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

A 9-year-old boy presented with increased sweating and abdominal pain. His mother and uncle had been diagnosed with bilateral pheochromocytoma and medullary thyroid carcinoma. Magnetic resonance imaging of the boy's abdomen revealed a 7.5 cm×7.0 cm×6.0 cm mass with a thick peripheral enhancing wall and fluid-fluid level at the right suprarenal region. His ¹²³I-meta-iodobenzylguanidine (MIBG) scan showed a large mass with increased MIBG uptake in the right adrenal gland. The levels of serum norepinephrine, urine epinephrine/norepinephrine, metanephrine, and vanillylmandelic acid were elevated. He, his mother, and two sisters tested positive for the known mutation of multiple endocrine neoplasia type 2A, Cys634Tyr in RET proto-oncogene. Laparoscopic tumor excision and right adrenalectomy were performed. Final diagnosis was pheochromocytoma with malignant behavior, based on adrenal gland scoring scale. However, there was no overt metastasis. After surgery, his symptoms resolved and abnormal laboratory tests were normalized.
3-Iodobenzylguanidine ; Abdomen ; Abdominal Pain ; Adrenal Glands ; Adrenalectomy ; Child ; Diagnosis ; Humans ; Magnetic Resonance Imaging ; Male ; Metanephrine ; Mothers ; Multiple Endocrine Neoplasia Type 2a ; Multiple Endocrine Neoplasia ; Neoplasm Metastasis ; Norepinephrine ; Pheochromocytoma ; Proto-Oncogenes ; Siblings ; Sweat ; Sweating ; Thyroid Neoplasms ; Vanilmandelic Acid

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: 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*

BACKGROUND AND OBJECTIVES: Multiple Endocrine Neoplasia type 2A (MEN 2A) is a syndrome that encompasses medullary thyroid carcinoma, pheochromocytoma, and hyperparathyroidism. Since MEN 2A is inherited as autosomal dominant, early detection and treatment is crucial. A genetic analysis of RET proto-oncogene of the family members of an index patient diagnosed as MEN 2A is reported. SUBJECTS AND METHOD: A patient diagnosed as MEN 2A and his 13 family members across two generations were studied. Initially, DNA was extracted from the peripheral blood leukocyte of family members and PCR amplification of exons 10, 11, 13, 14, 15, and 16 was performed, followed by investigation of point mutation on the RET proto-oncogene using a DNA sequence analyzer. Cervical ultrasonography was carried out in the 3 nephews who were revealed to have RET proto-oncogene point mutation. RESULTS: Point mutations of TGC (cys) to TGG (Trp) at codon 634 of exon 11 at RET proto-oncogene was detected by using automatic DNA sequence analyzing method in the index patient. The same point mutation was identified in 7 of the 13 family members. Cervical ultrasonography revealed bilateral thyroid nodules in all 3 nephews who had point mutations of RET proto-oncogene. CONCLUSION: With the genetic analysis of RET proto-oncogene, limitations of the conventional calcitonin stimulation test may be overcome, and a more complete approach can be achieved through early diagnosis by carrying out this screening test for point mutations in family members of the patient with MEN 2A.
Base Sequence ; Calcitonin ; Codon ; DNA ; Early Diagnosis ; Exons ; Family Characteristics ; Humans ; Hyperparathyroidism ; Leukocytes ; Mass Screening ; Multiple Endocrine Neoplasia Type 2a* ; Multiple Endocrine Neoplasia* ; Pheochromocytoma ; Point Mutation* ; Polymerase Chain Reaction ; Proto-Oncogenes ; Thyroid Neoplasms ; Thyroid Nodule ; Ultrasonography

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

OBJECTIVETo study the clinical characteristics and treatment of multiple endocrine neoplasia (MEN) type 2.

METHODSThe clinical features, diagnosis and treatment of from 1980 to 2002 8 cases of multiple endocrine neoplasia type 2 from Peking Union Medical College Hospital were reviewed and analyzed in clinical features, diagnosis and treatment retrospectively.

RESULTSSeven cases were with paroxysmal hypertension, the highest blood pressure was over 200 mm Hg (1 mm Hg = 0.133 kPa). Tumor was found in 3 cases. The diagnosis was confirmed by B-ultrasonography, CT and urine catecholamine test: six cases with MEN 2a 2 with MEN 2b. Six cases were medullary carcinoma of thyroid with or without parathyroidoma or hyperplasia, 1 with multiple mucosal neuromata. One case was pheochromocytoma with marfan's syndrome; 7 cases were with bilateral adrenal tumor. Total resection or resection ectomy was performed on different stages on adrenal gland, parathyroid tubercle. Average follow-up was 9 years. And the feedback was good.

CONCLUSIONThe diagnosis of multiple endocrine neoplasia type 2 depends on endocrine biochemical tests, B-ultrasonography and CT. When the pheochromocytoma and the other tumor exists at the same time, operation is the primary treatment, and it is better to remove the pheochromocytoma at the first.

