Endocrinology and Metabolism

Case Reports

A Family Presenting with Catastrophic Features due to Pheochromocytoma Associated with Multiple Endocrine Neoplasia 2A.: Yun Jung Lee, Suk Chon, Sang Ho Lee, Tae Won Lee, Chun Gyoo Ihm, Tae June Noh, Seungjoon Oh, Jeong Taek Woo, Sung Woon Kim, Jin Woo Kim, Young Seol Kim; Endocrinol Metab. 2010;25(2):135-141. Published online June 1, 2010; DOI: https://doi.org/10.3803/EnM.2010.25.2.135

1,976 View
21 Download

Abstract PDF: Multiple endocrine neoplasia 2A (MEN 2A) is an autosomal dominant disease that consists of medullary thyroid carcinoma (MTC), pheochromocytoma and parathyroid hyperplasia. The activation of germ-line mutations in the RET proto-oncogene are responsible for MEN 2A. We describe here a rare case of MEN 2A in a patient who presented with an acute catecholamine-induced cardiomyopathy with cardiogenic shock and acute renal failure. The patient was diagnosed with pheochromocytoma and MTC associated with MEN 2A, which was confirmed by the detection of a RET proto-oncogene mutation at exon 11 on codon 634 (Cys634Arg). During familial screening, the patient's younger sister was found to have a benign thyroid nodule. Re-evaluation of this thyroid nodule revealed MTC with the same gene mutation. We also provide a review of the relevant literature.

A Case of Sporadic Medullary Thyroid Cancer with RET G691S Polymorphism.: Min Kyu Kang, Jung Min Lee, Ji Hyun Kim, Min Young Lee, Ji Hyun Kim, Sung Dae Moon, Je Ho Han, Sang Ah Chang; J Korean Endocr Soc. 2009;24(4):293-297. Published online December 1, 2009; DOI: https://doi.org/10.3803/jkes.2009.24.4.293

2,141 View
27 Download

Abstract PDF: Sporadic medullary thyroid carcinoma (MTC) is the most common form of MTC and somatic RET proto-oncogene mutations account for approximately 25% of the patients with sporadic MTC. However, other pathogeneses of sporadic MTC are still unclear. Not only RET mutation, but also polymorphisms of RET may have an association with sporadic MTC. We herein describe the association of MTC and RET proto-oncogene polymorphism. A 51-year-old man was diagnosed with MTC, which was incidentally found on a thyroid sonogram. The patient underwent total thyroidectomy and genetic mutational analysis of the RET gene. Genetic testing detected a polymorphism in codon 691 (G691S) on exon 11 of the RET proto-oncogene. His son and daughter had the same polymorphism. We report on this case along with a review of the related literature on RET gene polymorphism of sporadic MTC.

A Family of Multiple Endocrine Neoplasia Type 2A with a C634R Mutation and a G691S Polymorphism in RET Proto-oncogene.: Seoung Wook Yun, Won Sang Yoo, Koo Hyun Hong, Bae Hwan Kim, Min Ho Kang, Young Kwang Choo, Hee Yoon Park, Do Hee Kim, Hyun Kyung Chung, Myung Chul Chang, Mi Seon Kwon, Hee Jin Kim; J Korean Endocr Soc. 2007;22(6):453-459. Published online December 1, 2007; DOI: https://doi.org/10.3803/jkes.2007.22.6.453

2,277 View
32 Download
2 Crossref

Abstract PDF

Multiple endocrine neoplasia type 2A (MEN2A) is an autosomal dominant syndrome characterized by the presence of a medullary thyroid carcinoma, pheochromocytoma and hyperparathyroidism. MEN2A arises due to germline missense mutations of the RET proto-oncogene. Specific RET mutations correlate with the onset of age and the aggressiveness of a medullary thyroid carcinoma. However, the clinical presentation varies even within families, where patients carry the same mutation. Recently, it has been reported that polymorphisms of RET may have a modifier effect on the presentation. We experienced a case of 42-year-old man, whose bilateral pheochromocytoma and medullary thyroid carcinoma were incidentally found. Genetic testing detected a mutation in codon 634 (C634R) and a polymorphism in codon 691 (G691S) of the RET proto-oncogene. His mother, younger brother and his only son had the same mutation and polymorphism. We report this case with a review of the literature about RET gene polymorphisms.

