Case Report: Unmasking Hypercalcemia in Patients With Neuroendocrine Neoplasms. Experience From Six Italian Referral Centers
BackgroundHypercalcemia is a common paraneoplastic syndrome which can occur in up to 10% of patients with advanced neoplasms. Paraneoplastic parathyroid hormone-related protein (PTHrP) represents the most frequent cause of this syndrome. In neuroendocrine neoplasms (NENs) paraneoplastic hypercalcemi...
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Frontiers Media S.A.
2021-05-01
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| Series: | Frontiers in Endocrinology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2021.665698/full |
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| author | Elisa Giannetta Franz Sesti Roberta Modica Erika Maria Grossrubatscher Valentina Guarnotta Alberto Ragni Isabella Zanata Annamaria Colao Antongiulio Faggiano |
| author_facet | Elisa Giannetta Franz Sesti Roberta Modica Erika Maria Grossrubatscher Valentina Guarnotta Alberto Ragni Isabella Zanata Annamaria Colao Antongiulio Faggiano |
| author_sort | Elisa Giannetta |
| collection | DOAJ |
| description | BackgroundHypercalcemia is a common paraneoplastic syndrome which can occur in up to 10% of patients with advanced neoplasms. Paraneoplastic parathyroid hormone-related protein (PTHrP) represents the most frequent cause of this syndrome. In neuroendocrine neoplasms (NENs) paraneoplastic hypercalcemia is rare.Case SeriesThe present series includes all patients with NENs and paraneoplastic hypercalcemia from four Italian centres: (I) A 40-year-old man was hospitalized for repeated episodes of falls, hyposthenia and drowsiness. Severe hypercalcemia was found. Metastatic pancreatic G2 NEN and PTHrP-related hypercalcemia were diagnosed. The patient started therapy with somatostatin analogs (SSA) and Denosumab. After disease progression peptide receptor radionuclide therapy (PRRT) was started with an objective response associated with PTHrP reduction and normocalcemia. (II) A 45-year-old man was referred for pancreatic G2 NEN. SSA and subsequently everolimus were administered for metastases occurrence. Hypercalcemia occurred and PRRT and Denosumab were started for disease progression with the onset of bone metastases. Despite disease stability after four cycles of PRRT the patient’s performance status worsened until death. (III) A 49-year-old woman was hospitalized for psychic slowdown, confusional state, sensory dullness. A severe hypercalcemia, associated with a pancreatic G1 NEN was diagnosed and treated with haemodialysis, bisphosphonates injections and continuous infusion of calcitonin. 1,25-dihydroxyvitamin D was high, PTHrP was undetectable. After surgery serum calcium levels and 1,25-dihydroxyvitamin D were normalized. (IV) A 69-year-old man was hospitalized after the onset of shortness of breath and dyspnea, asthenia and weight loss. Computed Tomography (CT) and 68Ga DOTATOC Positron Emission Tomography (PET)-CT revealed a left pulmonary nodule. Hypercalcemia and markedly elevated PTHrP levels were detected. The histological examination revealed an atypical carcinoid. After surgery, calcium levels were normalized, PTHrP was significantly reduced with an improvement of general conditions.ConclusionIn our series, paraneoplastic PTHrP-related hypercalcemia occurred in pancreatic NEN and in one bronchial carcinoid representing the third case in the literature. Our case associated with 1,25-dihydroxyvitamin D secretion represents the fourth case in the literature. PTHrP secretion should be considered in NENs’ patients with hypercalcemia. Acute treatment should be focused on lowering calcium levels, and long-term control can be achieved by tumor cytoreduction inhibiting PTHrP release. |
| first_indexed | 2024-12-21T19:43:58Z |
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| publishDate | 2021-05-01 |
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| series | Frontiers in Endocrinology |
| spelling | doaj.art-4b957e4a6f1a4396837c01b920850abf2022-12-21T18:52:23ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922021-05-011210.3389/fendo.2021.665698665698Case Report: Unmasking Hypercalcemia in Patients With Neuroendocrine Neoplasms. Experience From Six Italian Referral CentersElisa Giannetta0Franz Sesti1Roberta Modica2Erika Maria Grossrubatscher3Valentina Guarnotta4Alberto Ragni5Isabella Zanata6Annamaria Colao7Antongiulio Faggiano8Department of Experimental Medicine, “Sapienza” University of Rome, Rome, ItalyDepartment of Experimental Medicine, “Sapienza” University of Rome, Rome, ItalyDepartment of Clinical Medicine and Surgery, University “Federico II”, Naples, ItalyEndocrine Unit, ASST Grande Ospedale Metropolitano Niguarda, Milano, ItalyDept PROMISE, UOC Malattie Endocrine, del Ricambio e Della Nutrizione, University of Palermo, Palermo, ItalyOncological