Transplante alogênico de paratireoide de doador vivo como tratamento do hipoparatireoidismo pós-cirúrgico persistente

Detalhes bibliográficos
Ano de defesa: 2023
Autor(a) principal: Gadelha, Daniel Duarte
Orientador(a): Montenegro Júnior, Renan Magalhães
Banca de defesa: Não Informado pela instituição
Tipo de documento: Tese
Tipo de acesso: Acesso aberto
Idioma: por
Instituição de defesa: Não Informado pela instituição
Programa de Pós-Graduação: Não Informado pela instituição
Departamento: Não Informado pela instituição
País: Não Informado pela instituição
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 Thus, this study aimed at implementing a viable parathyroid allotransplantation protocol, still unpublished in Brazil and applicable to patients who have severe hypoparathyroidism, refractory to conventional treatment.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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spelling 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.
publishDate 2023
dc.date.accessioned.fl_str_mv 2023-10-05T20:51:04Z
dc.date.available.fl_str_mv 2023-10-05T20:51:04Z
dc.date.issued.fl_str_mv 2023
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dc.identifier.citation.fl_str_mv 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.
dc.identifier.uri.fl_str_mv http://repositorio.ufc.br/handle/riufc/74600
identifier_str_mv 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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