Transplante alogênico de paratireoide de doador vivo como tratamento do hipoparatireoidismo pós-cirúrgico persistente
| Ano de defesa: | 2023 |
|---|---|
| Autor(a) principal: | |
| Orientador(a): | |
| Banca de defesa: | |
| Tipo de documento: | Tese |
| Tipo de acesso: | Acesso aberto |
| Idioma: | por |
| Instituição de defesa: |
Não Informado pela instituição
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| Programa de Pós-Graduação: |
Não Informado pela instituição
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| Departamento: |
Não Informado pela instituição
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| País: |
Não Informado pela instituição
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| Área do conhecimento CNPq: | |
| Link de acesso: | http://repositorio.ufc.br/handle/riufc/74600 |
Resumo: | Hypoparathyroidism is a disorder characterized by deficient or inappropriately low parathyroid hormone (PTH) secretion, leading to hypocalcemia and hyperphosphatemia. The standard clinical treatment has been used for decades, which consists of calcium and vitamin (calcitriol) replacement. However, this treatment shows inefficacy, leading to maintenance or worsening of the conditions already related to hypoparathyroidism (fatigue, muscle cramps, paresthesia, seizures, intracerebral calcifications, cognitive dysfunction, and renal stones/nephrocalcinosis). Therapies based on recombinant human parathyroid hormone (rhPTH) have emerged in recent years but still have low availability mainly due to their high cost. Despite few reports in the literature, parathyroid allotransplantation has been described as an alternative strategy to treat more severe cases. Thus, this study aimed at implementing a viable parathyroid allotransplantation protocol, still unpublished in Brazil and applicable to patients who have severe hypoparathyroidism, refractory to conventional treatment. The patients recruited as donors had end-stage chronic kidney disease and hyperparathyroidism awaiting for surgery. Parathyroid tissue was removed, prepared and immediately implanted in the non-dominant forearm of the recipient. Donors and recipients were ABO-compatible, and immunological screening was performed in two cases (HLA typing, Panel Reactive Antibody, and crossmatch tests). A short-term immunosuppressive regimen was adopted, which consists of three days of methylprednisolone followed by seven days of prednisone. The first allograft showed no evidence of functionality 12 months after transplant. In the following two patients, serum PTH levels did not increased as expected. However, serum calcium levels increased, and both patients experienced relief from hypocalcemic symptoms. In Case 2, oral supplementation decreased to half of the initial dose one month after transplantation and to one-fifth at the end of a 12-month follow-up period. In Case 3, intravenous calcium could be discontinued one week post-transplantation, and it was not yet required. PTH levels increased in Case 4 and hypocalcemic symptoms also reduced. No serious adverse events were observed. In conclusion, parathyroid allotransplantation showed to be safe and effective, and it can be considered for severe hypoparathyroidism. This is an innovative and not yet described procedure in Brazil. The procedure demonstrates to be an excellent option of treatment for refractory cases and it has the advantage of being low cost. Further studies with longer follow-up and greater number of patients are needed to confirm such efficacy in the long term. |
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Gadelha, Daniel DuarteMontenegro Júnior, Renan Magalhães2023-10-05T20:51:04Z2023-10-05T20:51:04Z2023GADELHA, Daniel Duarte. Transplante alogênico de paratireoide de doador vivo como tratamento do hipoparatireoidismo pós-cirúrgico persistente. 2023. 