Cargando…
What Lies behind Paraneoplastic Hypercalcemia Secondary to Well-Differentiated Neuroendocrine Neoplasms? A Systematic Review of the Literature
Background: Neuroendocrine neoplasms (NEN) originate from neuroendocrine cells ubiquitously spread throughout the body. Hypercalcemia associated with cancer is the most common life-threatening metabolic disorder in patients with advanced stage cancer. Paraneoplastic hypercalcemia is more commonly as...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9604936/ https://www.ncbi.nlm.nih.gov/pubmed/36294693 http://dx.doi.org/10.3390/jpm12101553 |
_version_ | 1784817940510539776 |
---|---|
author | Giannetta, Elisa Sesti, Franz Modica, Roberta Grossrubatscher, Erika Maria Ragni, Alberto Zanata, Isabella Colao, Annamaria Faggiano, Antongiulio |
author_facet | Giannetta, Elisa Sesti, Franz Modica, Roberta Grossrubatscher, Erika Maria Ragni, Alberto Zanata, Isabella Colao, Annamaria Faggiano, Antongiulio |
author_sort | Giannetta, Elisa |
collection | PubMed |
description | Background: Neuroendocrine neoplasms (NEN) originate from neuroendocrine cells ubiquitously spread throughout the body. Hypercalcemia associated with cancer is the most common life-threatening metabolic disorder in patients with advanced stage cancer. Paraneoplastic hypercalcemia is more commonly associated with hematological malignancies, renal and breast carcinomas, and squamous cell carcinomas, but it has also been described in patients with well-differentiated NEN, where it often remains undiagnosed. Among its causes, systemic secretion of parathyroid hormone-related protein (PTHrP) and ectopic production of 1,25-dihydroxyvitamin D and parathyroid hormone (PTH) may be considered paraneoplastic causes of hypercalcemia. In order to clarify the diagnostic work up of paraneoplastic hypercalcemia in patients with NEN, we perform a systematic review, which is lacking in the literature. Methods: We performed a data search using MEDLINE and SCOPUS including papers from 1961 to 2021. We selected articles on paraneoplastic hypercalcemia associated with well-differentiated NEN. Results: The search led to the selection of 78 publications for a total of 114 patients. Pooled data showed that the most frequent primary tumor site associated with paraneoplastic hypercalcemia was pancreatic NEN, followed by Pheochromocytoma. In most cases, paraneoplastic hypercalcemia was caused by PTHrP production and secretion. In more than two thirds of cases, paraneoplastic hypercalcemia was present at the time of NEN diagnosis and, in metachronous cases, was related to local recurrence, distant metastasis development, or tumor progression. In most patients, a combination of therapeutic approaches was employed, and reduction of the tumor burden was essential to control the paraneoplastic syndrome. Discussion: The onset of hypercalcemia associated with cancer in patients with well-differentiated NEN represents a major clinical challenge. The complex clinical and therapeutical management of paraneoplastic hypercalcemia implies the need for a multidisciplinary approach, aimed at controlling the clinical syndrome and tumor growth. |
format | Online Article Text |
id | pubmed-9604936 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-96049362022-10-27 What Lies behind Paraneoplastic Hypercalcemia Secondary to Well-Differentiated Neuroendocrine Neoplasms? A Systematic Review of the Literature Giannetta, Elisa Sesti, Franz Modica, Roberta Grossrubatscher, Erika Maria Ragni, Alberto Zanata, Isabella Colao, Annamaria Faggiano, Antongiulio J Pers Med Systematic Review Background: Neuroendocrine neoplasms (NEN) originate from neuroendocrine cells ubiquitously spread throughout the body. Hypercalcemia associated with cancer is the most common life-threatening metabolic disorder in patients with advanced stage cancer. Paraneoplastic hypercalcemia is more commonly associated with hematological malignancies, renal and breast carcinomas, and squamous cell carcinomas, but it has also been described in patients with well-differentiated NEN, where it often remains undiagnosed. Among its causes, systemic secretion of parathyroid hormone-related protein (PTHrP) and ectopic production of 1,25-dihydroxyvitamin