PURPOSE: Multiple Endocrine Neoplasia Type 2A (MEN 2A) is an autosomal dominant disease characterized by development of the medullary thyroid cancer, adrenal pheochromocytoma and parathyroid hyperplasia. Gennline mutations of RET gene, which cause a susceptibility to MEN 2A syndrome, have been reported in MEN 2A families. The identification of germline mutation in family members with hereditary tumor syndrome makes the presymptomatic diagnosis possible. However, there are only a few reports on the germline mutation of RET gene in Korean patients with MEN 2A. This study was performed to investigate the germline mutation of RET gene in a Korean MEN 2A family. MATERIALS AND METHODS: Blood samples were taken from family members of a MEN 2A family. Mutational status was investigated using single strand conformation polymorphism (SSCP) method, and following direct sequencing. Basal level of calcitonin was measured, and calcium provocation test was done when the result of basal level of calcitonin was equivocal. RESULTS: A missense type germline mutation of RET gene was identified at codon 634 (TGC->TGG) in eight patients from the family. All patients with the germline mutation of RET gene showed elevation of calcitonin level either in basal test or in calcitonin provocation test. CONCLUSION: We identified a germline mutation of RET gene in a family with MEN 2A, and it would make the accurate presymptomatic diagnosis possible.
Calcitonin ; Calcium ; Codon ; Diagnosis ; Germ-Line Mutation ; Humans ; Hyperplasia ; Multiple Endocrine Neoplasia Type 2a* ; Multiple Endocrine Neoplasia* ; Pheochromocytoma ; Thyroid Neoplasms

Diagnostic Errors ; Humans ; Male ; Multiple Endocrine Neoplasia Type 2a/diagnosis* ; Myocarditis/diagnosis*

We report a case of multiple endocrine neoplasia (MEN) type 2A and summarize the clinical characteristics, diagnosis and treatment of this condition. The diagnosis of MEN type 2A relies on a comprehensive evaluation of the findings of ultrasound, CT and laboratory examinations, and early diagnosis and treatment is critical to improving the prognosis. Genetic testing of RET is the gold standard for diagnosis of MEN type 2A and 2B. Surgical intervention currently remains the primary choice of treatments of this disease.
Genetic Testing ; Humans ; Multiple Endocrine Neoplasia Type 2a ; diagnosis ; therapy ; Prognosis

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

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

BACKGROUND: Medullary thyroid carcinomas (MTC) have been reported as hereditary in about 25 ~30% of cases. The identification of germline mutation in RET proto-oncogene is important in the diagnosis of hereditary MTC, and occurs in three forms: MEN 2A, MEN 2B and familial MTC (FMTC). To evaluate the prevalence of the relationship of RET proto-oncogene mutation and genotype-phenotype was studied in Korean patients with MTC. METHODS: Genomic DNA was obtained from 29 patients, with MTC, who underwent a total thyroidectomy, between 1997 and 2003, at the Samsung Medical Center. There were 7 male and 22 female patients, with an average age of 39, ranging from 20 to 60 years. Exon 10, 11, 13, 14 and 16 of the RET proto-oncogene were amplified, with specific primers, using PCR. A sequencing analysis was performed on the PCR product using an automatic sequencing analyzer. RESULTS: Nine of the 29 patients (31%) were identified as having RET mutations. The average age of these 9 patients was 33 years, ranging from 20 to 51, with a female to male ratio of 2. Five patients had MEN 2A and one had FMTC, with the other 3 thought to have non-hereditary (sporadic) MTC. The 4 patients with MEN 2A had RET mutations on codon 634 of exon 11 (2 patients, C634R; 2 patients, C634Y) and the other patient on codon 618 of exon 10 (C618R). One patient with FMTC had a mutation on codon 634 (C634W). Three patients with sporadic MTC had RET mutations on codon 634 (2 patients, C634Y; 1 patient, C634S). However, no genotype- phenotype relationship could be found, due to the limited number of patients. CONCLUSION: Thirty-one percent (9/29) of the patients with MTC had RET proto-oncogene mutations. Three-quarters (9/12) of the Korean patients with MEN 2A, including another 7 patients reported in 3 papers in Korea, had RET mutations on codon 634 of exon 11 (4 patients, C634R; 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). Although no relations could be found between the genotypes and phenotypes, extensive prospective studies will be required to verify this.
Codon ; Diagnosis ; DNA ; Exons ; Female ; Genotype ; Germ-Line Mutation ; Humans ; Korea ; Male ; Multiple Endocrine Neoplasia Type 2a ; Multiple Endocrine Neoplasia Type 2b ; Phenotype ; Polymerase Chain Reaction ; Prevalence ; Proto-Oncogenes* ; Thyroid Gland* ; Thyroid Neoplasms* ; Thyroidectomy

