Multiple endocrine neoplasia type 4 (MEN4): a thorough update on the latest and least known men syndrome.

PURPOSE: Multiple endocrine neoplasia type 4 (MEN4) is a rare multiglandular endocrine neoplasia syndrome, associated with a wide tumor spectrum but hallmarked by primary hyperparathyroidism, which represents the most common clinical feature, followed by pituitary (functional and non-functional) adenomas, and neuroendocrine tumors. MEN4 clinically overlaps MEN type 1 (MEN1) but differs from it for milder clinical features and an older patient's age at onset. The underlying mutated gene, CDKN1B, encodes the cell cycle regulator p27, implicated in cellular proliferation, motility and apoptosis. Given the paucity of MEN4 cases described in the literature, possible genotype-phenotype correlations have not been thoroughly assessed, and specific clinical recommendations are lacking. The present review provides an extensive overview of molecular genetics and clinical features of MEN4, with the aim of contributing to delineate peculiar strategies for clinical management, screening and follow-up of the last and least known MEN syndrome. METHODS: A literature search was performed through online databases like MEDLINE and Scopus. CONCLUSIONS: MEN4 is much less common that MEN1, tend to present later in life with a more indolent course, although involving the same primary organs as MEN1. As a consequence, MEN4 patients might need specific diagnostic and therapeutic approaches and a different strategy for screening and follow-up. Further studies are needed to assess the real oncological risk of MEN4 carriers, and to establish a standardized screening protocol. Furthermore, a deeper understanding of molecular genetics of MEN4 is needed in order to explore p27 as a novel therapeutic target.

Multiple endocrine neoplasia in a sheep: insulinoma, adrenocortical carcinoma with myxoid differentiation, and thyroid C-cell carcinoma.

An ~10-y-old male sheep had anorexia and progressive weight loss for ~1 mo. The sheep was emaciated, and 20 d later, became recumbent and lethargic, and was hypoglycemic (0.33 mmol/L; RI: 2.6-4.4 mmol/L). The sheep was euthanized because of poor prognosis, and submitted for autopsy. We found no gross lesions in the pancreas; however, histologically, focal proliferations of round-to-polygonal cells were separated by connective tissue into small nests. These proliferating cells, which had abundant eosinophilic-to-amphophilic cytoplasm and hyperchromatic nuclei, were immunopositive for insulin and negative for glucagon and somatostatin; the lesion was diagnosed as an insulinoma. Insulinoma has not been reported previously in sheep, to our knowledge. In addition, autopsy and histologic examination revealed the presence of an adrenocortical carcinoma with myxoid differentiation and a thyroid C-cell carcinoma. Our case indicates that multiple endocrine neoplasms can occur in sheep, as in other animal species.

[Primary lymph node gastrinoma]. / Gastrinoma primario de ganglio linfático.

Gastrinomas are neuroendocrine tumors usually located in the duodenum and pancreas, in the context of a Multiple Endocrine Neoplasm and forming a Zollinger-Ellison syndrome. The location of this type of lymph node tumor is extremely unusual and its early diagnosis constitutes a real challenge to be able to establish an adequate treatment and manage the complications that these entail. We present the case of a 64-year-old male patient with a lymph node gastrinoma and whose surgical removal resulted in the immediate remission of the patient's symptoms.

Long delay in diagnosis of a case with MEN1 due to concomitant presence of AIMAH with insulinoma: a case report and literature review.