D and parathyroid hormone (PTH) may be considered paraneoplastic causes of hypercalcemia. In order to clarify the diagnostic work up of paraneoplastic hypercalcemia in patients with NEN, we perform a systematic review, which is lacking in the literature. Methods: We performed a data search using MEDLINE and SCOPUS including papers from 1961 to 2021. We selected articles on paraneoplastic hypercalcemia associated with well-differentiated NEN. Results: The search led to the selection of 78 publications for a total of 114 patients. Pooled data showed that the most frequent primary tumor site associated with paraneoplastic hypercalcemia was pancreatic NEN, followed by Pheochromocytoma. In most cases, paraneoplastic hypercalcemia was caused by PTHrP production and secretion. In more than two thirds of cases, paraneoplastic hypercalcemia was present at the time of NEN diagnosis and, in metachronous cases, was related to local recurrence, distant metastasis development, or tumor progression. In most patients, a combination of therapeutic approaches was employed, and reduction of the tumor burden was essential to control the paraneoplastic syndrome. Discussion: The onset of hypercalcemia associated with cancer in patients with well-differentiated NEN represents a major clinical challenge. The complex clinical and therapeutical management of paraneoplastic hypercalcemia implies the need for a multidisciplinary approach, aimed at controlling the clinical syndrome and tumor growth. MDPI 2022-09-21 /pmc/articles/PMC9604936/ /pubmed/36294693 http://dx.doi.org/10.3390/jpm12101553 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Systematic Review Giannetta, Elisa Sesti, Franz Modica, Roberta Grossrubatscher, Erika Maria Ragni, Alberto Zanata, Isabella Colao, Annamaria Faggiano, Antongiulio What Lies behind Paraneoplastic Hypercalcemia Secondary to Well-Differentiated Neuroendocrine Neoplasms? A Systematic Review of the Literature |
title | What Lies behind Paraneoplastic Hypercalcemia Secondary to Well-Differentiated Neuroendocrine Neoplasms? A Systematic Review of the Literature |
title_full | What Lies behind Paraneoplastic Hypercalcemia Secondary to Well-Differentiated Neuroendocrine Neoplasms? A Systematic Review of the Literature |
title_fullStr | What Lies behind Paraneoplastic Hypercalcemia Secondary to Well-Differentiated Neuroendocrine Neoplasms? A Systematic Review of the Literature |
title_full_unstemmed | What Lies behind Paraneoplastic Hypercalcemia Secondary to Well-Differentiated Neuroendocrine Neoplasms? A Systematic Review of the Literature |
title_short | What Lies behind Paraneoplastic Hypercalcemia Secondary to Well-Differentiated Neuroendocrine Neoplasms? A Systematic Review of the Literature |
title_sort | what lies behind paraneoplastic hypercalcemia secondary to well-differentiated neuroendocrine neoplasms? a systematic review of the literature |
topic | Systematic Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9604936/ https://www.ncbi.nlm.nih.gov/pubmed/36294693 http://dx.doi.org/10.3390/jpm12101553 |
work_keys_str_mv | AT giannettaelisa whatliesbehindparaneoplastichypercalcemiasecondarytowelldifferentiatedneuroendocrineneoplasmsasystematicreviewoftheliterature AT sestifranz whatliesbehindparaneoplastichypercalcemiasecondarytowelldifferentiatedneuroendocrineneoplasmsasystematicreviewoftheliterature AT modicaroberta whatliesbehindparaneoplastichypercalcemiasecondarytowelldifferentiatedneuroendocrineneoplasmsasystematicreviewoftheliterature AT grossrubatschererikamaria whatliesbehindparaneoplastichypercalcemiasecondarytowelldifferentiatedneuroendocrineneoplasmsasystematicreviewoftheliterature AT ragnialberto whatliesbehindparaneoplastichypercalcemiasecondarytowelldifferentiatedneuroendocrineneoplasmsasystematicreviewoftheliterature AT zanataisabella whatliesbehindparaneoplastichypercalcemiasecondarytowelldifferentiatedneuroendocrineneoplasmsasystematicreviewoftheliterature AT colaoannamaria whatliesbehindparaneoplastichypercalcemiasecondarytowelldifferentiatedneuroendocrineneoplasmsasystematicreviewoftheliterature AT faggianoantongiulio whatliesbehindparaneoplastichypercalcemiasecondarytowelldifferentiatedneuroendocrineneoplasmsasystematicreviewoftheliterature |