Citations

Citations to this article as recorded by

A Family Presenting with Catastrophic Features due to Pheochromocytoma Associated with Multiple Endocrine Neoplasia 2A
Yun Jung Lee, Suk Chon, Sang-Ho Lee, Tae-Won Lee, Chun-Gyoo Ihm, Tae June Noh, Seungjoon Oh, Jeong-Taek Woo, Sung-Woon Kim, Jin-Woo Kim, Young Seol Kim
Endocrinology and Metabolism.2010; 25(2): 135. CrossRef
A Case of Sporadic Medullary Thyroid Cancer with RET G691S Polymorphism
Min-Kyu Kang, Jung-Min Lee, Ji-Hyun Kim, Min-Young Lee, Ji Hyun Kim, Sung Dae Moon, Je-Ho Han, Sang-Ah Chang
Journal of Korean Endocrine Society.2009; 24(4): 293. CrossRef

A Case of Familial Medullary Thyroid Carcinoma with a E768D Mutation in RET Proto-Oncogene.: Yeon Kyeong Kim, Jin Woo Kim, Sang Mi Ahn, Kyoung Eun Song, Sun Hye Jung, Dae Jung Kim, Yoon Sok Chung, Kwan Woo Lee, Chul Ho Kim, Ji Hee Hong, Seon Yong Jeong, Hyon Ju Kim; J Korean Endocr Soc. 2005;20(4):375-380. Published online August 1, 2005; DOI: https://doi.org/10.3803/jkes.2005.20.4.375

2,356 View
26 Download
2 Crossref

Abstract PDF

A medullary thyroid carcinoma, a neoplasm of parafollicular C cell origin, occurs as a sporadic or hereditary disease. A hereditary medullary thyroid carcinoma is an autosomal dominantly inherited disease, which is composed of multiple endocrine neoplasia 2A and 2B, with a familial medullary thyroid carcinoma. Germline mutations of the RET gene are the underlying cause of the majority of hereditary medullary carcinomas. Here, the case of a 42 years-old man with a familial medullary thyroid carcinoma, confirmed by the detection of a RET proto-oncogene mutation at exon 13 on codon 768 from a GAG(Glu) to a GAT(Asp), is described. The patient underwent a total thyroidectomy and modified radical neck dissection. His sister was found to have the same mutant gene.

Citations

Citations to this article as recorded by

A Case of Medullary Thyroid Carcinoma with de novo V804M RET Germline Mutation
Young Sik Choi, Hye Jung Kwon, Bu Kyung Kim, Su Kyoung Kwon, Yo Han Park, Jeong Hoon Kim, Sang Bong Jung, Chang Hoon Lee, Seong Keun Lee, Shinya Uchino
Journal of Korean Medical Science.2013; 28(1): 156. CrossRef
A Family of Multiple Endocrine Neoplasia Type 2A with a C634R Mutation and a G691S Polymorphism in RET Proto-oncogene
Seoung Wook Yun, Won Sang Yoo, Koo Hyun Hong, Bae Hwan Kim, Min Ho Kang, Young Kwang Choo, Hee Yoon Park, Do Hee Kim, Hyun-Kyung Chung, Myung-Chul Chang, Mi Seon Kwon, Hee Jin Kim
Journal of Korean Endocrine Society.2007; 22(6): 453. CrossRef

Original Articles

A Case of Multiple Endocrine Neoplasia 2A with Germ Line Mutation of RET Gene.: Hee Young Kim, Ji Yeon Lee, Sung Bum Kim, Kye Won Lee, Ji A Seo, Jeong Heon Oh, Sin Gon Kim, Kyung Mook Choi, Sei Hyun Baik, Dong Seop Choi, Nan Hee Kim; J Korean Endocr Soc. 2003;18(5):481-488. Published online October 1, 2003

1,242 View
19 Download

Abstract PDF: 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.

Analysis of Ret Proto-oncogene Mutation in Korean Patients with Medullary Thyroid Carcinomas.: Hyung Hoon Kim, Hyun Jin Kim, Yun Jae Chung, Yong Ki Min, Myung Shik Lee, Moon Kyu Lee, Kwang Won Kim, Chang Seok Ki, Jong Won Kim, Jae Hoon Chung; J Korean Endocr Soc. 2003;18(4):360-370. Published online August 1, 2003

1,506 View
26 Download

Abstract PDF: 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.