BACKGROUND: ACTH-independent macronodular hyperplasia (AIMAH) is an uncommon disorder characterized by massive enlargement of both adrenal glands and hypersecretion of cortisol. Concomitant AIMAH and multiple endocrine neoplasia type1 (MEN1) is rare to our knowledge. CASE PRESENTATION: Herein, we describe a 32 year old woman with long history of prolactinoma and secondary ammonhrea presented with not-severe manifestation of hypoglycemia due to concomitant presence of insulinoma with AIMAH leading to 12 years delay of MEN1 diagnosis. Laboratory tests showed severe hypoglycemia associated with hyper insulinemia (non-fasting blood sugar = 43 mg/dl, insulin = 80.6 µIU /ml, C-peptide = 9.3 ng/ml) hyperparathyroidism (calcium = 10.3 mg/dl, phosphor = 3.1 mg/dl, PTH = 280 pg/ml) and chemical evidence of an ACTH-independent hypercortisolism (serum cortisol value of 3.5, after 1 mg dexamethasone suppression test serum ACTH value of 17 pg/ml, and high urinary cortisol level). Abdominal CT scan demonstrated two enhancing well-defined masses 27*20 mm and 37*30 mm in the tail and body of the pancreas, respectively, and a 36*15 mm mass in left adrenal gland (seven Hounsfield units). Dynamic pituitary MRI revealed a partial empty sella. The physical examination of the patient was unremarkable. Distal pancreatectomy and a left adrenalectomy were performed. After the surgery, we observed clinical and biochemical remission of hyper insulinemia and gradual decrease in urinary cortisol. The histological features of the removed left adrenal gland were consistent with AIMAH. Histological examination of the pancreatic lesions revealed well differentiated neuroendocrine tumors. Genetic abnormalities in the MEN1, heterozygote for pathogenic variant chr11; 645,773,330-64577333AGAC, c.249-252delGTCT, p. (11e85Serfs Ter33) in exon 2 were found. It was recommended the patient undergoes parathyroidectomy as soon as possible. CONCLUSION: Given the history and presentation of our case, we recommend that the clinicians consider the possibility of autonomous cortisol production in MEN1 patients who do not show severe symptoms of hypoglycemia in the presence of insulinoma.

Case Report: New CDKN1B Mutation in Multiple Endocrine Neoplasia Type 4 and Brief Literature Review on Clinical Management.

Background: The fourth type of multiple endocrine neoplasia (MEN) is known as a rare variant of MEN presenting a MEN1-like phenotype and originating from a germline mutation in CDKN1B. However, due to the small number of cases documented in the literature, the peculiar clinical features of MEN4 are still largely unknown, and clear indications about the clinical management of these patients are currently lacking. In order to widen our knowledge on MEN4 and to better typify the clinical features of this syndrome, we present two more cases of subjects with MEN4, and through a review of the current literature, we provide some possible indications on these patients' management. Case Presentation: The first report is about a man who was diagnosed with a metastatic ileal G2-NET at the age of 34. Genetic analysis revealed the mutation p.I119T (c.356T>C) of exon 1 of CDKN1B, a mutation already reported in the literature in association with early-onset pituitary adenomas. The second report is about a 76-year-old woman with a multifocal pancreatic G1-NET. Genetic analysis identified the CDKN1B mutation c.482C>G (p.S161C), described here for the first time in association with MEN4 and currently classified as a variant of uncertain significance. Both patients underwent biochemical and imaging screening for MEN1-related diseases without any pathological findings. Conclusions: According to the cases reported in the literature, hyperparathyroidism is the most common clinical feature of MEN4, followed by pituitary adenoma and neuroendocrine tumors. However, MEN4 appears to be a variant of MEN with milder clinical features and later onset. Therefore, these patients might need a different and personalized approach in clinical management and a peculiar screening and follow-up strategy.

Phosphate Metabolism and Pathophysiology in Parathyroid Disorders and Endocrine Tumors.

The advent of new insights into phosphate metabolism must urge the endocrinologist to rethink the pathophysiology of widespread disorders, such as primary hyperparathyroidism, and also of rarer endocrine metabolic bone diseases, such as hypoparathyroidism and tumor-induced hypophosphatemia. These rare diseases of mineral metabolism have been and will be a precious source of new information about phosphate and other minerals in the coming years. The parathyroid glands, the kidneys, and the intestine are the main organs affecting phosphate levels in the blood and urine. Parathyroid disorders, renal tubule defects, or phosphatonin-producing tumors might be unveiled from alterations of such a simple and inexpensive mineral as serum phosphate. This review will present all these disorders from a 'phosphate perspective'.

