type I

p < 0.02) or than all kindred members who did not die of MEN-I disease (median 55 years, p < 0.05). The causes of death of the MEN-I patients included islet cell tumor ( n = 12), ulcer disease ( n = 6), hypercalcemia/uremia ( n = 3), carcinoid tumor ( n = 6), and nonendocrine malignancies ( n = 9). There was no difference in survival between MEN-I carriers and unaffected kindred members. Of our MEN-I patients, 46% died from causes related to their endocrine tumors after a median age of 47 years, which was younger than family members who did not die from these tumors. Pancreatic islet cell tumors were the most common cause of death of MEN-I patients. Management of kindreds with MEN-I should include an aggressive screening program with early therapeutic intervention when a tumor is identified.     

Thymic Carcinoid Associated With Multiple Endocrine Neoplasia Syndrome Type I

Thymic carcinoids are a rare entity that may be associated with endocrine diseases like Cushing's syndrome or multiple endocrine neoplasia syndrome type I (MEN1). These tumors represent 4% of anterior mediastinal tumors and are characterized by their very aggressive behavior.We present the case of a patient with a previous MEN 1 diagnosis in whom, during the follow up of his disease, a thoracic image compatible with thymic carcinoid was detected. After an extended thymectomy that included peri-thymic fat resection, the clinical diagnosis was confirmed. A follow-up examination 14 months later revealed a suspicious lesion that suggested local recurrence, therefore the patient was reoperated on. The pathology report of this surgery indicated post-radiation fibrosis.Likewise, we present a review of the current diagnostic and therapeutic management of patients with MEN1 syndrome who are diagnosed with thymic carcinoid.     

Surgery for Asymptomatic Pancreatic Lesion in Multiple Endocrine Neoplasia Type I

n = 8, mean age 33 years) or symptomatic ( n = 12, mean age 51 years) stages of pancreatic endocrine involvement with the principal aim to evaluate postoperative morbidity, survival, and malignant potential of the pancreatic lesion. Radiologic signs of malignancy were not identified in any patient prior to exploration. All patients displayed multiple tumors with generally complex immunoreactivity. Normal postoperative pancreatic tumor markers were recorded in five of the asymptomatic patients, which became abnormal in three of them at a mean of 3 years after surgery. All patients remained without symptoms for a mean of 6 years after operation. In four symptomatic individuals (33%) metastases were identified at exploration, and two died with tumor; 83% of symptomatic patients displayed persistent or recurrent endocrine morbidity from the pancreatic lesion. Recognizing lead time bias, this limited and uncontrolled patient comparison suggests that exploration at the symptomatic stage of pancreatic involvement in MEN-I patients is unsatisfactory. Rather than to obtain biochemical cure, surgery in asymptomatic patients might be regarded as a means of cancer prevention. The malignancy of the pancreatic lesion may be preceded by several decades of biochemical abnormality. Extensive screening for this lesion allows diagnosis during adolescence and the timely application of primary exploration. Active management of individuals with repeated biochemical analyses followed by selective reintervention could enable satisfactorily maintained pancreatic functions and substantial duration of cancer prevention.     

多发性内分泌腺肿瘤

作者收治3例多发性内分泌腺肿瘤患者,包括肾上腺嗜铬细胞瘤,胰岛细胞瘤及垂体瘤,均行手术切除,病理证实诊断,治疗效果良好。结合国内外文献,对肾上腺合并的其他内分泌腺肿瘤的发病情况、临床分型、临床表现及治疗进行复习。     

