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

This is the first report of papillary thyroid carcinoma combined with multiple endocrine neoplasia type 1 (MEN1) in Korea. MEN1 is a hereditary disease comprising neoplastic disorders such as pituitary, parathyroid and pancreatic neuroendocrine tumor, such as gastrinoma. But papillary thyroid cancer was never regarded as its component before in Korea. Herein we present a 39-year-old woman who manifested typical features of MEN1 with a coincidental papillary thyroid carcinoma. Although the family history of MEN1 was definite, her genetic analysis of DNA had revealed no germline mutation in MEN1 gene locus. Unidentified culprit gene unable us further genetic study to find LOH (loss of heterogeneity) in 11q13, the possible explanation of papillary thyroid carcinoma as a new component of MEN1. As we have first experienced a case of MEN1 combined with papillary thyroid carcinoma in Korea, we report it with the review of literature.
Adult ; Carcinoma, Papillary/genetics/*pathology ; Diagnosis, Differential ; Female ; Humans ; Multiple Endocrine Neoplasia Type 1/genetics/*pathology ; Mutation ; Proto-Oncogene Proteins/genetics ; Thyroid Neoplasms/genetics/*pathology

Multiple endocrine neoplasia (MEN) mutation is an autosomal dominant disorder characterized by the occurrence of parathyroid, pancreatic islet, and anterior pituitary tumors. The incidence of insulinoma in MEN is relatively uncommon, and there have been a few cases of MEN manifested with insulinoma as the first symptom in children. We experienced a 9-year-old girl having a familial MEN1 mutation. She complained of dizziness, occasional palpitation, weakness, hunger, sweating, and generalized tonic-clonic seizure that lasted for 5 minutes early in the morning. At first, she was only diagnosed with insulinoma by abdominal magnetic resonance images of a 1.3 × 1.5 cm mass in the pancreas and high insulin levels in blood of the hepatic vein, but after her father was diagnosed with MEN1. We found she had familial MEN1 mutation, and she recovered hyperinsulinemic hypoglycemia after enucleation of the mass. Therefore, the early genetic identification of MEN1 mutation is considerable for children with at least one manifestation.
Alleles ; Base Sequence ; Child ; DNA Mutational Analysis ; Female ; Humans ; Hypoglycemia/diagnosis ; Insulin/blood ; Insulinoma/diagnostic imaging/*pathology ; Magnetic Resonance Imaging ; Multiple Endocrine Neoplasia Type 1/*diagnosis/pathology ; Pancreatic Neoplasms/diagnostic imaging/*pathology ; Pedigree ; Polymorphism, Single Nucleotide ; Proto-Oncogene Proteins/genetics ; Seizures/complications

Zollinger-Ellison syndrome (ZES) is characterized by gastrinoma and resultant hypergastrinemia, which leads to recurrent peptic ulcers. Because gastrinoma is the most common pancreatic endocrine tumor seen in multiple endocrine neoplasia type I (MEN 1), the possibility of gastrinoma should be investigated carefully when patients exhibit symptoms associated with hormonal changes. Ureteral stones associated with hyperparathyroidism in the early course of MEN 1 are known to be its most common clinical manifestation; appropriate evaluation and close follow-up of patients with hypercalcemic urolithiasis can lead to an early diagnosis of gastrinoma. We report a patient with ZES associated with MEN 1, and urolithiasis as the presenting entity. A 51-year-old man visited the emergency department with recurrent epigastric pain. He had a history of calcium urinary stone 3 years ago, and 2 years later he had 2 operations for multiple jejunal ulcer perforations; these surgeries were 9 months apart. He was taking intermittent courses of antiulcer medication. Multiple peripancreatic nodular masses, a hepatic metastasis, parathyroid hyperplasia, and a pituitary microadenoma were confirmed by multimodal imaging studies. We diagnosed ZES with MEN 1 and performed sequential surgical excision of the gastrinomas and the parathyroid adenoma. The patient received octreotide injection therapy and close follow-up.
Gastrinoma/metabolism/pathology/ultrasonography ; Gastrins/metabolism ; Humans ; Immunohistochemistry ; Liver/radiography ; Magnetic Resonance Imaging ; Male ; Mesenteric Artery, Superior/radiography ; Middle Aged ; Multimodal Imaging ; Multiple Endocrine Neoplasia Type 1/complications/*diagnosis/radiography ; Pancreas/radiography/radionuclide imaging ; Pituitary Gland/radiography ; Positron-Emission Tomography ; Radiopharmaceuticals/diagnostic use ; Thyroid Gland/ultrasonography ; Tomography, X-Ray Computed ; Urolithiasis/*diagnosis/etiology ; Zollinger-Ellison Syndrome/complications/*diagnosis