109 f. Tese (Doutorado em Biotecnologia) - Universidade Federal do Ceará, Fortaleza, 2023.http://repositorio.ufc.br/handle/riufc/74600Hypoparathyroidism is a disorder characterized by deficient or inappropriately low parathyroid hormone (PTH) secretion, leading to hypocalcemia and hyperphosphatemia. The standard clinical treatment has been used for decades, which consists of calcium and vitamin (calcitriol) replacement. However, this treatment shows inefficacy, leading to maintenance or worsening of the conditions already related to hypoparathyroidism (fatigue, muscle cramps, paresthesia, seizures, intracerebral calcifications, cognitive dysfunction, and renal stones/nephrocalcinosis). Therapies based on recombinant human parathyroid hormone (rhPTH) have emerged in recent years but still have low availability mainly due to their high cost. Despite few reports in the literature, parathyroid allotransplantation has been described as an alternative strategy to treat more severe cases. Thus, this study aimed at implementing a viable parathyroid allotransplantation protocol, still unpublished in Brazil and applicable to patients who have severe hypoparathyroidism, refractory to conventional treatment. The patients recruited as donors had end-stage chronic kidney disease and hyperparathyroidism awaiting for surgery. Parathyroid tissue was removed, prepared and immediately implanted in the non-dominant forearm of the recipient. Donors and recipients were ABO-compatible, and immunological screening was performed in two cases (HLA typing, Panel Reactive Antibody, and crossmatch tests). A short-term immunosuppressive regimen was adopted, which consists of three days of methylprednisolone followed by seven days of prednisone. The first allograft showed no evidence of functionality 12 months after transplant. In the following two patients, serum PTH levels did not increased as expected. However, serum calcium levels increased, and both patients experienced relief from hypocalcemic symptoms. In Case 2, oral supplementation decreased to half of the initial dose one month after transplantation and to one-fifth at the end of a 12-month follow-up period. In Case 3, intravenous calcium could be discontinued one week post-transplantation, and it was not yet required. PTH levels increased in Case 4 and hypocalcemic symptoms also reduced. No serious adverse events were observed. In conclusion, parathyroid allotransplantation showed to be safe and effective, and it can be considered for severe hypoparathyroidism. This is an innovative and not yet described procedure in Brazil. The procedure demonstrates to be an excellent option of treatment for refractory cases and it has the advantage of being low cost. Further studies with longer follow-up and greater number of patients are needed to confirm such efficacy in the long term.O hipoparatireoidismo é um distúrbio caracterizado pela secreção deficiente ou inapropriada de paratormônio (PTH), levando a hipocalcemia e hiperfosfatemia. O tratamento padrão tem sido usado durante décadas, que consiste na reposição de cálcio e de vitamina D (calcitriol). Entretanto, tal tratamento mostra-se ineficaz, levando à manutenção ou agravamento das condições já relacionadas ao hipoparatireoidismo (fadiga, cãibras, parestesias, convulsões, calcificações intracerebrais, disfunção cognitiva e nefrolitíase / nefrocalcinose). As terapias baseadas no PTH recombinante humano (rhPTH) vem emergindo nos últimos anos, mas ainda têm baixa viabilidade devido, principalmente, ao seu alto custo. Apesar de escassos relatos na literatura, o alotransplante de paratireoide tem sido descrito como uma estratégia alternativa de tratamento para os casos mais graves. Assim, o presente estudo propôs implementar um protocolo de alotransplante de paratireoide viável e de forma inédita no Brasil, tendo como indicação pacientes com hipoparatireoidismo grave, refratários ao tratamento convencional. Os pacientes recrutados como doadores tinham doença renal crônica terminal e hiperparatireoidismo com indicação de tratamento cirúrgico. O tecido paratireoideano foi removido, preparado e imediatamente implantado no antebraço não dominante do receptor. Doadores e receptores foram ABO compatíveis e o rastreamento imunológico foi realizado em dois casos (tipificação HLA, Painel de Reatividade a Anticorpos e Prova Cruzada). Um esquema de imunossupressão de curto prazo foi adotado, consistindo em três dias de metilprednisolona seguidos por sete dias de prednisona. O primeiro aloenxerto não mostrou