Management of Pancreatic Endocrine Tumors in Multiple Endocrine Neoplasia Type 1

Introduction Pancreatic endocrine tumors (PETs) occur in at least 50% of patients with multiple endocrine neoplasia type 1 (MEN1) and are the leading cause of disease-specific mortality. However, the timing and extent of surgery for MEN1-related PETs is controversial owing to the indolent tumor growth seen in most patients and the desire to avoid complications associated with insulin dependence. To help resolve this controversy, we retrospectively analyzed the clinical characteristics, surgical treatment, and clinical outcome of patients with MEN1-related PETs. Methods All patients had histologic or radiographic confirmation of a PET in the setting of MEN1. Disease progression was defined radiographically as the development of new pancreatic tumors or distant metastases. Progression-free survival (PFS) and overall survival (OS) were used as the endpoints of this analysis. Results We identified 98 patients with MEN1, 55 (56%) of whom had PETs, including 27 women and 28 men with a median age of 37 years (range 8–69 years) at the time of diagnosis. Functioning PETs were present in 35 (64%) of 55 patients, and nonfunctioning tumors were present in 20 (36%). Pancreatic surgery was performed in 38 (69%) of the 55 patients; and the first operation included enucleation (n = 4), total pancreatectomy (n = 3), Whipple procedure (n = 4), and distal pancreatectomy (n = 27). The median size of the resected tumors was 2.8 cm (range 0.6–11.0 cm). Recurrent disease developed in the residual pancreas in 7 (20%) of 35 at-risk patients a median of 7.8 years after the first operation, and distant metastases occurred in 5 (14 %) of 36 surgically treated patients without distant metastasis (2 patients had distant metastases when surgery on the primary tumor was performed) at a median of 2.7 years following surgery. At last follow-up, 16 (29%) of 55 patients with PETs had died, 12 (22%) were alive with disease, 26 (47%) were alive without evidence of disease, and 1 (2%) was lost to follow-up. The median OS was 19.5 years (range 13–26 years) and was significantly longer for patients who had functioning PETs versus those with nonfunctioning tumors (P = 0.0007), for patients who underwent surgical resection of their PETs versus those who did not (P = 0.0043), and for patients with localized versus metastatic PETs at the time of diagnosis (P < 0.0001). Multivariate analysis revealed that younger age, hormonal function, and PET resection were independently associated with longer OS. Conclusions Our data suggest that early diagnosis and surgical excision of MEN1-related PETs improves survival. However, translating these data into a surveillance strategy for the early detection of PETs is complex owing to the potential morbidity of pancreatic resection and the risk of long-term insulin dependence.     

Intraoperative Parathormone Measurement in Patients with Multiple Endocrine Neoplasia Type I Syndrome and Hyperparathyroidism

Total or subtotal parathyroidectomy is considered the treatment of choice for multiple endocrine neoplasia type I (MEN-I)-associated primary hyperparathyroidism (HPT). However, persistent or recurrent HPT is frequently observed. The development of a rapid two-site immunoradiometric assay (IRMA) method for measuring intact parathormone (PTH) has provided a valuable tool for recognizing possible surgical failures. Our experience includes 16 MEN-I patients (10 females, 6 males) of mean age 35.5 years operated on between 1990 and 1996. Total parathyroidectomy (TPTX) with autotransplantation of parathyroid tissue was the standard treatment. Blood samples for PTH measurement were drawn at the induction of anesthesia (basal value), 10 and 20 minutes after the removal of each gland, and 60 minutes after TPTX. Rapid PTH measurement, which required only 15 minutes of incubation at 37°C, showed a highly significant correlation (p < 0.0001) with the standard method. Circulating PTH levels exhibited a stepwise decrease during TPTX, reaching a mean value of 22.3% of the baseline 20 minutes after removal of the last gland. Two patients showed a prompt decrease of PTH after removal of the single enlarged gland, featuring the kinetics observed in the adenomas. One of these two patients was successfully treated with more conservative surgery. None of the patients showed persistence or recurrence of HPT. In our experience, intraoperative measurement of PTH seems to be a valuable adjunct in both the diagnosis of multiglandular involvement and the prediction of surgical treatment in patients with primary parathyroid hyperplasia.     

The Multiple Endocrine Neoplasia syndromes

The Multiple Endocrine Neoplasia syndromes are familial disorders in which neoplastic changes develop in multiple endocrine tissues. Almost all of these diseases are inherited as autosomal dominant traits with complete penetrance but variable expressivity. Classification of the Multiple Endocrine Neoplasias is based on the pattern of endocrine organ involvement. Multiple Endocrine Neoplasia Type I (MEN-I) is characterized by the concurrence of pituitary adenomas, parathyroid hyperplasia and pancreatic islet cell neoplasms. Multiple Endocrine Neoplasia Type II (MEN-II or IIa) consists of medullary thyroid carcinoma (MTC), parathyroid hyperplasia and pheochromocytomas. Multiple Endocrine Neoplasia Type IIb (MEN-IIb) is similar to MEN-IIa in that affected patients have MTC and pheochromocytomas. Multiple mucosal neuromas and ganglioneuromatosis of the gastrointestinal tract are also present in patients with MEN-IIb, but these individuals rarely manifest hyperparathyroidism. The Multiple Endocrine Neoplasia syndromes have attracted a great deal of attention because of their characteristic clinical features and familial pattern of occurrence. By utilizing recently developed "provocative tests" it is possible through aggressive screening of kindred members at risk to detect certain of these diseases (particularly MTC and pancreatic islet cell neoplasia) at an early stage. Therapeutic intervention in selected patients is associated with a high cure rate.     

