Prophylactic Thyroidectomy in Multiple Endocrine Neoplasia Type 2A

Skinner, Michael A.; Moley, Jeffrey; Dilley, William G.; Owzar, Kouros; DeBenedetti, Mary K.; Wells, Samuel A.

doi:10.1056/nejmoa043999

Cited by 330 publications

(243 citation statements)

References 21 publications

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“…• For carriers of high-and moderate-risk mutations (ATA categories H and MOD; classic and atypical MEN2A), nodal spread is very rarely present before the age of 10 years (Skinner et al 2005, Elisei et al 2012.…”

Section: Transformation Of the Thyroid Glandmentioning

confidence: 99%

Advances in risk-oriented surgery for multiple endocrine neoplasia type 2

Machens¹,

Dralle²

2018

Endocrine-Related Cancer

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Genetic association studies hinge on definite clinical case definitions of the disease of interest. This is why more penetrant mutations were overrepresented in early multiple endocrine neoplasia type 2 (MEN2) studies, whereas less penetrant mutations went underrepresented. Enrichment of genetic association studies with advanced disease may produce a flawed understanding of disease evolution, precipitating far-reaching surgical strategies like bilateral total adrenalectomy and 4-gland parathyroidectomy in MEN2. The insight into the natural course of the disease gleaned over the past 25 years caused a paradigm shift in MEN2: from the removal of target organs at the expense of greater operative morbidity to close biochemical surveillance and targeted resection of adrenal tumors and hyperplastic parathyroid glands. The lead time provided by early identification of asymptomatic MEN2 carriers under biochemical surveillance delimits a 'window of opportunity', within which (i) pre-emptive total thyroidectomy alone is adequate, circumventing morbidity attendant to central node dissection; (ii) subtotal 'tissue-sparing' adrenalectomy is sufficient, trading the risk of steroid dependency for the risk of a second pheochromocytoma in the adrenal remnant and (iii) parathyroidectomy is limited to enlarged glands, trading the risk of postoperative hypoparathyroidism for the risk of leaving behind hyperactive parathyroid glands. Future research should delineate further the mutation-specific, age-dependent penetrance of pheochromocytoma and primary hyperparathyroidism to refine the risk-oriented approach to MEN2. The sweeping changes in the management of MEN2 since the new millenium hold the hope that death and major morbidity from this uncommon disease can be eliminated in our lifetime.

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Section: Transformation Of the Thyroid Glandmentioning

confidence: 99%

Advances in risk-oriented surgery for multiple endocrine neoplasia type 2

Machens¹,

Dralle²

2018

Endocrine-Related Cancer

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“…This is the case with the use of prophylactic thyroidectomy for persons with pathogenic RET mutations because family studies have demonstrated previously a high penetrance for these mutations 55 . Additionally, a recent review indicates that requiring RCTs in conjunction with current evidence-based medicine classification of data quality to assess diagnostic criteria is inadequate, proposing that alternative scales are needed to determine the value of pathology results outside of the limited scope of evaluating RCT drug trial outcomes for prognostic and predictive data 56 .…”

Section: Recommendations Alternatives To Randomized Controlled Trialsmentioning

confidence: 99%

The Spectrum of Clinical Utilities in Molecular Pathology Testing Procedures for Inherited Conditions and Cancer

Joseph

Cankovic

Caughron³

et al. 2016

The Journal of Molecular Diagnostics

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“…MTC may occur sporadically (in about 75% of cases) or as a part of the autosomal dominantly inherited cancer syndrome, known as multiple endocrine neoplasia type 2 (MEN 2) (Mulligan et al, 1993;Eng, 1999;Frank-Raue et al, 2007). MTC is the most common cause of death in patients with MEN 2 (Skinner et al, 2005). This familial type of thyroid carcinoma usually originates as multifocal C-cell hyperplasia, its progression to MTC is extremely variable, and may take several years (Carling, 2005).…”

mentioning

confidence: 99%

Correlation of RET somatic mutations with clinicopathological features in sporadic medullary thyroid carcinomas

Moura¹,

Cavaco²,

Pinto³

et al. 2009

Br J Cancer

154

124

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Screening of REarranged during Transfection (RET) gene mutations has been carried out in different series of sporadic medullary thyroid carcinomas (MTC). RET-positive tumours seem to be associated to a worse clinical outcome. However, the correlation between the type of RET mutation and the patients' clinicopathological data has not been evaluated yet. We analysed RET exons 5, 8, 10 -16 in fifty-one sporadic MTC, and found somatic mutations in thirty-three (64.7%) tumours. Among the RET-positive cases, exon 16 was the most frequently affected (60.6%). Two novel somatic mutations (Cys630Gly, c.1881del18) were identified. MTC patients were divided into three groups: group 1, with mutations in RET exons 15 and 16; group 2, with other RET mutations; group 3, having no RET mutations. Group 1 had higher prevalence (P ¼ 0.0051) and number of lymph node metastases (P ¼ 0.0017), and presented more often multifocal tumours (P ¼ 0.037) and persistent disease at last control (P ¼ 0.0242) than group 2. Detectable serum calcitonin levels at last screening (P ¼ 0.0119) and stage IV disease (P ¼ 0.0145) were more frequent in group 1, than in the other groups. Our results suggest that, among the sporadic MTC, cases with RET mutations in exons 15 and 16 are associated with the worst prognosis. Cases with other RET mutations have the most indolent course, and those with no RET mutations have an intermediate risk.

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Prophylactic Thyroidectomy in Multiple Endocrine Neoplasia Type 2A

Cited by 330 publications

References 21 publications

Advances in risk-oriented surgery for multiple endocrine neoplasia type 2

Advances in risk-oriented surgery for multiple endocrine neoplasia type 2

The Spectrum of Clinical Utilities in Molecular Pathology Testing Procedures for Inherited Conditions and Cancer

Correlation of RET somatic mutations with clinicopathological features in sporadic medullary thyroid carcinomas

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