Multiple Endocrine Neoplasia: Spectrum of Abdominal Manifestations.

OBJECTIVE. Multiple endocrine neoplasia (MEN) syndromes are autosomal-dominant genetic disorders that predispose two or more organs of the endocrine system to tumor development. Although the diagnosis relies on clinical and serologic findings, imaging provides critical information for surgical management with the ultimate goal of complete tumor resection. CONCLUSION. This article reviews abdominal neoplasms associated with the various subtypes of MEN syndromes, with a focus on clinical presentation and characteristic imaging features.

Synchronous detection of SDHA-related gallbladder paraganglioma and pancreatic neuroendocrine tumor.

Primary gallbladder paragangliomas (PGLs) are exceedingly rare. PGLs are extraadrenal neuroendocrine tumors that are morphologically inseparable from intraadrenal pheochromocytomas. PGLs and pheochromocytomas are some of the most heritable tumor types in the body and are often associated with other tumors or part of a genetic syndrome. We report a case of gallbladder PGL presenting synchronously with pancreatic neuroendocrine tumor (NET) and pulmonary IgG4-related disease in a 74-year old male patient with disseminated prostate adenocarcinoma. Due to the high rate of germline mutations and the possible syndromal manifestation of PGLs as well as pancreatic NETs, this patient was offered genetic testing, and a pathogenic SDHA germline mutation was found. Immunohistochemically, there was loss of SDHA and SDHB in the PGL but neither in the NET nor in the prostate adenocarcinoma. To our knowledge, this case is the first report of gallbladder PGL associated with pancreatic NET. It is likely that the identified SDHA germline mutation played a role in the development of gallbladder PGL in this patient.

Germline CDKN1B Loss-of-Function Variants Cause Pediatric Cushing's Disease With or Without an MEN4 Phenotype.

CONTEXT: Germline loss-of-function CDKN1B gene variants cause the autosomal dominant syndrome of multiple endocrine neoplasia type 4 (MEN4). Even though pituitary neuroendocrine tumors are a well-known component of the syndrome, only 2 cases of Cushing's disease (CD) have so far been described in this setting. AIM: To screen a large cohort of CD patients for CDKN1B gene defects and to determine their functional effects. PATIENTS: We screened 211 CD patients (94.3% pediatric) by germline whole-exome sequencing (WES) only (n = 157), germline and tumor WES (n = 27), Sanger sequencing (n = 6), and/or germline copy number variant (CNV) analysis (n = 194). Sixty cases were previously unpublished. Variant segregation was investigated in the patients' families, and putative pathogenic variants were functionally characterized. RESULTS: Five variants of interest were found in 1 patient each: 1 truncating (p.Q107Rfs*12) and 4 nontruncating variants, including 3 missense changes affecting the CDKN1B protein scatter domain (p.I119T, p.E126Q, and p.D136G) and one 5' untranslated region (UTR) deletion (c.-29_-26delAGAG). No CNVs were found. All cases presented early (10.5 ± 1.3 years) and apparently sporadically. Aside from colon adenocarcinoma in 1 carrier, no additional neoplasms were detected in the probands or their families. In vitro assays demonstrated protein instability and disruption of the scatter domain of CDKN1B for all variants tested. CONCLUSIONS: Five patients with CD and germline CDKN1B variants of uncertain significance (n = 2) or pathogenic/likely pathogenic (n = 3) were identified, accounting for 2.6% of the patients screened. Our finding that germline CDKN1B loss-of-function may present as apparently sporadic, isolated pediatric CD has important implications for clinical screening and genetic counselling.