evidência de funcionalidade 12 meses após o transplante. Nas duas pacientes seguintes os níveis séricos de PTH não aumentaram como esperado. Entretanto, os níveis séricos de cálcio aumentaram e ambas as pacientes constataram alívio dos sintomas hipocalcêmicos. No Caso 2, a suplementação oral reduziu para metade da dose inicial um mês após o transplante, e para um quinto ao final de 12 meses de seguimento. No caso 3, a administração de cálcio intravenoso pôde ser descontinuada uma semana após o transplante e não foi mais necessária. Os níveis de PTH aumentaram no Caso 4 e os sintomas hipocalcêmicos também reduziram. Nenhum efeito adverso grave foi observado. Em conclusão, o alotransplante de paratireoide mostrou-se seguro e eficaz, podendo ser considerado nos casos graves de hipoparatireoidismo. Este é um procedimento inovador que ainda não foi descrito no Brasil. O procedimento mostra-se como uma excelente opção de tratamento nos casos refratários e com a vantagem de ter um baixo custo. Estudos adicionais com seguimento prolongado e com maior casuística são necessários para confirmar tal eficácia a longo prazo.Transplante alogênico de paratireoide de doador vivo como tratamento do hipoparatireoidismo pós-cirúrgico persistenteLiving-donor parathyroid allotransplantation as treatment for postsurgical persistent hypoparathyroidisminfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisAloenxertosHipocalcemiaHipoparatireoidismoTransplante de TecidosAllypocalcemiaHthyroidismHthyroidismTissue transplantCNPQ::CIENCIAS BIOLOGICASinfo:eu-repo/semantics/openAccessporreponame:Repositório Institucional da Universidade Federal do Ceará (UFC)instname:Universidade Federal do Ceará (UFC)instacron:UFChttp://lattes.cnpq.br/6519372563123911https://orcid.org/0000-0001-7287-8726http://lattes.cnpq.br/74924504329423972023-10-05LICENSElicense.txtlicense.txttext/plain; charset=utf-81748http://repositorio.ufc.br/bitstream/riufc/74600/4/license.txt8a4605be74aa9ea9d79846c1fba20a33MD54ORIGINAL2023_tese_ddgadelha.pdf2023_tese_ddgadelha.pdfapplication/pdf4882613http://repositorio.ufc.br/bitstream/riufc/74600/5/2023_tese_ddgadelha.pdf67d9d20259068633d2a9db2ab2177a1fMD55riufc/746002023-10-05 17:52:18.199oai:repositorio.ufc.br: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Repositório InstitucionalPUBhttp://www.repositorio.ufc.br/ri-oai/requestbu@ufc.br || repositorio@ufc.bropendoar:2023-10-05T20:52:18Repositório Institucional da Universidade Federal do Ceará (UFC) - Universidade Federal do Ceará (UFC)false |
| dc.title.pt_BR.fl_str_mv |
Transplante alogênico de paratireoide de doador vivo como tratamento do hipoparatireoidismo pós-cirúrgico persistente |
| dc.title.en.pt_BR.fl_str_mv |
Living-donor parathyroid allotransplantation as treatment for postsurgical persistent hypoparathyroidism |
| title |
Transplante alogênico de paratireoide de doador vivo como tratamento do hipoparatireoidismo pós-cirúrgico persistente |
| spellingShingle |
Transplante alogênico de paratireoide de doador vivo como tratamento do hipoparatireoidismo pós-cirúrgico persistente Gadelha, Daniel Duarte CNPQ::CIENCIAS BIOLOGICAS Aloenxertos Hipocalcemia Hipoparatireoidismo Transplante de Tecidos Allypocalcemia Hthyroidism Hthyroidism Tissue transplant |
| title_short |
Transplante alogênico de paratireoide de doador vivo como tratamento do hipoparatireoidismo pós-cirúrgico persistente |
| title_full |
Transplante alogênico de paratireoide de doador vivo como tratamento do hipoparatireoidismo pós-cirúrgico persistente |
| title_fullStr |
Transplante alogênico de paratireoide de doador vivo como tratamento do hipoparatireoidismo pós-cirúrgico persistente |
| title_full_unstemmed |
Transplante alogênico de paratireoide de doador vivo como tratamento do hipoparatireoidismo pós-cirúrgico persistente |
| title_sort |
Transplante alogênico de paratireoide de doador vivo como tratamento do hipoparatireoidismo pós-cirúrgico persistente |
| author |
Gadelha, Daniel Duarte |
| author_facet |
Gadelha, Daniel Duarte |
| author_role |
author |
| dc.contributor.author.fl_str_mv |
Gadelha, Daniel Duarte |
| dc.contributor.advisor1.fl_str_mv |
Montenegro Júnior, Renan Magalhães |
| contributor_str_mv |