Multiple Endocrine Neoplasia Type 1 Parathyroid Adenoma Development over Time

Multiple gland parathyroid disease is one of the hallmarks of multiple endocrine neoplasia (MEN) type 1. Often mislabeled parathyroid hyperplasia, the process is actually the development of multiple adenomas. Some clinicians have reported results of selective parathyroidectomy in this group, removing only grossly enlarged glands. We argue that all the glands are at risk and should be addressed at any planned parathyroid intervention. Our hypothesis is that, given sufficient time, patients would all develop adenomas in each of the parathyroid glands. Our available data to address this issue are the parathyroidectomy results from a single institution series. Patients who had initial parathyroid exploration for hyperparathyroidism in the setting of MEN-1 were reviewed. This study includes those patients who had the weights of the resected glands documented; 23 men and 21 women met the criteria. The total weight of the parathyroid glands did not vary with the age of the patient at operation. However, the number of normal glands identified did vary significantly with age (p < 0.02), with older patients being less likely to have any normal parathyroid glands. Although total parathyroid weight may correlate with development of hypercalcemia and indications for operation, the involvement of multiple parathyroid glands in MEN-1 is a function of time, as independent events in each gland must occur. Given time, MEN-1 patients all develop multiple gland disease, and this reality must be used in planning operative management for patients with this syndrome.This article was presented at the International Association of Endocrine Surgeons meeting, Uppsala, Sweden, June 14–17, 2004.     

Limited Value of Ga-68-DOTATOC-PET-CT in Routine Screening of Patients with Multiple Endocrine Neoplasia Type 1

Background

Routine screening is recommended for patients with multiple endocrine neoplasia type 1 (MEN1) to enable early detection and treatment of associated neuroendocrine neoplasms (NEN). Gallium⁶⁸-DOTATOC-Positron emission tomography combined with computed tomography (Ga-68-DOTATOC-PET-CT) is a very sensitive and specific imaging technique for the detection of sporadic neuroendocrine tumors. The present study evaluated the value of Ga-68-DOTATOC-PET-CT in routine screening of patients with MEN1.

Methods

Between January 2014 and March 2016, all MEN1 patients underwent Ga-68-DOTATOC-PET-CT in addition to conventional imaging (computed tomography of the thorax, magnetic resonance imaging of the abdomen and pituitary, endoscopic ultrasonography). The diagnostic yield of conventional imaging and Ga-68-DOTATOC-PET-CT was prospectively documented and compared, and treatment changes caused by the addition of Ga-68-DOTATOC-PET-CT were recorded.

Results

Conventional imaging detected 145 NENs, mainly pancreaticoduodenal NENs (n = 117, 81%), in 31 of 33 MEN1 patients. Ga-68-DOTATOC-PET-CT detected 55 NENs in 23 of the 33 patients (p = 0.0001). Ninety (62%) NENs detected by conventional imaging were missed by DOTATOC-PET-CT. The majority of missed lesions were pNEN (n = 68; 74%). The sensitivity of Ga-68-DOTATOC-PET-CT for NENs <5, 5–9, 10–19 and ≥20 mm was 0, 29, 81 and 100%, respectively. However, Ga-68-DOTATOC-PET-CT detected more liver and lymph node metastases in patients with known metastatic disease, which did not lead to a change of patients’ management. In one patient (3%), Ga-68-DOTATOC-PET-CT was the only imaging modality that detected a small intestine NEN and led to potentially curative surgery.

Conclusion

Ga-68-DOTATOC-PET-CT cannot be recommended for routine screening of MEN1 patients. It might provide important additional information in patients with suspected or known metastatic disease.

     

Familial Hyperparathyroidism without Multiple Endocrine Neoplasia

n = 4) or recurrent ( n = 3) hyperparathyroidism. Three patients (19%) also had papillary thyroid cancer, and 7 (44%) had other coexistent thyroid disorders. Among 51 patients with FHPT reported in the literature, 23 (45%) had serum calcium ≥ 3.75 mmol/L, and 23 (45%) had multiple abnormal parathyroid glands; 10 (20%) had recurrent hyperparathyroidism. FHPT without other endocrinopathies is a distinct entity. Patients with FHPT have multiple abnormal parathyroid glands and are prone to both recurrent and persistent hyperparathyroidism. They frequently present with profound hypercalcemia or hypercalcemic crisis, in contrast to patients with MEN-associated hyperparathyroidism or sporadic hyperparathyroidism.     