Identification of Occult Adenomas in Primary Hyperparathyroidism With 18F-fluorocholine PET/CT. / Identificación de adenomas ocultos en hiperparatiroidismo primario con PET-TC 18F-fluorocolina.

INTRODUCTION: Single parathyroid adenomas are the most common cause of primary hyperparathyroidism (PHP) in our population. Parathyroidectomy is still the only potentially curative treatment and requires preoperative localization imaging studies to perform selective surgery. In patients with negative results on conventional tests, PET/CT has demonstrated higher sensitivity rates. METHODS: A prospective cohort study was designed, including 34 patients diagnosed with PHP between 2017 and 2019, candidates for surgery with negative preoperative localization tests with scintigraphy and MIBI SPECT/CT. All patients underwent PET/CT with 18F-Fluorocholine. The clinical, biochemical and postoperative outcome results were compared with a control group of 30 patients with positive standard tests. RESULTS: Hyperfunctional parathyroid tissue was detected in 85% of the patients that had undergone choline PET/CT. The selective resection of the adenoma identified in these patients achieved curative criteria in 87% of the cases without undergoing bilateral cervical surgical exploration. The preoperative levels of PTH, calcemia and gland weight were significantly lower in this group compared to the control group. No differences were identified in cure criteria or approach between the 2groups. CONCLUSION: In our study, choline PET/CT showed higher detection rates compared to the gold standard. The increase provides the opportunity to perform unilateral selected adenoma resection, especially in patients with smaller adenomas associated with lower calcemia and PTH levels and patients with previous cervical surgery.

[Inherited tumor syndromes of gastroenteropancreatic and thoracic neuroendocrine neoplasms]. / Syndromes de prédisposition aux tumeurs neuroendocrines gastro-entéro-pancréatiques et thoraciques.

About 5% of gastroenteropancreatic and thoracic neuroendocrine neoplasms (NENs) arise in the context of an inherited tumour syndrome. The two most frequent syndromes are: multiple endocrine neoplasia type 1 (MEN1), associated with a large spectrum of endocrine and non endocrine tumours, including duodenopancreatic, thymic and bronchial NENs, and the von Hippel-Lindau syndrome VHL, associated with pancreatic NENs. Two inherited syndromes have a low incidence of NENs: neurofibromatosis type 1 (NF1), associated with duodenal somatostatinomas, and tuberous sclerosis (TSC), associated with pancreatic NENs. Two rare syndromes have a high incidence of NENs: multiple endocrine neoplasia type 4 (MEN4), with a tumour spectrum similar to that of MEN1, and glucagon cell hyperplasia neoplasia (GCHN), involving only the pancreas. It is likely that other syndromes remain to be characterized, especially in familial small-intestinal NENs. The diagnosis is usually raised because of the suggestive clinical setting: young age at diagnosis, multiple tumours in multiple organs, familial history. Except in VHL and NF1, tumours themselves do not show specific pathological features; they usually are well differentiated and of low histological grade; their prognosis is good, except for MEN1-associated thymic NENs. The most suggestive pathological feature is their combination with various endocrine and/or non endocrine lesions in the adjacent tissue. Pathological examination is important, for a correct diagnosis and for an accurate management of the patients and their families, who must be referred to expert centers.

Atypical ovarian carcinoid tumor with widespread skeletal metastases: a case report of multiple endocrine neoplasia type 1 in a young woman.

