비전형적인 임상경과를 보인 제1형 다발성 내분비선종 1예

최윤선,배연선,구본정,조영석,김영건,노흥규,송민호 대한내분비학회 2008 Endocrinology and metabolism Vol.23 No.4

Multiple endocrine neoplasia type 1 (MEN 1) is characterized by the combined occurrence of primary hyperparathyroidism, enteropancreatic tumors and anterior pituitary adenoma. Yet carcinoid tumors, adrenal adenoma and lipoma might exist simultaneously. Thymic carcinoid tumors, which are recognized as one of the causes of death for patients with MEN 1, are uncommon and their natural history has barely been investigated. A 51-year-old man, who had undergone surgery and radiation therapy for thymic carcinoid tumor 15 years ago, was admitted to our hospital due to hypercalcemia that was detected on a routine health checkup. We found that he had hyperparathyroidism, a nonfunctioning pancreatic tumor and thyroid papillary microcarcinoma. We had studied the genetic alteration of the MEN 1 gene (menin) by using leukocyte genomic DNA. This genetic analysis clearly showed the missense mutation of the MEN 1 gene (V215M on exon 3). The thymic carcinoid tumor in this patient showed a relatively indolent course, in contrast to that for the ordinary MEN 1 patient, and this patient's thyroid papillary microcarcinoma was discovered incidentally. We present here this atypical case along with a review of the relevant literature. Multiple endocrine neoplasia type 1 (MEN 1) is characterized by the combined occurrence of primary hyperparathyroidism, enteropancreatic tumors and anterior pituitary adenoma. Yet carcinoid tumors, adrenal adenoma and lipoma might exist simultaneously. Thymic carcinoid tumors, which are recognized as one of the causes of death for patients with MEN 1, are uncommon and their natural history has barely been investigated. A 51-year-old man, who had undergone surgery and radiation therapy for thymic carcinoid tumor 15 years ago, was admitted to our hospital due to hypercalcemia that was detected on a routine health checkup. We found that he had hyperparathyroidism, a nonfunctioning pancreatic tumor and thyroid papillary microcarcinoma. We had studied the genetic alteration of the MEN 1 gene (menin) by using leukocyte genomic DNA. This genetic analysis clearly showed the missense mutation of the MEN 1 gene (V215M on exon 3). The thymic carcinoid tumor in this patient showed a relatively indolent course, in contrast to that for the ordinary MEN 1 patient, and this patient's thyroid papillary microcarcinoma was discovered incidentally. We present here this atypical case along with a review of the relevant literature.

Multiple Endocrine Neoplasia Type 1 with Multiple Leiomyomas Linked to a Novel Mutation in the MEN1 Gene

최희경,김세현,문재훈,이윤희,강은석,안철우,차봉수,이은직,김경래,이현철,정선용,김현주,임승길,이유미 연세대학교의과대학 2008 Yonsei medical journal Vol.49 No.4

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominantly inherited syndrome. MEN1 is characterized by the presence of functioning and nonfunctioning tumors or hyperplasia of the pituitary gland, parathyroid glands, and pancreatic islet cells. In addition, MEN1 carriers can have adrenal or thyroid tumors and non-endocrine tumors, such as lipomas, angiofibromas, and leiomyomas. Although leiomyoma is not a major component of MEN1, it is thought to occur more frequently than expected. However, there has been no report of a case of MEN1 with leiomyoma in Korea so far. This report describes a patient with multiple leiomyomas in MEN1. A 50-year-old woman was referred for further evaluation of elevated calcium levels and osteoporosis. Biochemical abnormalities included hypercalcemia with elevated parathyroid hormone. There was hyperprolactinemia with pituitary microadenoma in sella MRI. An abdominal MRI demonstrated adrenal nodules and leiomyomas in the bladder and uterus. Endoscopic ultrasonography demonstrated esophageal leiomyoma and pancreatic islet cell tumor. A subtotal parathyroidectomy with thymectomy was performed. Sequencing of the MEN1 gene in this patient revealed a novel missense mutation (D350V, exon 7). This is the first case of MEN1 accompanied with multiple leiomyomas, parathyroid adenoma, pituitary adenoma, pancreatic tumor, and adrenal tumor.