Prophylactic Surgery for Multiple Endocrine Neoplasia Type IIa after Genetic Diagnosis: Is Parathyroid Transplantation Indicated?

RET proto-oncogene predisposing to multiple endocrine neoplasia type IIa (MEN-IIa) has allowed a DNA-based approach to diagnosis and treatment by prophylactic thyroidectomy in children testing genetically positive. Although total thyroidectomy is the accepted operation for C cell disease, the necessity of routine total parathyroidectomy and autotransplantation as previously described in these asymptomatic children is questionable, particularly given the low occurrence of hyperparathyroidism in MEN-IIa (10–20%). Thirty-six children (ages 1 month to 12 years) from four MEN-IIa kindreds at risk for disease underwent genetic testing. Mutational analysis was done using a highly sensitive PCR-based denaturing gradient gel electrophoresis technique. Parathyroid or serum calcium concentrations were determined preoperatively. Of the 36 children at risk, 18 were found to have a MEN-IIa mutation; 11 have undergone prophylactic thyroidectomy at ages ranging from 2 to 12 years (mean 7.5 years). In each case, there was no biochemical evidence of hypercalcemia preoperatively, and all parathyroid glands were identified and were found to be grossly normal at exploration. Glands were carefully dissected and left in situ. Postoperatively, 10 of the 11 children maintained normocalcemia, allowing discharge within 24 to 36 hours. Resected thyroid glands contained C cell hyperplasia in nine, medullary carcinoma in one, and normal histology in one. We conclude that an alternative to routine parathyroidectomy may be desirable for prophylactic treatment of MEN-IIa. In situ parathyroid preservation can be safely achieved without compromising the completeness of the thyroid resection. This conservative approach obviates the potential morbidity associated with total parathyroidectomy and autotransplantation.     

Primary Hyperparathyroidism in Multiple Endocrine Neoplasia Type IIa: Retrospective French Multicentric Study

n = 2), 1 ( n = 24), 2 ( n = 5), > 2 ( n = 12), 4 ( n = 11). Pathology (initial surgery) consisted of 24 adenomas, 4 double adenomas, and 25 hyperplasia. Cure after initial surgery was obtained in 89%, including a 22% incidence of hypoparathyroidism. There were 6 cases (11%) with persistent PHPT. With a mean follow-up of 6.4 years, five patients (9%) had recurrent PHPT. The results indicate that MEN-IIa-related PHPT is generally associated with mild, often asymptomatic hypercalcemia. Despite recurrences encountered 5 to 15 years after the first cervicotomy, resection of only macroscopically enlarged glands generally appears sufficient. Subtotal or total parathyroidectomy with autotransplantation is associated with a high rate of hypoparathyroidism.     

Bronchial Carcinoid and Type 1 Multiple Endocrine Neoplasia Syndrome. A Case Report

Carcinoid tumours of bronchial origin are rare in type 1 multiple endocrine neoplasia (MEN1) syndrome. The prevalence of histologically confirmed cases is approximately 5–8%, although in more recent studies it is estimated that it could be much higher and a possible relationship with the presence of hypergastrinaemia is suggested. We report a patient with a type 1 MEN syndrome, with no respiratory symptoms, with hypergastrinaemia, and in whom a 5 mm diameter nodule was detected in the wall of the left main bronchus by computed tomography. The bronchial biopsy confirmed that it was a typical bronchial carcinoid and the octreoscan showed a single focus of high uptake coinciding with this lesion. A bronchoplastic (sleeve) was performed with extirpation of 3 bronchial rings, which also demonstrated that it was a typical carcinoid.     

Unilateral Clearance for Primary Hyperparathyroidism in Selected Patients with Multiple Endocrine Neoplasia Type 1

Background

Primary hyperparathyroidism is the most common manifestation of multiple endocrine neoplasia type 1 (MEN1). Guidelines advocate subtotal parathyroidectomy (STP) or total parathyroidectomy with autotransplantation due to high prevalence of multiglandular disease; however, both are associated with a significant risk of permanent hypoparathyroidism. More accurate imaging and use of intraoperative PTH levels may allow a less extensive initial parathyroidectomy (unilateral clearance, removing both parathyroids with cervical thymectomy) in selected MEN1 patients with primary hyperparathyroidism.

