Cargando…
PSAT190 Denosumab use for life-threatening hypercalcemia of malignancy in a toddler. A weight base dose
INTRODUCTION: Denosumab, an inhibitor of receptor activator of nuclear factor kappa-B ligand, has emerged as an important novel therapy for osteoporosis, hypercalcemia of malignancy (HCM), and other skeletal disorders in adults. While off-label use has been reported in children with these conditions...
Autores principales: | , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9624898/ http://dx.doi.org/10.1210/jendso/bvac150.423 |
_version_ | 1784822350105018368 |
---|---|
author | Castano, Gabriel Alarcon-Mantilla, Guido Bhar, Saleh Bansal, Nidhi |
author_facet | Castano, Gabriel Alarcon-Mantilla, Guido Bhar, Saleh Bansal, Nidhi |
author_sort | Castano, Gabriel |
collection | PubMed |
description | INTRODUCTION: Denosumab, an inhibitor of receptor activator of nuclear factor kappa-B ligand, has emerged as an important novel therapy for osteoporosis, hypercalcemia of malignancy (HCM), and other skeletal disorders in adults. While off-label use has been reported in children with these conditions, pediatric data is limited. We report a case of a 35-month old patient who had received Denosumab for management of life-threatening HCM. CASE: 2-year-old male previously healthy who presented with increase work of breathing, altered mental status, and changes in his voice in the setting of progressive neck swelling over 2-weeks. Initial workup revealed a large mediastinal mass and metabolic anomalies including hypercalcemia (21.6mg/dL), shortened QTc on ECG, and acute kidney injury (AKI) stage 1-2 (eGFR 71 ml/min/1.73m2). Flow cytometry confirmed diagnosis of T-Cell ALL. PTHrP was 8.6pmol/L with a PTH of 7.1Pg/ml and a 25OH vitamin D of 38.9Ng/ml with 1,25OH of 6pg/ml. On admission, patient started maintenance IV fluids, dexamethasone, calcitonin, and denosumab 0.3mg/kg. His calcium normalized by day 2-3 of treatment and eventually started oral calcium supplementation (25mg/kg elemental) with calcitriol to prevent hypocalcemia. Calcium stabilized with the lowest level at 7.6mg/dL on day 7; did not require IV calcium correction during hospitalization and renal function normalized. Patient was discharged on 0.5 mcg of calcitriol daily and 125mg/kg/day of elemental calcium. DISCUSSION: HCM develops in less than 1% of pediatric patients with cancer. Most cases are due to systemic parathyroid hormone-related protein, followed by osteolytic metastases leading to inflammatory cytokines locally released and least common via ectopic production of 1,25 dihydroxy vitamin D. HCM is an oncologic emergency. In adults, Denosumab has been used for HCM as a second-line agent after failure to respond to bisphosphonates, or when they are contraindicated. Bisphosphonates have shown to worsen renal function, even in those with normal glomerular filtration. Denosumab has been overall very well tolerated by patients. Initial hypocalcemia that peaks between days 4–10, and rebound hypercalcemia are one of the more feared side effects. Despite Denosumab not been cleared by the kidney, in adult patients with AKI or CKD, they have a higher risk of developing rebound hypercalcemia after receiving the standard 120mg SQ dose; a weight base dose was proposed, 0.3mg/kg for those with renal impairment. The reported dose in pediatrics for HCM has been 120mg, but we decided to do a weight base dose as our patient had AKI at presentation, with increased risk for decompensation once chemotherapy was started. Our patient responded very well to Denosumab with improvement in hypercalcemia, without severe hypocalcemia requiring IV calcium supplementation. Incidentally, to the best of our knowledge, our patient is the youngest patient reported to have received Denosumab for management of HCM. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m. |
format | Online Article Text |
