Fatal outcome of a young woman with papillary thyroid carcinoma and graves' disease: possible implication of "cross-signalling" mechanism
Autor(a) principal: | |
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Data de Publicação: | 2008 |
Outros Autores: | , , , , , |
Tipo de documento: | Relatório |
Idioma: | eng |
Título da fonte: | Arquivos Brasileiros de Endocrinologia & Metabologia (Online) |
Texto Completo: | http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0004-27302008000700018 |
Resumo: | A 29 yrs-old patient was referred to our hospital due to generalized convulsions. She had hyperthyroidism treated with methimazole. Her MRI showed 4 metastatic lesions in the brain. She had a goiter with a "cold" nodule and a palpable ipsilateral lymph node. The FNAB disclosed a papillary thyroid carcinoma. Under 5 mg of MMI treatment, she had a subclinical hyperthyroidism and TRAb were 47.8% (n.v. < 10%). The CT scan also showed lung metastasis. She underwent a total thyroidectomy with a modified neck dissection and she received an accumulated radioiodine dose of 700 mCi during the following two years. She died from the consequences of multiple metastatic lesions. Studies were performed in DNA extracted from paraffin-embedded tissue from the tumor, the metastatic lymph node and the non-tumoral thyroid. The genetic analysis of tumoral DNA revealed point mutations in two different genes: the wild type CAA at codon 61 of N-RAS mutated to CAT, replacing glycine by histidine (G61H) and the normal GCC sequence at codon 623 of the TSHR gene was replaced by TCC, changing the alanine by serine (A623S). In the non-tumoral tissue no mutations were found. In vitro studies showed a constitutive activation of the TSHR. It is very probable that this activating mutation of the TSHR is unable to reach the end point of the PKA cascade in the tumoral tissue. One possibility that could explain this is the presence of a cross-signaling mechanism generating a deviation of the TSH receptor cascade to the more proliferative one involving the MAPKinase, giving perhaps a more aggressive behavior of this papillary thyroid cancer. |
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Fatal outcome of a young woman with papillary thyroid carcinoma and graves' disease: possible implication of "cross-signalling" mechanismThyroid, cancerTSHReceptorMutationN-RASGravesA 29 yrs-old patient was referred to our hospital due to generalized convulsions. She had hyperthyroidism treated with methimazole. Her MRI showed 4 metastatic lesions in the brain. She had a goiter with a "cold" nodule and a palpable ipsilateral lymph node. The FNAB disclosed a papillary thyroid carcinoma. Under 5 mg of MMI treatment, she had a subclinical hyperthyroidism and TRAb were 47.8% (n.v. < 10%). The CT scan also showed lung metastasis. She underwent a total thyroidectomy with a modified neck dissection and she received an accumulated radioiodine dose of 700 mCi during the following two years. She died from the consequences of multiple metastatic lesions. Studies were performed in DNA extracted from paraffin-embedded tissue from the tumor, the metastatic lymph node and the non-tumoral thyroid. The genetic analysis of tumoral DNA revealed point mutations in two different genes: the wild type CAA at codon 61 of N-RAS mutated to CAT, replacing glycine by histidine (G61H) and the normal GCC sequence at codon 623 of the TSHR gene was replaced by TCC, changing the alanine by serine (A623S). In the non-tumoral tissue no mutations were found. In vitro studies showed a constitutive activation of the TSHR. It is very probable that this activating mutation of the TSHR is unable to reach the end point of the PKA cascade in the tumoral tissue. One possibility that could explain this is the presence of a cross-signaling mechanism generating a deviation of the TSH receptor cascade to the more proliferative one involving the MAPKinase, giving perhaps a more aggressive behavior of this papillary thyroid cancer.Sociedade Brasileira de Endocrinologia e Metabologia2008-10-01info:eu-repo/semantics/reportinfo:eu-repo/semantics/publishedVersiontext/htmlhttp://old.scielo.br/scielo.php?script=sci_arttext&pid=S0004-27302008000700018Arquivos Brasileiros de Endocrinologia & Metabologia v.52 n.7 2008reponame:Arquivos Brasileiros de Endocrinologia & Metabologia (Online)instname:Sociedade Brasileira de Endocrinologia e Metabologia (SBEM)instacron:SBEM10.1590/S0004-27302008000700018info:eu-repo/semantics/openAccessCross,Graciela A. deSuarez,HoracioPitoia,FabiánMoncet,DanielVanegas,MaríaBruno,Oscar D.Niepomniszcze,Hugoeng2008-12-04T00:00:00Zoai:scielo:S0004-27302008000700018Revistahttps://www.aem-sbem.com/ONGhttps://old.scielo.br/oai/scielo-oai.php||abem-editoria@endocrino.org.br1677-94870004-2730opendoar:2008-12-04T00:00Arquivos Brasileiros de Endocrinologia & Metabologia (Online) - Sociedade Brasileira de Endocrinologia e Metabologia (SBEM)false |
dc.title.none.fl_str_mv |