새로운 MEN1 유전자 돌연변이가 증명된 가족성 제1형 다발내분비종양 1예

김민정,김은희,신미선,김주희,나희경,박성준,이상아,고은희,이우제,송기호,박중열,이기업,김구환,유한욱,김민선 대한내분비학회 2011 Endocrinology and metabolism Vol.26 No.2

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder characterized by the occurrence of multiple tumors in the parathyroid gland, pancreatic islet, and pituitary gland. This condition is caused by mutations of MEN1, a tumor suppressor gene. Thus far, 565 different germline and somatic mutations of the MEN1 gene have been reported. Herein, we describe the case of a 23-year-old woman who suffered from a repetitive loss of consciousness. After workup, the patient was diagnosed with MEN1 with insulinoma, hyperparathyrodism due to parathyroid adenoma, and non-functioning pituitary microadenoma. She underwent a partial parathyroidectomy and distal pancreatectomy. Familial screening of MEN1 revealed that her brother had prolactinoma,hyperparathyroidism, pancreatic gastrinoma and non-functioning adrenal adenoma. Her father had hyperparathyroidism,pancreatic tumor, and adrenal adenoma. Upon genetic analysis of the MEN1 gene, a novel mutation in the MEN1 gene (exon 1,c.251del; p.Ser84LuefsX35) was detected in the patient, as well as her father and brother.

Multiple endocrine neoplasia type 1 with anterior mediastinal parathyroid adenoma

Hye Lim Park,Ie Ryung Yoo,Sung Hoon Kim,Sohee Lee 대한외과학회 2016 Annals of Surgical Treatment and Research(ASRT) Vol.91 No.6

The most common manifestation of multiple endocrine neoplasia type 1 (MEN1) is hyperparathyroidism. Treatment of hyperparathyroidism in MEN patients is surgical removal of the parathyroid glands, however ectopic parathyroid gland is challenging for treatment. A 51-year-old female, the eldest of 3 MEN1 sisters, had hyperparathyroidism with ectopic parathyroid adenoma in the mediastinal para-aortic region, which was detected by technetium-99m (Tc-99m) sestamibi scintigraphy and single-photon emission computed tomography/computed tomography (SPECT/CT). She underwent total parathyroidectomy with video-assisted thoracoscopic surgery on an anterior mediastinal mass. Anterior mediastinal parathyroid adenoma in MEN1 patients is rare. Precise localization of an ectopic parathyroid gland with Tc-99m sestamibi SPECT/CT can lead to successful treatment of hyperparathyroidism. This is the first reported case in the literature of mediastinal parathyroid adenoma in MEN1 patient visualized by Tc-99m sestamibi SPECT/CT.

침습성 거대프로락틴분비종양으로 발현된 다발내분비샘종양1형 1예

차진훈 ( Jinhoon Cha ),김진서 ( Jin Seo Kim ),한정석 ( Jung Suk Han ),박연원 ( Yeon Won Park ),김민주 ( Min Joo Kim ),구윤희 ( Yun Hyi Ku ),김홍일 ( Hong Il Kim ) 대한내과학회 2016 대한내과학회지 Vol.91 No.3

Pituitary tumors occur in 15-50% of patients with multiple endocrine neoplasia of type 1 (MEN1). To the best of our knowledge, no MEN1 case in which the initial lesion was an invasive giant prolactinoma has been reported from Korea. We describe a patient in whom a skull-base tumor involved the sellar and parasellar spaces. A 49 year-old female presented with headache and diplopia. The tumor was ultimately identified as a giant prolactinoma; the serum prolactin concentration increased from 155.6 ng/mL to 3,234.3 ng/mL after cranial irradiation. She was evaluated in terms of incidental hypercalcemia and was found to have parathyroid hyperplasia. Genetic analysis revealed a missense mutation in the MEN1 gene (c.643G>A, p.Val215Met). Two years of treatment with a dopamine agonist reduced, but did not normalize, the serum prolactin concentration. We highlight the aggressive behavior of the giant skull-base tumor, and the diagnostic delay caused by a high-dose hook effect of the MEN1-related prolactinoma. (Korean J Med 2016;91:300-305)

Characteristics of the Germline MEN1 Mutations in Korea: A Literature Review

이성철,민준원,김유미,장명철 대한갑상선-내분비외과학회 2014 The Koreran journal of Endocrine Surgery Vol.14 No.1