Adolescent ; Adrenal Gland Neoplasms ; diagnosis ; surgery ; Adrenalectomy ; Adult ; Child ; Female ; Humans ; Male ; Middle Aged ; Multiple Endocrine Neoplasia Type 2a ; diagnosis ; surgery ; Parathyroid Neoplasms ; diagnosis ; surgery ; Parathyroidectomy ; Pheochromocytoma ; diagnosis ; surgery ; Retrospective Studies ; Thyroid Neoplasms ; diagnosis ; surgery ; Thyroidectomy

PURPOSE: The increased detection of hypercalcemia during health screening has been increased the diagnosis of hyperparathyroidism. The surgical treatment of primary hyperparathyroidism has been changing from standard exploration for all 4 parathyroid glands to minimally invasive surgery focused to abnormal gland. For the latter, exact preoperative localization is necessary. The aims of this study were to evaluate clinical features of patients with primary hyperparathyroidism and the preoperative localization methods. METHODS: A retrospective study was performed for 61 patients with primary hyperparathyroidism in Samsung Medical Center. RESULTS: There were 19 males and 42 females whose ages ranged from 12 to 76 years. Among 61 patients with primary hyperparathyroidism, there were 51 adenomas, 7 hyperplasias and 3 adenocarcinomas. Preoperative parathyroid hormone (PTH) level was increased in all patients except in a MEN IIA associated patient. Among the methods for preoperative localization, ultrasonography detected 47 of 55 cases (85.5%), (99m)Tc-sestamibi scan 40 of 49 cases (81.6%), MRI 3 of 5 cases (60.0%), CT 9 of 18 cases (50.0%) and Tl-Tc subtraction scan 6 of 9 cases (66.7%). In 26 patients who have been diagnosed as single nodular lesion in the same area by the parathyroid scan and ultrasonography, we could find a single parathyroid adenoma in that area during exploration. Postoperative PTH level of all patients but one were normalized. CONCLUSION: Single gland disease detected by both parathyroid scan and ultrasonography was mostly due to adenoma which can be treated safely by unilateral exploration or minimally invasive surgery.
Adenocarcinoma ; Adenoma ; Diagnosis ; Female ; Humans ; Hypercalcemia ; Hyperparathyroidism ; Hyperparathyroidism, Primary* ; Hyperplasia ; Magnetic Resonance Imaging ; Male ; Mass Screening ; Minimally Invasive Surgical Procedures ; Multiple Endocrine Neoplasia Type 2a ; Parathyroid Glands ; Parathyroid Hormone ; Parathyroid Neoplasms ; Retrospective Studies ; Ultrasonography

BACKGROUND AND OBJECTIVES: Hereditary medullary thyroid carcinoma is presented as a part of MEN2A (65-75%) or MEN2B, but can also be inherited alone, which is called familial medullary thyroid carcinoma. The author sought to detect point mutations of the RET proto-oncogene using the molecular genetic method on the family line of the familial medullary thyroid carcinoma, which is identified by the family history of an index patient, and to investigate the presence of point mutation carriers among the family members. SUBJECTS AND METHOD: DNA was extracted from the peripheral blood leukocyte of 5 patients who were assumed to have sporadic medullary thyroid carcinoma and 1 patient who was an index of a family line assumed to contain hereditary medullary thyroid carcinoma according to the family history. The PCR amplification of exons, 10, 11, 13, 14, 15, 16 was then carried out, and we investigated point mutations of the RET proto-oncogene using a DNA sequence analyzer. After identifying point mutation of the familial medullary carcinoma with them, the same investigation was carried out with their family. RESULTS: We identified point mutation of TGC (Cys)->CGC (Arg) at codon 618 of the RET proto-oncogene exon 10, using the automatic DNA sequence analyzing method on the index patient and detected the same point mutation with 4 of the 9 family members. Among them, the index patient and her mother who had biochemical and clinical symptoms underwent a total thyroidectomy and neck dissection and are now being followed up ; operations are scheduled for two other members later on. CONCLUSION: With the genetic analysis of RET proto-oncogene, we expect to overcome the limitations of the calcitonin stimulation test and that more complete approach through early diagnosis would be possible by carrying out the screening test for point mutation in patients with the hereditary medullary thyroid carcinoma.
Base Sequence ; Calcitonin ; Carcinoma, Medullary ; Codon ; DNA ; Early Diagnosis ; Exons ; Humans ; Leukocytes ; Mass Screening ; Molecular Biology ; Mothers ; Multiple Endocrine Neoplasia Type 2a ; Multiple Endocrine Neoplasia Type 2b ; Neck Dissection ; Point Mutation* ; Polymerase Chain Reaction ; Proto-Oncogenes ; Thyroid Gland* ; Thyroid Neoplasms* ; Thyroidectomy