Multiple endocrine neoplasia (MEN) is defined as a disorder with neoplasms in two or more different hormonal tissues in several members of a family. MEN1, or Wermer's syndrome, is inherited as an autosomal dominant trait. This syndrome is characterized by neoplasia of the parathyroid glands, enteropancreatic tumors, anterior pituitary adenomas, and other neuroendocrine tumors with variable penetrance. Inherited medullary thyroid carcinoma (MTC) consists of MEN2A, MEN2B, and familial medullary thyroid cancer (FMTC). The identification of hereditary MTC has been facilitated in recent years by direct analysis of germline RET proto-oncogene mutation.
Carcinoma, Medullary ; Humans ; Multiple Endocrine Neoplasia ; Multiple Endocrine Neoplasia Type 1 ; Multiple Endocrine Neoplasia Type 2a ; Multiple Endocrine Neoplasia Type 2b ; Neuroendocrine Tumors ; Parathyroid Glands ; Penetrance ; Pituitary Neoplasms ; Proto-Oncogenes ; Thyroid Gland ; Thyroid Neoplasms

PURPOSE: Multiple Endocrine Neoplasm (MEN) is a rare, complex and familial disease. There are MEN syndromes are inherited in an autosomal dominant fashion with high penetrance. The variations in the RET gene play an important role in the MEN syndromes. Recent advances in diagnosis, treatment and genetic study of patients with MEN in Korean are reviewed. METHODS: There were 79 cases and 20 families with MEN syndromes in Korea which based on my experiences and 27 published papers. According to subtypes, there were classified and analyzed. RESULTS: Mean age was 37.9±11.5 years old. Sex ratio was 1:2.6. There were 7 families and 23 cases with MEN type I in Korean. The clinical characteristics of MEN I in Korean are mostly not different from the previous reports except older age (mean=43.2 old-year) at diagnosis. The frequency of the MEN I germ-line mutation in Korean MEN I (80%) families was similar to those reported previously. There were 13 families and 52 cases with MEN type II A in Korean. Three-quarters (9/12) of the Korean patients with MEN IIa had RET mutations on codon 634 of exon 11 (4 patients, C634; 4 patients, C634Y; 1 patient, C634W), but a quarter (3/12) had mutations on codon 618 of exon 10 (2 patients, C618R; 1 patient, C618S). A small medullary carcinoma in a patient of MEN type II A family was detected by genetic mutation screening in SMC. MEN IIb was reported only 4 cases. A case showed a codon 918 mutation (M918T) at exon 16 of RET proto-oncogene. CONCLUSION: Multiple endocrine neoplasia is rare hereditary cancer syndromes expressing a variety of tumors. With understanding of the molecular and clinical pathology of MEN syndromes, genetic screening is now feasible, and treatments have become more individualized based on genetic information of Korean.
Carcinoma, Medullary ; Codon ; Diagnosis ; Exons ; Genetic Testing ; Germ-Line Mutation ; Humans ; Korea ; Male ; Mass Screening ; Multiple Endocrine Neoplasia Type 1 ; Multiple Endocrine Neoplasia Type 2a ; Multiple Endocrine Neoplasia Type 2b ; Multiple Endocrine Neoplasia* ; Neoplastic Syndromes, Hereditary ; Pathology, Clinical ; Penetrance ; Proto-Oncogenes ; Sex Ratio

PURPOSE: Multiple endocrine neoplasia (MEN) syndrome is an inherited, autosomal dominant disease that presents as a combination of several endocrine tumors. Early diagnosis of this syndrome is difficult, because of the nonspecific symptoms and signs. This study analyzed early manifestations and clinical characteristics in patients with MEN syndrome. METHODS: Medical records were retrospectively reviewed and telephone interviews were conducted with 35 patients diagnosed as MEN syndrome at Samsung Medical Center from December 1994 to December 2009. RESULTS: The 35 patients had been diagnosed as MEN1 (n=14), MEN2A (n=19) and MEN2B (n=2). The early manifestations of the 14 MEN1 patients were related with hyperparathyroidism (n=5), pituitary tumor (n=3), and pancreatic endocrine tumor (n=2). There were tumors of the parathyroid gland in all 14 patients, anterior pituitary in eight patients, and pancreatic islet cells in seven patients. Four cases were incidentally detected during the screening examination. Six cases harbored a MEN1 gene mutation. The twenty-one patients diagnosed with MEN2 comprised medullary thyroid cancer (n=20), adrenal pheochromocytoma (n=15), and hyperparathyroidism (n=4). The MTC-related symptoms in the 21 MEN2 patients included neck mass or discomfort in 12 patients and pheochromocytoma-related symptoms in seven patients. Two cases were detected through familial genetic screening test. The RET gene mutationwas detected in 19 cases. CONCLUSION: Early manifestations of MEN syndrome were very different between the types of MEN and the types of its presenting tumor. The early diagnosis and proper management of MEN requires awareness of the clinical characteristics of each expressed tumor and is influenced by genetic screening methods.
Early Diagnosis ; Genetic Testing ; Humans ; Hyperparathyroidism ; Interviews as Topic ; Islets of Langerhans ; Male ; Mass Screening ; Medical Records ; Multiple Endocrine Neoplasia Type 1 ; Multiple Endocrine Neoplasia Type 2a ; Multiple Endocrine Neoplasia Type 2b ; Multiple Endocrine Neoplasia* ; Neck ; Parathyroid Glands ; Pheochromocytoma ; Pituitary Neoplasms ; Retrospective Studies ; Thyroid Neoplasms