Purpose: Multiple endocrine neoplasia type 1 (MEN-1) is an autosomal dominant disease caused by the MEN1 germline mutation. We reviewed previous reports in order to sum-marize the characteristics of germline MEN1 mutation in Korea.Methods: We retrieved the relevant literature regarding MEN1 germline mutation in Korea using the Pubmed (http://www.pubmed.org/) and Koreamed (http://www.koreamed.org/) databases from 2000 to 2012. We evaluated the pedigree of the patients in order to exclude the same, repeated families. We collected all data on the types of mutations and clinical characteristics.Results: There were nine studies with 12 cases of MEN1 mutations in Korea. Two cases were sporadic MEN-1. C.196_200dupAGCCC was reported in three families. There were six cases of frameshift mutation, three cases of missense mutation, two cases of nonsense mutation, and one case of splice site mutation. Five mutations were novel mutations not previously reported.Conclusion: We summarized the characteristics of germline MEN1 mutations in Korea. Genetic testing of MEN1 is rare in Korea; however, it will be useful in preclinical diagnosis and genetic counseling.

정기 건강 검진상 우연히 발견된 무증상의 제1형 다발성 내분비선종증 1예

조평산,박훈,이국행,이명철 대한이비인후과학회 2012 대한이비인후과학회지 두경부외과학 Vol.55 No.6

Multiple endocrine neoplasia type 1 (MEN 1) is characterized by the coexistence of primary hyperparathyroidism, enteropancreatic tumors, and anterior pituitary adenoma. Also adrenal adenoma, lipoma, carcinoid tumors could exist simultaneously on the atypical clinical course of MEN 1. Among these diseases, primary hyperparathyroidism is the most common manisfestation of MEN 1 syndrome. However, it sometimes presents no clinical symptoms and is incidentally detected on medical checkup. A 48-year-old woman, while undergoing a regular medical check-up, was diagnosed with primary hyperparathyroidism. Further studies showed concurrence of pancreatic tumor and adrenal tumor, but there was no pituitary lesion. The patient underwent parathyroidectomy with auto-implantation of parathyroid tissue, pylorus preserving pancreatico-duodenectomy and partial adrenalectomy. The pathological test confirmed it to be parathyroid hyperplasia, well-differentiated pancreatic endocrine carcinoma and adrenal cortical adenoma. We report this atypical and asymptomatic case of MEN 1 with a review of the relevant literature.

Genetic and Epigenetic Analysis in Korean Patients with Multiple Endocrine Neoplasia Type 1

Yoon Jung Chung,황세나,정종주,Sun Yong Song,김세훈,이유미 대한내분비학회 2014 Endocrinology and metabolism Vol.29 No.3

Background: Multiple endocrine neoplasia type 1 (MEN1) is a familial syndrome characterized by the parathyroid, pancreas and pituitary tumors. Parathyroid tumors are the most common clinical manifestations, occurring in more than 90% of MEN1 patients. Heterozygous germline mutations of the MENIN gene underlie the tumorigenesis in MEN1 and epigenetic alterations along with germline mutations may contribute to tumorigenesis. Here, we investigated the associations between genotype and phenotype in Korean MEN1 patients. Methods: We analyzed medical records from 14 unrelated MEN1 patients who had newly confirmed MENIN germline mutations, together with 14 previous reports in Korea. Aberrant DNA methylations were also examined in MEN1-related parathyroid tumors using the Infinium HumanMethylation 450 BeadChip. Results: Total 28 germline mutations of MENIN were relatively highly concentrated in exons 7 and 8 compared to previous reports from Western countries. Six mutations (c.111dupT/p.S38Ffs*79, c.225_226insT/p.T76Yfs*41, c.383_398del16/p.S128Tfs*52, c.746dupT/p.H250Afs*20, c.1150G>T/p.E384*, and c.1508G>A/p.G503N) were newly found in the present study. Of interest, four patients (15%) showed unusual initial presentations and three patients were diagnosed incidentally at the general medical checkup. We also found three distinct sites in exon 2 of MENIN were significantly hypomethylated in the MEN1 parathyroid tumors, comparing correspondent blood samples. Conclusion: We also have found a lack of genotype/phenotype correlation in Korean MEN1 patients. There were not a few unusual initial manifestations in MEN1 patients, thus, genetic testing for the MENIN germline mutations can provide important information for the better prognosis. Further studies are warranted to investigate altered DNA methylations in the MENIN gene involved in tumorigenesis.