Montenegro Júnior, Renan Magalhães |
| dc.subject.cnpq.fl_str_mv |
CNPQ::CIENCIAS BIOLOGICAS |
| topic |
CNPQ::CIENCIAS BIOLOGICAS Aloenxertos Hipocalcemia Hipoparatireoidismo Transplante de Tecidos Allypocalcemia Hthyroidism Hthyroidism Tissue transplant |
| dc.subject.ptbr.pt_BR.fl_str_mv |
Aloenxertos Hipocalcemia Hipoparatireoidismo Transplante de Tecidos |
| dc.subject.en.pt_BR.fl_str_mv |
Allypocalcemia Hthyroidism Hthyroidism Tissue transplant |
| description |
Hypoparathyroidism is a disorder characterized by deficient or inappropriately low parathyroid hormone (PTH) secretion, leading to hypocalcemia and hyperphosphatemia. The standard clinical treatment has been used for decades, which consists of calcium and vitamin (calcitriol) replacement. However, this treatment shows inefficacy, leading to maintenance or worsening of the conditions already related to hypoparathyroidism (fatigue, muscle cramps, paresthesia, seizures, intracerebral calcifications, cognitive dysfunction, and renal stones/nephrocalcinosis). Therapies based on recombinant human parathyroid hormone (rhPTH) have emerged in recent years but still have low availability mainly due to their high cost. Despite few reports in the literature, parathyroid allotransplantation has been described as an alternative strategy to treat more severe cases. Thus, this study aimed at implementing a viable parathyroid allotransplantation protocol, still unpublished in Brazil and applicable to patients who have severe hypoparathyroidism, refractory to conventional treatment. The patients recruited as donors had end-stage chronic kidney disease and hyperparathyroidism awaiting for surgery. Parathyroid tissue was removed, prepared and immediately implanted in the non-dominant forearm of the recipient. Donors and recipients were ABO-compatible, and immunological screening was performed in two cases (HLA typing, Panel Reactive Antibody, and crossmatch tests). A short-term immunosuppressive regimen was adopted, which consists of three days of methylprednisolone followed by seven days of prednisone. The first allograft showed no evidence of functionality 12 months after transplant. In the following two patients, serum PTH levels did not increased as expected. However, serum calcium levels increased, and both patients experienced relief from hypocalcemic symptoms. In Case 2, oral supplementation decreased to half of the initial dose one month after transplantation and to one-fifth at the end of a 12-month follow-up period. In Case 3, intravenous calcium could be discontinued one week post-transplantation, and it was not yet required. PTH levels increased in Case 4 and hypocalcemic symptoms also reduced. No serious adverse events were observed. In conclusion, parathyroid allotransplantation showed to be safe and effective, and it can be considered for severe hypoparathyroidism. This is an innovative and not yet described procedure in Brazil. The procedure demonstrates to be an excellent option of treatment for refractory cases and it has the advantage of being low cost. Further studies with longer follow-up and greater number of patients are needed to confirm such efficacy in the long term. |
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2023 |
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2023-10-05T20:51:04Z |
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2023-10-05T20:51:04Z |
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2023 |
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GADELHA, Daniel Duarte. Transplante alogênico de paratireoide de doador vivo como tratamento do hipoparatireoidismo pós-cirúrgico persistente. 2023. 109 f. Tese (Doutorado em Biotecnologia) - Universidade Federal do Ceará, Fortaleza, 2023. |
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http://repositorio.ufc.br/handle/riufc/74600 |
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GADELHA, Daniel Duarte. Transplante alogênico de paratireoide de doador vivo como tratamento do hipoparatireoidismo pós-cirúrgico persistente. 2023. 109 f. Tese (Doutorado em Biotecnologia) - Universidade Federal do Ceará, Fortaleza, 2023. |
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