PURPOSE: Medullary thyroid carcinoma (MTC) is an uncommon thyroid tumor and the clinical course is variable. Many prognostic factors for MTC have been studied, but the significance of some of these factors remains controversial. This study aimed to evaluate the prognosis of recurrent disease in patients suffering with MTC. METHODS: Fifty three patients who were operated for MTC from 1987 to 2006 in Seoul National University Hospital (SNUH) was retrospectively analyzed. Their medical records were reviewed for the demographic data, the laboratory data and the clinical course, the treatment and the long-term outcome. The median duration of follow-up was 66.5 months. Forty-two patients who were operated on primarily in this hospital were analyzed for their recurrence free survival. RESULTS: The mean age atdiagnosis was 41.8 years. There were 28 femaleand 25 male patients. Eleven patients (22.9%) had multifocal disease. There were 32 sporadic MTC patients, 15 MEN2A patients, 3 familial medullary thyroid carcinoma (FMTC) patients and 1 MEN 2B patient. The 10- and 15-year overall survival rates were 91.9% and 76.5%, respectively; the 5- and 10-year recurrence-free survival rates were 70.6% and 45.5%, respectively. By univariate statistical analysis, the stage (stage I/II vs. III/IV, P=0.025), extrathyroidal extension (P=0.039), cervical lymph node metastasis (P=0.044), and the postoperative calcitonin level (≥25 pg/ml) (P=0.003) were the significant factors that influenced recurrence. CONCLUSION: The overall prognosis of MTC is favorable. The significantfactors for a poor prognosis were the presence of lymph node metastasis, TNM stage III and IV, positive extrathyroidal extension at the first diagnosis and a high postoperative calcitonin level.
Calcitonin ; Diagnosis ; Follow-Up Studies ; Humans ; Lymph Nodes ; Male ; Medical Records ; Multiple Endocrine Neoplasia Type 2a ; Multiple Endocrine Neoplasia Type 2b ; Neoplasm Metastasis ; Prognosis ; Recurrence* ; Retrospective Studies ; Seoul ; Survival Rate ; Thyroid Gland* ; Thyroid Neoplasms*

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

Multiple endocrine neoplasia (MEN) Ila is an inherited disease characterized by the development of medullary thyroid carcinoma, pheochromocytoma and hyperparathyroidism. It has been shown to be associated with germ-line mutatians in the RET proto-oncogene. Presymptomatic screening of medullary thyroid carcinoma in MEN IIa families enables the early diagnosis of this tumor with its significant morbidity, We describe a 19-year-old woman fmm a MEN IIa family who was founded by DNA analysis to be a gene carrier of MEN IIa and then was diagnosed, using a pentagastrin stimulation test, as having presymptomatie medullary thyroid carcinoma She underwent thyroidectomy and histologic examination confirmed medullary thyroid carcinoma. It is cancluded that direct genetic analysis for mutations in the RET proto-oncogene should be the diagnstlc test of choice for identifying family members at risk for MEN IIa and thyroidectomy on the basis of genetic analysis is a rational course of action.
DNA ; Early Diagnosis ; Female ; Genes, vif ; Humans ; Hyperparathyroidism ; Male ; Mass Screening* ; Multiple Endocrine Neoplasia ; Multiple Endocrine Neoplasia Type 2a* ; Pentagastrin ; Pheochromocytoma ; Proto-Oncogenes ; Thyroid Gland* ; Thyroid Neoplasms* ; Thyroidectomy ; Young Adult

Multiple endocrine neoplasia 2A (MEN 2A) is an autosomal dominantly inherited disease, composed of medullary thyroid carcinoma, pheochromocytoma and hyperparathyroidism. The activation of germ-line mutations in the RET proto-oncogene are responsible for MEN 2. The analysis of the RET mutations has replaced the measurement of the calcitonin level in the diagnosis of the MEN carrier state. Specific RET codon mutations correlate with the MEN 2 syndromic variant, the age at onset of the medullary thyroid carcinoma (MTC) and the aggressiveness of the MTC. Herein, our experience of a 47-year-old woman, who had a bilateral pheochromocytoma and MTC, and MEN 2A confirmed by the detection of an RET proto-oncogene mutation at axon 10 on codon 618, is reported. Her sister was found to have the same mutant gene. After a total thyroidectomy and bilateral adrenalectomy, the calcitonin and catecholamine levels were normalized, and the patient discharged without problems. This case is reported, with a review of the literature.
Adrenalectomy ; Axons ; Calcitonin ; Carrier State ; Codon ; Diagnosis ; Female ; Germ Cells* ; Germ-Line Mutation* ; Humans ; Hyperparathyroidism ; Male ; Middle Aged ; Multiple Endocrine Neoplasia Type 2a ; Multiple Endocrine Neoplasia* ; Pheochromocytoma ; Proto-Oncogenes ; Siblings ; Thyroid Neoplasms ; Thyroidectomy