Fatal outcome of a young woman with papillary thyroid carcinoma and graves' disease: possible implication of "cross-signalling" mechanism |
title |
Fatal outcome of a young woman with papillary thyroid carcinoma and graves' disease: possible implication of "cross-signalling" mechanism |
spellingShingle |
Fatal outcome of a young woman with papillary thyroid carcinoma and graves' disease: possible implication of "cross-signalling" mechanism Cross,Graciela A. de Thyroid, cancer TSH Receptor Mutation N-RAS Graves |
title_short |
Fatal outcome of a young woman with papillary thyroid carcinoma and graves' disease: possible implication of "cross-signalling" mechanism |
title_full |
Fatal outcome of a young woman with papillary thyroid carcinoma and graves' disease: possible implication of "cross-signalling" mechanism |
title_fullStr |
Fatal outcome of a young woman with papillary thyroid carcinoma and graves' disease: possible implication of "cross-signalling" mechanism |
title_full_unstemmed |
Fatal outcome of a young woman with papillary thyroid carcinoma and graves' disease: possible implication of "cross-signalling" mechanism |
title_sort |
Fatal outcome of a young woman with papillary thyroid carcinoma and graves' disease: possible implication of "cross-signalling" mechanism |
author |
Cross,Graciela A. de |
author_facet |
Cross,Graciela A. de Suarez,Horacio Pitoia,Fabián Moncet,Daniel Vanegas,María Bruno,Oscar D. Niepomniszcze,Hugo |
author_role |
author |
author2 |
Suarez,Horacio Pitoia,Fabián Moncet,Daniel Vanegas,María Bruno,Oscar D. Niepomniszcze,Hugo |
author2_role |
author author author author author author |
dc.contributor.author.fl_str_mv |
Cross,Graciela A. de Suarez,Horacio Pitoia,Fabián Moncet,Daniel Vanegas,María Bruno,Oscar D. Niepomniszcze,Hugo |
dc.subject.por.fl_str_mv |
Thyroid, cancer TSH Receptor Mutation N-RAS Graves |
topic |
Thyroid, cancer TSH Receptor Mutation N-RAS Graves |
description |
A 29 yrs-old patient was referred to our hospital due to generalized convulsions. She had hyperthyroidism treated with methimazole. Her MRI showed 4 metastatic lesions in the brain. She had a goiter with a "cold" nodule and a palpable ipsilateral lymph node. The FNAB disclosed a papillary thyroid carcinoma. Under 5 mg of MMI treatment, she had a subclinical hyperthyroidism and TRAb were 47.8% (n.v. < 10%). The CT scan also showed lung metastasis. She underwent a total thyroidectomy with a modified neck dissection and she received an accumulated radioiodine dose of 700 mCi during the following two years. She died from the consequences of multiple metastatic lesions. Studies were performed in DNA extracted from paraffin-embedded tissue from the tumor, the metastatic lymph node and the non-tumoral thyroid. The genetic analysis of tumoral DNA revealed point mutations in two different genes: the wild type CAA at codon 61 of N-RAS mutated to CAT, replacing glycine by histidine (G61H) and the normal GCC sequence at codon 623 of the TSHR gene was replaced by TCC, changing the alanine by serine (A623S). In the non-tumoral tissue no mutations were found. In vitro studies showed a constitutive activation of the TSHR. It is very probable that this activating mutation of the TSHR is unable to reach the end point of the PKA cascade in the tumoral tissue. One possibility that could explain this is the presence of a cross-signaling mechanism generating a deviation of the TSH receptor cascade to the more proliferative one involving the MAPKinase, giving perhaps a more aggressive behavior of this papillary thyroid cancer. |
publishDate |
2008 |
dc.date.none.fl_str_mv |
2008-10-01 |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/report |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
format |
report |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0004-27302008000700018 |
url |
http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0004-27302008000700018 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
10.1590/S0004-27302008000700018 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
text/html |
dc.publisher.none.fl_str_mv |
Sociedade Brasileira de Endocrinologia e Metabologia |
publisher.none.fl_str_mv |
Sociedade Brasileira de Endocrinologia e Metabologia |
dc.source.none.fl_str_mv |
Arquivos Brasileiros de Endocrinologia & Metabologia v.52 n.7 2008 reponame:Arquivos Brasileiros de Endocrinologia & Metabologia (Online) instname:Sociedade Brasileira de Endocrinologia e Metabologia (SBEM) instacron:SBEM |
instname_str |
Sociedade Brasileira de Endocrinologia e Metabologia (SBEM) |
instacron_str |
SBEM |
institution |
SBEM |
reponame_str |
Arquivos Brasileiros de Endocrinologia & Metabologia (Online) |
collection |
Arquivos Brasileiros de Endocrinologia & Metabologia (Online) |
repository.name.fl_str_mv |
Arquivos Brasileiros de Endocrinologia & Metabologia (Online) - Sociedade Brasileira de Endocrinologia e Metabologia (SBEM) |
repository.mail.fl_str_mv |
||abem-editoria@endocrino.org.br |
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1754734810101710848 |