Methods

We performed a retrospective cohort study at a high-volume tertiary medical center including patients with MEN1 and primary hyperparathyroidism, who underwent STP or unilateral clearance as their initial surgery from 1995 to 2015. Unilateral clearance was offered to patients who had concordant sestamibi and ultrasound showing a single enlarged parathyroid gland. For both the groups, we compared rates of persistent/recurrent disease and permanent hypoparathyroidism.

Results

Eight patients had unilateral clearance and 16 had STP. Subtotal parathyroidectomy patients were younger (37 vs 52 years). One patient in each group had persistent disease. One (13 %) unilateral clearance and five (31 %) STP patients had recurrent hyperparathyroidism after a mean follow-up of 47 and 68 months (p = 0.62). No unilateral clearance patients and two of 16 SPT patients had permanent hypoparathyroidism (p = 0.54).

Conclusions

Some MEN1 patients with primary hyperparathyroidism who have concordant localizing studies may be selected for unilateral clearance as an alternative to STP. For appropriately selected MEN1 patients, unilateral clearance can achieve similar results as STP and has no risk of permanent hypoparathyroidism, and may facilitate possible future reoperations.

     

Screening of Patients with Multiple Endocrine Neoplasia Type 1 (MEN-1): A Critical Analysis of Its Value

Background  Screening of multiple endocrine neoplasia type 1 (MEN-1) patients is widely recommended because one-fifth succumb to malignant neoplasms. However, recommendations for screening modalities and intervals are based mostly on nonprospective data. Methods  Thirty-five of 48 MEN-1 patients were evaluated at least twice by an annual screening program in a single-center, prospective, nonrandomized study between 1997 and 2006. The screening program comprised anamnesis, clinical examination, imaging procedures, and extensive biochemical evaluations. Prospectively diagnosed lesions were evaluated separately from nonprospectively diagnosed lesions at first evaluation. Results  The median age of the patients was 45 years (range = 15–70) at initial assessment. They were followed for a median of 72 months (range = 24–108) by a median of 6 (range = 2–10) evaluations. The vast majority of lesions were nonprospectively diagnosed at initial evaluation: 13 of 17 patients had primary hyperparathyroidism (pHPT), 24 of 29 had pancreatic endocrine tumors (PETs), and 4 of 4 had carcinoids. Vice versa adrenal lesions were mostly prospectively detected (18/23). Malignancy was observed in 10 patients (28%) in the initial assessment and without symptoms in 5 patients (9 PETs, 3 carcinoids). Endoscopic ultrasound (EUS) of 29 patients detected 88 PETs which were followed for 157 patient years. The mean annual growing rate was 13.28 ± 28.23 mm with respect to the baseline tumor diameter of 9 mm. In 35 patients the mean incidence of newly diagnosed PETs was 0.52/year. Adrenal lesions were invariably nonfunctional. A mean change in diameter of 6.7 ± 23.44% was monitored and malignant transformation was absent. Conclusions  Most lesions are detected at initial screening, particularly malignant tumors. Computed tomography of the abdomen and chest did not identify additional lesions. The interval between screenings could be extended to 3 years based on annually calculated growth rates and the incidence of MEN-1-associated lesions. The assessment of calcium, gastrin, and prolactin is sufficient for biochemical screening in MEN-1.     

Ultrasonography Should Not Guide the Timing of Thyroidectomy in Pediatric Patients Diagnosed with Multiple Endocrine Neoplasia Syndrome 2A through Genetic Screening

Background

American Thyroid Association (ATA) guidelines suggest that thyroidectomy can be delayed in some children with multiple endocrine neoplasia syndrome 2A (MEN2A) if serum calcitonin (Ct) and neck ultrasonography (US) are normal. We hypothesized that normal US would not exclude a final pathology diagnosis of medullary thyroid cancer (MTC).

Methods

We retrospectively queried a MEN2A database for patients aged <18 years, diagnosed through genetic screening, who underwent preoperative US and thyroidectomy at our institution, comparing preoperative US and Ct results with pathologic findings.

