Codon-Specific Development of Pheochromocytoma in Multiple Endocrine Neoplasia Type 2

Machens, Andreas; Brauckhoff, Michael; Holzhausen, Hans-Jürgen; Thanh, Phuong Nguyen; Lehnert, Hendrik; Dralle, Henning

doi:10.1210/jc.2005-0064

Cited by 137 publications

(111 citation statements)

References 32 publications

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“…Because her calcitonin levels normalized after thyroidectomy and she had no evidence of recurrence 55 months postoperatively, she was considered node-negative. Six of the 38 patients also underwent adrenalectomy for pheochromocytoma at this institution or elsewhere (three patients each), as described previously (Machens et al 2005). Informed consent was obtained for each surgical procedure, all of which represented standard practice of care.…”

Section: Extent Of Surgerymentioning

confidence: 99%

Modification of multiple endocrine neoplasia 2A phenotype by cell membrane proximity of RET mutations in exon 10

Machens¹,

Hauptmann²,

Dralle³

2009

Endocrine-Related Cancer

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Rearranged during transfection (RET) germ-line mutations in exon 10 are peculiar because they produce both gain-of-function multiple endocrine neoplasia 2A and loss-of-function Hirschsprung's disease phenotypes. Drawing on 38 medullary thyroid cancer patients harboring germline mutations in codon 620 (nZ8), 618 (nZ19), 611 (nZ10), and 609 (nZ1), this study aimed to test the hypothesis that closer proximity of RET germ-line mutations in exon 10 to the cell membrane may translate into earlier or more advanced disease. The closer mutations in codon 620, 618, and 611 were located to the transmembrane domain (codons 657-636) of the RET receptor, the greater were mean primary tumor diameters (23.5, 18.7, and 7.5 mm, PZ0.020), the frequency of lymph node metastasis (75, 68, and 30%, PZ0.11) and pheochromocytoma (38, 16, and 0%, PZ0.11). Periods of observation were broadly comparable for these groups (mean age 33.4-39.3 years; PZ0.71). When mutations in adjoining codons were collapsed (codons 620/618 vs 611/609), the differences in mean primary tumor diameter (20.1 vs 7.4 mm, PZ0.005) and lymph node metastasis (70 vs 36%; PZ0.07) were accentuated. Compared with 80 carriers of exon 11 mutations (codon 634, nZ78; codon 630, nZ2), the 38 carriers of exon 10 mutations, which are rarer and confer a weaker transforming activity in vitro than exon 11 mutations, required significantly more time to develop fewer tumors. Although limited in numbers, these data suggested that membrane proximity is an important determinant of tumor development in carriers of RET mutations in exon 10.

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Section: Extent Of Surgerymentioning

confidence: 99%

Modification of multiple endocrine neoplasia 2A phenotype by cell membrane proximity of RET mutations in exon 10

Machens¹,

Hauptmann²,

Dralle³

2009

Endocrine-Related Cancer

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“…In MEN 2A, the onset of Pheo is usually concomitant or subsequent to MTC [10], but in 13-27% of cases it represents the first manifestation of the syndrome [9,11]; moreover it has also been reported a codon specific age-related onset of Pheo [12,13].…”

Section: Discussionmentioning

confidence: 99%

“…Negative post-operative urinary cathecolamines confirmed the radical resection. Serum calci- [12,13].…”

Section: Post-operative Evaluationmentioning

confidence: 99%

A novel RET gene mutation in a patient with apparently sporadic pheochromocytoma

et al. 2016

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“…The youngest ages at pheochromocytoma diagnosis were 12 and 5 years old in carriers of mutations in codons 918 and 634, respectively (72,112,113) …”

Section: (D)mentioning

confidence: 99%

“…An investigation of pheochromocytoma is mandatory in cases with suspected MEN 2 (72,74,140) (B/B/D) and is also indicated in individuals with apparently sporadic MTC that has not yet been subjected to RET molecular testing. Although the occurrence of pheochromocytoma is rather unlikely in these cases, its eventual identification before thyroid surgery is critical, as the complications that arise in undiagnosed cases are severe (72,74) …”

Section: Recommendationmentioning

confidence: 99%

Diagnóstico, tratamento e seguimento do carcinoma medular de tireoide: recomendações do Departamento de Tireoide da Sociedade Brasileira de Endocrinologia e Metabologia

Maia

Siqueira

Kulcsar

et al. 2014

Arq Bras Endocrinol Metab

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Introduction: Medullary thyroid carcinoma (MTC) originates in the thyroid parafollicular cells and represents 3-4% of the malignant neoplasms that affect this gland. Approximately 25% of these cases are hereditary due to activating mutations in the REarranged during Transfection (RET) proto-oncogene. The course of MTC is indolent, and survival rates depend on the tumor stage at diagnosis. The present article describes clinical evidence-based guidelines for the diagnosis, treatment, and follow-up of MTC. Objective: The aim of the consensus described herein, which was elaborated by Brazilian experts and sponsored by the Thyroid Department of the Brazilian Society of Endocrinology and Metabolism, was to discuss the diagnosis, treatment, and follow-up of individuals with MTC in accordance with the latest evidence reported in the literature. Materials and methods: After clinical questions were elaborated, the available literature was initially surveyed for evidence in the MedLine-PubMed database, followed by the Embase and Scientific Electronic Library Online/Latin American and Caribbean Health Science Literature (SciELO/Lilacs) databases. The strength of evidence was assessed according to the Oxford classification of evidence levels, which is based on study design, and the best evidence available for each question was selected. Results: Eleven questions corresponded to MTC diagnosis, 8 corresponded to its surgical treatment, and 13 corresponded to follow-up, for a total of 32 recommendations. The present article discusses the clinical and molecular diagnosis, initial surgical treatment, and postoperative management of MTC, as well as the therapeutic options for metastatic disease. Conclusions: MTC should be suspected in individuals who present with thyroid nodules and family histories of MTC, associations with pheochromocytoma and hyperparathyroidism, and/or typical phenotypic characteristics such as ganglioneuromatosis and Marfanoid habitus. Fine-needle nodule aspiration, serum calcitonin measurements, and anatomical-pathological examinations are useful for diagnostic confirmation. Surgery represents the only curative therapeutic strategy. The therapeutic options for metastatic disease remain limited and are restricted to disease control. Judicious postoperative assessments that focus on the identification of residual or recurrent disease are of paramount importance when defining the follow-up and later therapeutic management strategies. Arq Bras Endocrinol Metab. 2014;58(7):667-700

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Codon-Specific Development of Pheochromocytoma in Multiple Endocrine Neoplasia Type 2

Abstract: Based on these and published preliminary data, annual screening for pheochromocytoma may be warranted from age 10 yr in carriers of RET mutations in codons 918, 634, and 630, and from age 20 yr in the remainder.

Cited by 137 publications

References 32 publications

Modification of multiple endocrine neoplasia 2A phenotype by cell membrane proximity of RET mutations in exon 10

Modification of multiple endocrine neoplasia 2A phenotype by cell membrane proximity of RET mutations in exon 10

A novel RET gene mutation in a patient with apparently sporadic pheochromocytoma

Diagnóstico, tratamento e seguimento do carcinoma medular de tireoide: recomendações do Departamento de Tireoide da Sociedade Brasileira de Endocrinologia e Metabologia

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