BACKGROUND: Multiple endocrine neoplasia type 1 (MEN1) is a rare autosomal dominant inherited condition affecting multiple endocrine organs, resulting in significant morbidity and decreased life expectancy. Early tumor identification allows for timely patient management, reduces morbidity, and improves disease outcomes. Patients with MEN1 typically present with primary hyperparathyroidism caused by multiple parathyroid tumors, however, thymic and bronchial carcinoid tumors are also less common manifestations. MEN1-related neuroendocrine tumors often show hematogenous metastasis, with the liver being the most common metastatic site. Skeletal metastases from neuroendocrine tumors are extremely rare. As few as 50 case reports were identified in a recently published literature review on skeletal metastases from carcinoid tumors. To our knowledge, studies related to MEN1 have not been previously conducted. CASE PRESENTATION: We present a case of MEN1-related atypical ovarian carcinoid presenting as the first disease manifestation in a 30-year old woman. After two years, another atypical carcinoid was incidentally diagnosed in the contralateral ovary during a caesarean section. Syndromic MEN1 was not diagnosed clinically despite her young age and bilateral involvement. The patient remained disease-free for two years without further adjuvant treatment prior to clinic presentation with complaints of chest discomfort and body pain. Radiologic and pathologic investigations identified multifocal simultaneous neuroendocrine tumors involving the parathyroid, thymus, pancreas, and adrenal glands, in addition to multiple other metastatic sites. The findings ultimately resulted in the patient being diagnosed with MEN1. CONCLUSIONS: This extremely rare case emphasizes that ovarian carcinoids, especially when bilateral, could be the initial manifestation of MEN1. The significance of this differential diagnosis was highlighted by the subsequent detection of widespread skeletal metastasis resulting from the carcinoid tumors. A low threshold of suspicion, systemic diagnostic work-up, and regular follow-up are of utmost importance to timely diagnosis of MEN1.

Clinical Features of Multiple Endocrine Neoplasia Type 4: Novel Pathogenic Variant and Review of Published Cases.

CONTEXT: The clinical phenotype of multiple endocrine neoplasia type 4 (MEN4) is undefined due to a limited number of published cases. Knowledge on disease manifestation in MEN4 is essential for developing prevention programs and treatment. OBJECTIVE: To expand current knowledge of the MEN4 phenotype including assessment of penetrance. DESIGN: This is a case report and a brief review of previously published MEN4 cases. PATIENTS: We report a large Danish family with multiple cases of endocrine tumors that segregated with a pathogenic variant in the CDKN1B gene. MAIN OUTCOME/RESULT: The medical history of the proband included primary hyperparathyroidism and Cushing disease. Genetic analysis identified a pathogenic variant in CDKN1B (c.121_122delTT, p.Leu41Asnfs*83). Among the family members, another 12 individuals were identified as carriers of the same variant, which segregated with development of endocrine tumors. Hypercalcemia due to primary hyperparathyroidism occurred in all 13 of the available carriers of the genetic variant, and 4 patients also had functioning or nonfunctioning pituitary adenomas, whereas 1 patient had a metastatic neuroendocrine tumor (carcinoid). Loss-of-heterozygosity was detected in two of five parathyroid adenomas, supporting that CDKN1B acts as a tumor suppressor gene. Thirty cases representing 16 different CDKN1B variants have previously been reported, and these cases presented primarily with primary hyperparathyroidism and functioning and nonfunctioning pituitary tumors. CONCLUSION: Hypercalcemia due to primary hyperparathyroidism and pituitary tumors are common in MEN4. Gastrointestinal neuroendocrine tumors appear to be less prevalent in MEN4 than in MEN1.

CT- and ultrasound-characteristics of hepatic lesions in patients with multiple endocrine neoplasia syndrome. A retrospective image review of 25 cases.