Ganglioneuromas of the gastrointestinal tract are rare, but have an established association with genetic disorders, such as the multiple endocrine neoplasia (MEN) syndrome (type 2b) and neurofibromatosis (type 1). However, solitary ganglioneuromas are not associated with an increased risk for MEN 2b, neurofibromatosis type 1, or any other systemic conditions. Ganglioneuromas of the gastrointestinal tract have been reported to predominantly involve the colon and rectum, and are thereby occasionally detected during colonoscopy or surgery. Although there are no characteristic symptoms of solitary ganglioneuromas, symptoms can be induced by solitary ganglioneuromas, such as abdominal pain, bleeding, or obstruction, depending on the location and size. Herein we report a case of a solitary ganglioneuroma of the ileum. A 34-year-old man sought evaluation at our hospital for anemia. The medical and family histories were benign and there was no history of genetic disorders. The evaluation for anemia revealed iron-deficiency anemia and CT enterography revealed a single mass in the ileum. Laparoscopic resection of the lesion was performed and the pathologic examination confirmed an ileal ganglioneuroma.
Abdominal Pain ; Adult ; Anemia ; Anemia, Iron-Deficiency ; Colon ; Colonoscopy ; Ganglioneuroma ; Gastrointestinal Tract ; Hemorrhage ; Humans ; Ileum ; Multiple Endocrine Neoplasia ; Multiple Endocrine Neoplasia Type 2b ; Neurofibromatoses ; Neurofibromatosis 1 ; Rectum

Ganglioneuromas of the gastrointestinal tract are rare, but have an established association with genetic disorders, such as the multiple endocrine neoplasia (MEN) syndrome (type 2b) and neurofibromatosis (type 1). However, solitary ganglioneuromas are not associated with an increased risk for MEN 2b, neurofibromatosis type 1, or any other systemic conditions. Ganglioneuromas of the gastrointestinal tract have been reported to predominantly involve the colon and rectum, and are thereby occasionally detected during colonoscopy or surgery. Although there are no characteristic symptoms of solitary ganglioneuromas, symptoms can be induced by solitary ganglioneuromas, such as abdominal pain, bleeding, or obstruction, depending on the location and size. Herein we report a case of a solitary ganglioneuroma of the ileum. A 34-year-old man sought evaluation at our hospital for anemia. The medical and family histories were benign and there was no history of genetic disorders. The evaluation for anemia revealed iron-deficiency anemia and CT enterography revealed a single mass in the ileum. Laparoscopic resection of the lesion was performed and the pathologic examination confirmed an ileal ganglioneuroma.
Abdominal Pain ; Adult ; Anemia ; Anemia, Iron-Deficiency ; Colon ; Colonoscopy ; Ganglioneuroma ; Gastrointestinal Tract ; Hemorrhage ; Humans ; Ileum ; Multiple Endocrine Neoplasia ; Multiple Endocrine Neoplasia Type 2b ; Neurofibromatoses ; Neurofibromatosis 1 ; Rectum

Medullary thyroid carcinoma (MTC) is a relatively rare malignant thyroid disease that accounts for approximately 1% to 5% of all thyroid carcinomas. MTC occurs as a sporadic disease and as an inherited disease with the multiple endocrine neoplasia type 2A (MEN2A), MEN2B, and familial non-MEN medullary carcinoma (FMTC). MEN2A is characterized by MTC, pheochromocytoma, and parathyroid adenoma. The mutation of RET proto-oncogene plays an important role in MEN2A syndromes. Recently the authors diagnosed MEN2A patient and screened his family with thyroid ultrasonogram and RET proto-oncogene analysis. A genetic analysis of the peripheral leukocyte showed a codon 618 mutation (Cys618Arg) at exon 10 of the RET proto-oncogene in a family presenting third generations from age 7 to age 56 years. We report this case of MEN2A with a review of the related literatures.
Carcinoma, Medullary ; Codon ; Exons ; Family Characteristics ; Humans ; Leukocytes ; Multiple Endocrine Neoplasia Type 2a* ; Multiple Endocrine Neoplasia Type 2b ; Multiple Endocrine Neoplasia* ; Parathyroid Neoplasms ; Pheochromocytoma ; Proto-Oncogenes* ; Thyroid Diseases ; Thyroid Gland ; Thyroid Neoplasms ; Ultrasonography

Multiple endocrine neoplasia-IIb (MEN-IIb) is a rare hereditary autosomal dominant syndrome caused by mutations in the RET proto-oncogene. It's characterized by medullary thyroid carcinoma (MTC), pheochromocytoma (PHEO), mucosal neuromas, and Marfanoid habitus. Because of the rarity of MEN-IIb and finiteness of clinical cognition, the majority of the patients suffer a delayed diagnosis. A MEN-IIb patient with the lingual mucosal neuromas since childhood was admitted in the Third Xiangya Hospital of Central South University in November, 2018. He had surgical history of mitral valve prolapse and spinal deformity. He was diagnosed with MTC and PHEO at the age of 22 and 28, respectively, and received surgical treatments. Sequencing of RET gene revealed a de novo heterozygous p.M918T mutation in the patient. Being aware of the unique clinical phenotype and screening of RET gene mutation may lead to the early diagnosis and better long-term outcome for MEN-IIb.
Adrenal Gland Neoplasms ; Child ; Genes ; Humans ; Male ; Multiple Endocrine Neoplasia ; Multiple Endocrine Neoplasia Type 2a/genetics* ; Multiple Endocrine Neoplasia Type 2b/genetics* ; Mutation ; Proto-Oncogene Proteins c-ret/genetics* ; Thyroid Neoplasms/genetics*

Humans ; Multiple Endocrine Neoplasia Type 2b

No abstract available.
Multiple Endocrine Neoplasia Type 2a* ; Multiple Endocrine Neoplasia*

No abstract available.
Multiple Endocrine Neoplasia Type 2a* ; Multiple Endocrine Neoplasia*