Results

35 eligible patients underwent surgery at median age of 6.3 (range 3.0–13.8) years. Mean MTC size was 2.9 (range 0.5–6.0) mm. The sensitivity of a US lesion ≥5 mm in predicting MTC was 13 % [95 % confidence interval (CI) 2 %, 40 %], and the specificity was 95 % [95 % CI 75 %, 100 %]. Elevated Ct predicted MTC in 13/15 patients (sensitivity 87 % [95 % CI 60 %, 98 %], specificity 35 % [95 % CI 15 %, 59 %]). The area under the receiver operating characteristic curve (AUC) for using US lesion of any size to predict MTC was 0.50 [95 % CI 0.33, 0.66], suggesting that US size has poor ability to discriminate MTC from non-MTC cases. The AUC for Ct level at 0.65 [95 % CI 0.46, 0.85] was better than that of US but not age [AUC 0.62, 95 % CI 0.42, 0.82].

Conclusions

In asymptomatic children with MEN2A diagnosed by genetic screening, preoperative thyroid US was not sensitive in identifying MTC of any size and, when determining the age for surgery, should not be used to predict microscopic MTC.     

Primary Hyperparathyroidism in Multiple Endocrine Neoplasia Type 1: Individualized Management With Low Recurrence Rates

Background To evaluate the outcomes in different surgical modalities for primary hyperparathyroidism in multiple endocrine neoplasia type 1 (MEN1) patients, intraoperative findings from a single surgeon were studied to investigate a potentially improved modality of parathyroidectomy (PTx). Methods All 22 patients had PTx by a single surgeon in the past 21 years. Three modalities of PTx were used, depending on the operative findings, after all parathyroids and the thymus were identified. If fewer than three glands were enlarged, selective removal of the enlarged glands with or without biopsy of a normal-appearing gland was performed (selective PTx); if all glands were enlarged, either a subtotal PTx leaving a 50-mg remnant in situ or a total PTx with autotransplantation (TPTx + AT) was performed. Results There were 7 men and 15 women, aged 22 to 67 years (average, 43 years). Sixteen had familial and six had sporadic MEN1. They underwent 23 operations, including 11 selective PTx, 6 subtotal PTx, and 6 TPTx + AT. On follow-up for 1 to 19 years, only one patient (4.6%) had recurrent hyperparathyroidism 5.5 years after subtotal PTx. Others had either normocalcemia (n = 14; 63.6%) or hypocalcemia (n = 7; 31.8%). Those who had either a subtotal PTx or TPTx + AT had a significantly higher rate of postoperative hypocalcemia than those who had a selective PTx (9.9% vs. 54.5%; P = .032; Fisher’s exact test). Conclusions Primary hyperparathyroidism in our MEN1 patients was less aggressive than that reported in the literature. Selective PTx according to the intraoperative findings achieved optimal outcomes.     

Prospective Evaluation of Imaging Procedures for the Detection of Pancreaticoduodenal Endocrine Tumors in Patients with Multiple Endocrine Neoplasia Type 1

Early identification of pancreaticoduodenal endocrine tumors (PETs) in multiple endocrine neoplasia type 1 (MEN-1) is mandatory, because these tumors represent the most common cause of death within the syndrome. The diagnostic value of imaging procedures has therefore been evaluated in a prospective observational study. Between December 1997 and June 2003 twenty-two MEN-1 patients with genetically confirmed disease were followed for PETs using a standardized screening program with serum hormone measurements, endoscopic ultrasonography (EUS), computed tomography (CT), and somatostatin-receptor scintigraphy (SRS). Results could be validated by surgery and histopathology in 13 patients during 18 operations. In 12 asymptomatic patients with tumors measuring 10 mm or less, who have not yet undergone operation, PETs were detected by EUS in 12/12, by CT in 1/12, and by SRS in 2/11 cases. In 13 patients who have undergone surgical exploration EUS, CT, and SRS were true positive in 12 of 16, 7 of 13, and 12 of 17 cases, respectively, although the number of tumors detected by each imaging procedure alone was lower than the number detected intraoperatively and histopathologically in almost every case. A solitary liver metastasis in one patient and a nonfunctioning PET recurrence in another were identified only by SRS. Endoscopic untrasonography is the most sensitive imaging procedure for the detection of small ( 10 mm) PETs in MEN-1, whereas SRS is the procedure of choice for the identification of metastases of MEN-1 PETs—i.e., for staging. Detection of PETs at an early stage by an aggressive screening program using EUS may lead to prompt surgical intervention and improved prognosis of MEN-1 PETs.This article was presented at the International Association of Endocrine Surgeons meeting, Uppsala, Sweden, June 14–17, 2004.