Endocrinology Unit, Department of Medical Sciences, Città della Salute e Della Scienza Hospital, University of Turin, Turin, ItalySection of Endocrinology and Internal Medicine, Department of Medical Sciences, University of Ferrara, Ferrara, ItalyDepartment of Clinical Medicine and Surgery, University “Federico II”, Naples, ItalyEndocrinology Unit, Department of Clinical and Molecular Medicine, Sant’Andrea Hospital, Sapienza University of Rome, Rome, ItalyBackgroundHypercalcemia is a common paraneoplastic syndrome which can occur in up to 10% of patients with advanced neoplasms. Paraneoplastic parathyroid hormone-related protein (PTHrP) represents the most frequent cause of this syndrome. In neuroendocrine neoplasms (NENs) paraneoplastic hypercalcemia is rare.Case SeriesThe present series includes all patients with NENs and paraneoplastic hypercalcemia from four Italian centres: (I) A 40-year-old man was hospitalized for repeated episodes of falls, hyposthenia and drowsiness. Severe hypercalcemia was found. Metastatic pancreatic G2 NEN and PTHrP-related hypercalcemia were diagnosed. The patient started therapy with somatostatin analogs (SSA) and Denosumab. After disease progression peptide receptor radionuclide therapy (PRRT) was started with an objective response associated with PTHrP reduction and normocalcemia. (II) A 45-year-old man was referred for pancreatic G2 NEN. SSA and subsequently everolimus were administered for metastases occurrence. Hypercalcemia occurred and PRRT and Denosumab were started for disease progression with the onset of bone metastases. Despite disease stability after four cycles of PRRT the patient’s performance status worsened until death. (III) A 49-year-old woman was hospitalized for psychic slowdown, confusional state, sensory dullness. A severe hypercalcemia, associated with a pancreatic G1 NEN was diagnosed and treated with haemodialysis, bisphosphonates injections and continuous infusion of calcitonin. 1,25-dihydroxyvitamin D was high, PTHrP was undetectable. After surgery serum calcium levels and 1,25-dihydroxyvitamin D were normalized. (IV) A 69-year-old man was hospitalized after the onset of shortness of breath and dyspnea, asthenia and weight loss. Computed Tomography (CT) and 68Ga DOTATOC Positron Emission Tomography (PET)-CT revealed a left pulmonary nodule. Hypercalcemia and markedly elevated PTHrP levels were detected. The histological examination revealed an atypical carcinoid. After surgery, calcium levels were normalized, PTHrP was significantly reduced with an improvement of general conditions.ConclusionIn our series, paraneoplastic PTHrP-related hypercalcemia occurred in pancreatic NEN and in one bronchial carcinoid representing the third case in the literature. Our case associated with 1,25-dihydroxyvitamin D secretion represents the fourth case in the literature. PTHrP secretion should be considered in NENs’ patients with hypercalcemia. Acute treatment should be focused on lowering calcium levels, and long-term control can be achieved by tumor cytoreduction inhibiting PTHrP release.https://www.frontiersin.org/articles/10.3389/fendo.2021.665698/fullparaneoplastic hypercalcemiaparathyroid hormone-related proteinpancreatic NENbronchial carcinoid1,25-dihydroxyvitamin D |
| spellingShingle | Elisa Giannetta Franz Sesti Roberta Modica Erika Maria Grossrubatscher Valentina Guarnotta Alberto Ragni Isabella Zanata Annamaria Colao Antongiulio Faggiano Case Report: Unmasking Hypercalcemia in Patients With Neuroendocrine Neoplasms. Experience From Six Italian Referral Centers Frontiers in Endocrinology paraneoplastic hypercalcemia parathyroid hormone-related protein pancreatic NEN bronchial carcinoid 1,25-dihydroxyvitamin D |
| title | Case Report: Unmasking Hypercalcemia in Patients With Neuroendocrine Neoplasms. Experience From Six Italian Referral Centers |
| title_full | Case Report: Unmasking Hypercalcemia in Patients With Neuroendocrine Neoplasms. Experience From Six Italian Referral Centers |
| title_fullStr | Case Report: Unmasking Hypercalcemia in Patients With Neuroendocrine Neoplasms. Experience From Six Italian Referral Centers |
| title_full_unstemmed | Case Report: Unmasking Hypercalcemia in Patients With Neuroendocrine Neoplasms. Experience From Six Italian Referral Centers |
| title_short | Case Report: Unmasking Hypercalcemia in Patients With Neuroendocrine Neoplasms. Experience From Six Italian Referral Centers |
| title_sort | case report unmasking hypercalcemia in patients with neuroendocrine neoplasms experience from six italian referral centers |
| topic | paraneoplastic hypercalcemia parathyroid hormone-related protein pancreatic NEN bronchial carcinoid 1,25-dihydroxyvitamin D |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2021.665698/full |
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