Case Report

A Case of Multiple Endocrine Neoplasia Type 2B associated with a M918T Mutation in RET Proto-Oncogene.: Tae Yong Kim, Jae Kyung Hwang, Min Kyong Moon, Young Joo Park, Do Joon Park, Seong Yeon Kim, Hong Kyu Lee, Yo Kyu Yoon, Bo Youn Cho; J Korean Endocr Soc. 2003;18(1):85-93. Published online February 1, 2003

1,272 View
17 Download

Abstract PDF: A multiple endocrine neoplasia type 2B(MEN2B) is the most distinct and aggressive form of the MEN type 2 variants. We report a case of a 24-years-old woman with MEN2B. The patient had previously undergone a Duhamel's operation due to a megacolon at 6 years old, minor surgery to remove small tumors on the lip at 8 years old, and a bilateral osteotomy of the femur, due to coxa valga, at 15 years old. She underwent a total thyroidectomy and neck dissection, due to a growing thyroid nodule, despite thyroxine treatment, at 19 years old. The pathology revealed a medullary thyroid carcinoma. There was no history of MEN 2B in her family. She had prominent lips, multiple oral mucosal masses, and marfanoid habitus. During the subsequent follow-up, a positron emission tomogram was taken due to a persistently high level of serum calcitonin, despite repeated neck dissections, which revealed a mass in the right adrenal gland. Adrenomedullary function tests showed high levels of urinary catecholamine metabolites, and a genetic analysis of the peripheral leukocyte showed a codon 918 mutation (Met918Thr) at exon 16 of the RET proto-oncogene. The patient underwent a right adrenalectomy and the pathology revealed a pheoch-romocytoma.

Original Article

Early Detection of Medullary Thyroid Cancer by Screening of the RET Proto-oncogene Germ Line Point Mutation in Family Members Affected with Hereditary Medullary Thyroid Cancer .: Sun Wook Kim, Tae Yong Kim, Young Joo Park, Won Bae Kim, Chan Soo Shin, Do Joon Park, Kyoung Soo Park, Seong Yeon Kim, Bo Youn Cho, Hong Kyu Lee; J Korean Endocr Soc. 2001;16(1):54-64. Published online February 1, 2001

1,266 View
18 Download

Abstract PDF: BACKGROUND
Conventional biochemical screening for family members with hereditary medullary thyroid cancer (MTC) is associated with problems of sensitivity and, specificity and it frequently detects gene carriers only after disease progression. Molecular genetic screening tests that detect germ-line point mutations of the RET proto-oncogene has changed our approach to hereditary MTC. In this study we screened members of a large Korean family that had a history of hereditary MTC by a molecular genetic method and propose a therapeutic approach in managing the disorder. METHODS: Using DNA acquired from peripheral blood leukocytes of the index patient, we performed PCR and direct sequencing of exon 10 of the RET proto-oncogene. PCR-RFLP using an Mbo II restriction enzyme was performed on family members who were at risk of MTC according to the family pedigree. Basal serum calcitonin level was determined in family members who had a point mutation of the RET proto-oncogene and a pentagastrin stimulation test was performed in 3 members. RESULTS: Genetic analysis in the index case revealed a mutation in exon 10, codon 618 of the RET proto-oncogene (TGC to AGC). Out of 28 members who were at risk of MTC, 24 members participated in the screening test. 9 members tested positive for a mutation in the same chromosomal location as the index patient by PCR-RFLP. Basal serum calcitonins were above 100 pg/mL in 2 members. 3 members who had a RET point muatation but a normal basal serum calcitonin level participated in the pentagastrin stimulation test and the results were negative in all members. We found a small medullary thyroid carcinoma that had a diameter of 0.2 cm in a 16 years old boy according to a negative pentagastrin stimulation test and who had received a prophylactic total thyroidectomy. He had no evidence of a lymph node metastasis. CONCLUSION: We detected a germ-line mutation of the RET proto-oncogene in codon 618 of Exon 10 by a molecular genetic method in a family with a hereditary MTC and found 9 members that had a negative history of MTC but had a RET point mutation. There was a very small MTC found in a 16 years old boy who had a normal pentagastrin stimulation test result. Therefore, It is recommended that a prophylactic total thyroidectomy be performed as well as in members that have a mutation of the RET proto-oncogene because MTC can metastasize early in its disease course.'

First
Prev
Page of 1
Next
Last

Search