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

Familial isolated primary hyperparathyroidism (FIHP) is an autosomal dominant disorder that is characterized by an early stage of either multiple endocrine neoplasia type 1 (MEN1) or hyperparathyroidism-jaw tumor (HPT-JT) syndrome. We report here on a case of a 42-years old woman who was diagnosed with papillary thyroid cancer and primary hyperparathyroidism. Her younger brother also had primary hyperparathyroidism. On the genetic analysis, they were both proven to have a novel frameshift mutation in the MEN1 gene (exon 10).
Female ; Frameshift Mutation ; Humans ; Hyperparathyroidism, Primary ; Multiple Endocrine Neoplasia Type 1 ; Siblings ; 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

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.
Adenoma ; Adrenalectomy ; Adrenocortical Adenoma ; Carcinoid Tumor ; Female ; Humans ; Hyperparathyroidism ; Hyperparathyroidism, Primary ; Hyperplasia ; Lipoma ; Mass Screening ; Middle Aged ; Multiple Endocrine Neoplasia ; Multiple Endocrine Neoplasia Type 1 ; Parathyroidectomy ; Pituitary Neoplasms ; Pylorus

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

About 20%–30% of all cases of multiple endocrine neoplasia type 2A (MEN 2A) is accompanied by primary hyperparathyroidism. These patients undergo parathyroidectomy and, if needed, autotransplantation. In rare cases, autotransplanted parathyroid tissues can cause hypoparathyroidism due to failure of transplantation or hyperparathyroidism due to proliferation of the transplanted tissue. A 68-year-old female with MEN 2A underwent left adrenalectomy for pheochromocytoma 15 years prior to presentation and total thyroidectomy, central and right lateral neck lymph node dissection, and subtotal parathyroidectomy with autotransplantation for medullary thyroid cancer and primary hyperparathyroidism 6 years previous. Recently, a doubtful parathyroid adenoma was detected in the left sternocleidomastoid muscle on ultrasonography and on an additional sestamibi scan. The mass was excised and histologically confirmed as parathyroid adenoma. This is a very rare case, and it suggests that long-term regular monitoring of serum calcium and intact parathyroid hormone levels is necessary after parathyroid autotransplantation.
Adrenalectomy ; Aged ; Autografts ; Calcium ; Female ; Humans ; Hyperparathyroidism* ; Hyperparathyroidism, Primary ; Hypoparathyroidism ; Lymph Node Excision ; Multiple Endocrine Neoplasia Type 2a* ; Multiple Endocrine Neoplasia* ; Neck ; Parathyroid Glands ; Parathyroid Hormone ; Parathyroid Neoplasms ; Parathyroidectomy ; Pheochromocytoma ; Recurrence ; Thyroid Neoplasms ; Thyroidectomy ; Transplantation, Autologous ; Ultrasonography

About 20%–30% of all cases of multiple endocrine neoplasia type 2A (MEN 2A) is accompanied by primary hyperparathyroidism. These patients undergo parathyroidectomy and, if needed, autotransplantation. In rare cases, autotransplanted parathyroid tissues can cause hypoparathyroidism due to failure of transplantation or hyperparathyroidism due to proliferation of the transplanted tissue. A 68-year-old female with MEN 2A underwent left adrenalectomy for pheochromocytoma 15 years prior to presentation and total thyroidectomy, central and right lateral neck lymph node dissection, and subtotal parathyroidectomy with autotransplantation for medullary thyroid cancer and primary hyperparathyroidism 6 years previous. Recently, a doubtful parathyroid adenoma was detected in the left sternocleidomastoid muscle on ultrasonography and on an additional sestamibi scan. The mass was excised and histologically confirmed as parathyroid adenoma. This is a very rare case, and it suggests that long-term regular monitoring of serum calcium and intact parathyroid hormone levels is necessary after parathyroid autotransplantation.
Adrenalectomy ; Aged ; Autografts ; Calcium ; Female ; Humans ; Hyperparathyroidism* ; Hyperparathyroidism, Primary ; Hypoparathyroidism ; Lymph Node Excision ; Multiple Endocrine Neoplasia Type 2a* ; Multiple Endocrine Neoplasia* ; Neck ; Parathyroid Glands ; Parathyroid Hormone ; Parathyroid Neoplasms ; Parathyroidectomy ; Pheochromocytoma ; Recurrence ; Thyroid Neoplasms ; Thyroidectomy ; Transplantation, Autologous ; Ultrasonography

Parathyroid carcinoma is a rare cause of primary hyperparathyroidism and commonly metastasize to lymph node, lung, liver, and bone. In Korea, there has been no report of distant metastasis in parathyroid carcinoma except for one case of pulmonary metastasis. A 58-year-old man presenting with weakness, nausea, and a palpable thyroid nodule visited our hospital. Elevated serum calcium and parathyroid hormone (PTH) concentration allowed the diagnosis of hyperparathyroidism. Two discrete masses were identified by neck ultrasound scan, computed tomography (CI') and Tc-Sestamibi scan in the left lobe of thyroid gland and ipsilateral parathyroid gland. So multiple endocrine neoplasia (MEN) type 2A" was suspected initially, but postoperative histological diagnosis was left parathyroid carcinoma with solitary nodular lesion invading left thyroid gland. He was successfully treated with left parathyroidectomy and left thyroid lobectomy.
Calcium ; Diagnosis ; Humans ; Hyperparathyroidism ; Hyperparathyroidism, Primary ; Korea ; Liver ; Lung ; Lymph Nodes ; Middle Aged ; Multiple Endocrine Neoplasia ; Multiple Endocrine Neoplasia Type 2a ; Nausea ; Neck ; Neoplasm Metastasis ; Parathyroid Glands ; Parathyroid Hormone ; Parathyroid Neoplasms* ; Parathyroidectomy ; Thyroid Gland* ; Thyroid Nodule ; Ultrasonography