INTRODUCTION: Liver metastases from neuroendocrine tumors in multiple endocrine neoplasia syndrome are common (75%) and significantly impairs the prognosis. Characterisation of liver lesions in these patients is challenging, as liver metastases are difficult to differentiate from benign liver lesions such as haemangioma. METHODS: In this study we aimed to characterize the radiological findings of hepatic metastases in MEN patients. The findings of contrast-enhanced CT were considered for the main diagnosis. We retrospectively evaluated 25 patients with MEN-syndrome (10 MEN1/ 15 MEN2) including 11 men and 14 women between 28-62 years of age. RESULTS: Liver metastases (48%, 12/25) and hemangioma (40%, 10/25) were the most common liver lesions among our patients. The most common primary tumors in our MEN1 and MEN2 patients with liver metastases were of pancreatic neuroendocrine tumor (70%, 7/10) und medullary thyroid carcinoma (100%, 15/15) origin, respectively. CT-characteristics were grouped into three main categories, depending on contrast dynamics. The majority of hepatic metastases (75%, 14/25) are presented as multiple lesions with a slow growth in an average 5 years of follow-up-period. We were able to find a common CT pattern and categorise these for each MEN-syndrome. Hepatic metastases in MEN1 presented commonly a blurred arterial enhancement with a low portal venous enhancement and less frequently a prominent enhancement in the arterial phase, which mimics the classical haemangioma. In MEN2 the liver metastases exhibited disseminated mixed hyper- and hypo-enhanced lesions in CT-scans. Moreover, lesion calcifications are pathognomonic in MEN2. The main limitation of this study is the missing histopathological confirmation in the majority of cases. CONCLUSIONS: In this retrospective imaging study, we were able to categorise and find a common CT pattern for hepatic lesions in patients with MEN-syndrome. In order to differentiate these lesions sufficiently, a combination of a 3-phasic CT-scan with US is required. Other liver specific imaging modalities (MRI, CEUS, SMS-PET/CT) should complement the diagnosis in individual cases.

Multiple endocrine neoplasia-like syndrome in 24 baboons (Papio spp.).

Multiple endocrine neoplasia (MEN) has not been reported in baboons, but this condition is well described in humans. An internal database was searched for all cases of concurrent endocrine hyperplasia and neoplasia in baboons. Twenty-four baboons (Papio spp.) with concurrent endocrine hyperplasia and neoplasia were identified. Twenty-one baboons had lesions in two endocrine organs, two baboons had lesions in three organs, and one baboon had lesions in four organs. Ten baboons aligned with the MEN1 classification; 14 baboons did not match any current human MEN classification. We report 24 cases of MEN-like syndrome in baboons. MEN1-like lesions accounted for nearly half (41%) of the affected animals. Genetic analysis of baboons with MEN-like syndrome could further elucidate the mechanisms of MEN and support the use of baboons as animal models for human MEN.

Insulinoma: A retrospective study analyzing the differences between benign and malignant tumors.

BACKGROUND/OBJECTIVES: Insulinoma is a rare pancreatic tumor and, usually, a benign disease but can be a malignant one and, sometimes, a highly aggressive disease. The aim of this study was to determine differences between benign and malignant tumors. METHODS: Retrospective study of 103 patients with insulinoma treated in a tertiary center. It was analyzed demographic, clinical, laboratory, localization and histologic analysis of tumor and follow up data of subjects in order to identify differences between individuals benign and malignant disease. RESULTS: Almost all patients (87%) had a benign tumor and survival rates of 100% following pancreatic tumor surgery. Those with malignant tumors (13%) have a poor prognosis, 77% insulinoma-related deaths over a period of 1-300 months after the diagnosis with a survival rate of 24% in five years. The following factors are associated with an increased risk of malignant disease: duration of symptoms < 24 months, fasting time for the occurrence of hypoglycemia < 8 h, blood plasma insulin concentration ≥ 28 µU/mL and C-peptide ≥ 4.0 ng/mL at the glycemic nadir and tumor size ≥ 2.5 cm. CONCLUSIONS: Our data help to base the literature about these tumors, reinforcing that although insulinoma is usually a single benign and surgically treated neoplasia, the malignant one is difficult to treat. We highlight the data that help predict a malignancy behavior of tumor and suggest a long follow up after diagnosis in these cases.

Case report of 18 F-fluorodeoxyglucose positron emission tomography-computed tomography imaging of a patient with multiple endocrine gland metastases from small cell lung cancer.