id | pubmed-9624898 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-96248982022-11-14 PSAT190 Denosumab use for life-threatening hypercalcemia of malignancy in a toddler. A weight base dose Castano, Gabriel Alarcon-Mantilla, Guido Bhar, Saleh Bansal, Nidhi J Endocr Soc Bone & Mineral Metabolism INTRODUCTION: Denosumab, an inhibitor of receptor activator of nuclear factor kappa-B ligand, has emerged as an important novel therapy for osteoporosis, hypercalcemia of malignancy (HCM), and other skeletal disorders in adults. While off-label use has been reported in children with these conditions, pediatric data is limited. We report a case of a 35-month old patient who had received Denosumab for management of life-threatening HCM. CASE: 2-year-old male previously healthy who presented with increase work of breathing, altered mental status, and changes in his voice in the setting of progressive neck swelling over 2-weeks. Initial workup revealed a large mediastinal mass and metabolic anomalies including hypercalcemia (21.6mg/dL), shortened QTc on ECG, and acute kidney injury (AKI) stage 1-2 (eGFR 71 ml/min/1.73m2). Flow cytometry confirmed diagnosis of T-Cell ALL. PTHrP was 8.6pmol/L with a PTH of 7.1Pg/ml and a 25OH vitamin D of 38.9Ng/ml with 1,25OH of 6pg/ml. On admission, patient started maintenance IV fluids, dexamethasone, calcitonin, and denosumab 0.3mg/kg. His calcium normalized by day 2-3 of treatment and eventually started oral calcium supplementation (25mg/kg elemental) with calcitriol to prevent hypocalcemia. Calcium stabilized with the lowest level at 7.6mg/dL on day 7; did not require IV calcium correction during hospitalization and renal function normalized. Patient was discharged on 0.5 mcg of calcitriol daily and 125mg/kg/day of elemental calcium. DISCUSSION: HCM develops in less than 1% of pediatric patients with cancer. Most cases are due to systemic parathyroid hormone-related protein, followed by osteolytic metastases leading to inflammatory cytokines locally released and least common via ectopic production of 1,25 dihydroxy vitamin D. HCM is an oncologic emergency. In adults, Denosumab has been used for HCM as a second-line agent after failure to respond to bisphosphonates, or when they are contraindicated. Bisphosphonates have shown to worsen renal function, even in those with normal glomerular filtration. Denosumab has been overall very well tolerated by patients. Initial hypocalcemia that peaks between days 4–10, and rebound hypercalcemia are one of the more feared side effects. Despite Denosumab not been cleared by the kidney, in adult patients with AKI or CKD, they have a higher risk of developing rebound hypercalcemia after receiving the standard 120mg SQ dose; a weight base dose was proposed, 0.3mg/kg for those with renal impairment. The reported dose in pediatrics for HCM has been 120mg, but we decided to do a weight base dose as our patient had AKI at presentation, with increased risk for decompensation once chemotherapy was started. Our patient responded very well to Denosumab with improvement in hypercalcemia, without severe hypocalcemia requiring IV calcium supplementation. Incidentally, to the best of our knowledge, our patient is the youngest patient reported to have received Denosumab for management of HCM. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m. Oxford University Press 2022-11-01 /pmc/articles/PMC9624898/ http://dx.doi.org/10.1210/jendso/bvac150.423 Text en © The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (https://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Bone & Mineral Metabolism Castano, Gabriel Alarcon-Mantilla, Guido Bhar, Saleh Bansal, Nidhi PSAT190 Denosumab use for life-threatening hypercalcemia of malignancy in a toddler. A weight base dose |
title | PSAT190 Denosumab use for life-threatening hypercalcemia of malignancy in a toddler. A weight base dose |
title_full | PSAT190 Denosumab use for life-threatening hypercalcemia of malignancy in a toddler. A weight base dose |
title_fullStr | PSAT190 Denosumab use for life-threatening hypercalcemia of malignancy in a toddler. A weight base dose |
title_full_unstemmed | PSAT190 Denosumab use for life-threatening hypercalcemia of malignancy in a toddler. A weight base dose |
title_short | PSAT190 Denosumab use for life-threatening hypercalcemia of malignancy in a toddler. A weight base dose |
title_sort | psat190 denosumab use for life-threatening hypercalcemia of malignancy in a toddler. a weight base dose |
topic | Bone & Mineral Metabolism |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9624898/ http://dx.doi.org/10.1210/jendso/bvac150.423 |
work_keys_str_mv | AT castanogabriel psat190denosumabuseforlifethreateninghypercalcemiaofmalignancyinatoddleraweightbasedose AT alarconmantillaguido psat190denosumabuseforlifethreateninghypercalcemiaofmalignancyinatoddleraweightbasedose AT bharsaleh psat190denosumabuseforlifethreateninghypercalcemiaofmalignancyinatoddleraweightbasedose AT bansalnidhi psat190denosumabuseforlifethreateninghypercalcemiaofmalignancyinatoddleraweightbasedose |