Genetic Analysis of Multiple Endocrine Neoplasia Type 1 (MEN1) Leads to Misdiagnosis of an Extremely Rare Presentation of Intrasellar Cavernous Hemangioma as MEN1

이동민,유승희,윤현화,이강록,엄영실,이기영,김병준,김연순,박레병,김광원,이시훈 대한내분비학회 2014 Endocrinology and metabolism Vol.29 No.2

Background: Multiple endocrine neoplasia type 1 (MEN1) is a rare inherited disorder characterized by the simultaneous occurrence of endocrine tumors in target tissues (mainly the pituitary, endocrine pancreas, and parathyroid glands). MEN1 is caused by mutations in the MEN1 gene, which functions as a tumor suppressor and consists of one untranslated exon and nine exons encoding the menin protein. This condition is usually suspected when we encounter patients diagnosed with tumors in multiple endocrine organs, as mentioned above. Methods: A 65-year-old woman who underwent surgery for a pancreatic tumor (serous cystadenoma) 5 years previously was referred to our hospital due to neurologic symptoms of diplopia and left ptosis. Brain magnetic resonance imaging revealed a 3.4-cm lesion originating from the cavernous sinus wall and extending into the sellar region. It was thought to be a nonfunctioning tumor from the results of the combined pituitary function test. Incidentally, we found that she also had a pancreatic tumor, indicating the necessity of genetic analysis for MEN1. Results: Genomic analysis using peripheral leukocytes revealed a heterozygous c.1621G>A mutation in the MEN1 gene that was previously reported to be either a pathogenic mutation or a simple polymorphism. We pursued a stereotactic approach to the pituitary lesion, and microscopic findings of the tumor revealed it to be an intrasellar cavernous hemangioma, a rare finding in the sellar region and even rarer in relation to oculomotor palsy. The patient recovered well from surgery, but refused further evaluation for the pancreatic lesion. Conclusion: There is great emphasis placed on genetic testing in the diagnosis of MEN1, but herein we report a case where it did not assist in diagnosis, hence, further discussion on the role of genetic testing in this disease is needed. Also, in cases of pituitary tumor with cranial nerve palsy, despite its low prevalence, intrasellar cavernous hemangioma could be suspected.

Review : The Current Strategy for Managing Pancreatic Neuroendocrine Tumors in Multiple Endocrine Neoplasia Type 1

( Yusuke Niina ),( Nao Fujimori ),( Taichi Nakamura ),( Hisato Igarashi ),( Takamasa Oono ),( Kazuhiko Nakamura ),( Masaki Kato ),( Robert T. Jensen ),( Tetsuhide Ito ),( Ryoichi Takayanagi ) The Editorial Office of Gut and Liver 2012 Gut and Liver Vol.6 No.3

Multiple endocrine neoplasia type 1 (MEN1) is an inherited autosomal dominant disease presenting with pancreatic neuroendocrine tumors (pNETs), parathyroid tumors, or pitu-itary tumors. Using the PubMed database, we reviewed the literature on information regarding the proper diagnosis and treatment of MEN1-associated pNET. Many cases of MEN1-associated pNET are functioning pNETs. Gastrinomas and insulinomas tend to occur frequently in the duodenum and pancreas, respectively. In addition to diagnostic imaging, the selective arterial secretagogue injection test (SASI test) is useful for localizing functioning pNET. The standard treat-ment is surgical resection. However, in the case of a func-tioning pNET, the tumor should first be accurately located using the SASI test before an appropriate surgical method is selected. In cases of a MEN1-associated non-functioning pNET that exceeds 2 cm in diameter, the incidence of distant metastasis is significantly increased, and surgery is recom-mended. In cases of unresectable pNET, a somatostatin analog has been shown to demonstrate antitumor effects and is considered to be a promising treatment. In addition, molecular-targeted drugs have recently been found to be ef-fective in phase III clinical trials. (Gut Liver 2012;6:287-294)