Synchronous multiple endocrine gland metastasis caused by small cell lung cancer (SCLC) is rare. A patient was investigated for primary cancer because of suspected brain metastasis on computed tomography (CT). Baseline 18 F-fluorodeoxyglucose (FDG) positron emission tomography (PET)-CT was positive in the lung and multiple endocrine glands (right thyroid, right breast, pancreatic body, right adrenal gland, and left ovary). Histopathology confirmed small cell lung cancer. The patient's symptoms were alleviated after chemotherapy and brain radiotherapy. Follow-up PET-CT revealed that some of the lesions had disappeared and some had reduced in size. This rare case of multiple endocrine gland metastases from SCLC suggests that whole body PET-CT is a useful tool to detect rare/asymptomatic metastases.

Medullary Thyroid Carcinoma: Prognostic Variables And Tumour Markers Affecting Survival.

BACKGROUND: Medullary thyroid carcinoma (MTC) is a relatively rare thyroid malignancy and its clinical course varies among patients due to its familial association. A number of prognostic factors have been studied, but the significance of these factors remains controversial. We evaluated the progression free survival (PFS) and overall survival (OS) of MTC and its association with tumour marker rising velocity and serum calcitonin (Ct) doubling time (DT). METHODS: Analysis of 83 (8.7%) consecutive MTC patients registered at a single centre between 1995 and 2015. The impact of tumour respectability, TNM stage, multiple endocrine neoplasia (MEN) syndrome, local recurrence, Ct DT and Ct rising velocity on PFS and OS was analysed. Median follow-up was 4.3 years (range: 1-18 years). RESULTS: Eighty-three (8.7%) of all thyroid cancers registered at our centre were MTC. Fifty-five males, 28 females. Mean age 39 years [range: 17-72 years]. Twenty-two were unresectable and 61 resectable. Five-year and 10-year OS was 84% and 77% respectively. Of 68 with follow up greater than a year; 20 (29.4%) were cured, 15 (22.1%) had biochemical evidence of disease, three (4.4%) had stable macroscopic disease and 30 (44.1%) had recurrent/progressive disease. Sixteen (23.5%) died. On multivariate analysis, T4 tumour, male gender, nodal and distant metastases, tumour resectibility, Ct DT less than two years and tumour marker rising velocity of greater than 0.05pg/ml/month were poor prognostic factors (pvalue <0.05). Age and association with MEN syndrome had no statistically significant survival impact. Radiotherapy reduced local relapse in patients with nodal disease. Total thyroidectomy with nodal clearance lessened relapses. CONCLUSION: Clinical stage and pathological aspects are predictors of disease progression. Persistent biochemical evidence of MTC does not affect OS, however, Ct DT < 2 years and rapid rate of tumour marker rise predict disease progression.

Laparoscopic adrenalectomy as an effective approach to massive bilateral pheochromocytomas.

Pheochromocytomas are catecholamine-secreting neoplasms, arising from adrenomedullary chromaffin cells. In type 2 multiple endocrine neoplasia (MEN2) syndrome, pheochromocytomas are usually benign but with predisposition to be bilateral (50%-80% of cases).The authors present the case of a young patient diagnosed with uncommonly large bilateral cystic pheochromocytomas and simultaneous detection of medullary thyroid carcinoma. Molecular testing confirmed germline RET codon C634 mutation, consistent with MEN2A syndrome. The patient underwent bilateral laparoscopic adrenalectomy plus total thyroidectomy with central lymph node dissection without associated complications. The histopathological study of the surgical specimens revealed bilateral benign pheochromocytomas (Ki67 of 2%) and a medullary carcinoma of the thyroid T1bN0M0; R0, respectively. One year after surgery, the patient was considered free of disease.This case demonstrates that bilateral laparoscopic adrenalectomy can be a safe and feasible approach for phechromocytomas in MEN2 syndrome, even in lesions with large diameter. However, due to elevated possibility of recurrence, patients should maintain lifelong follow-up.