Under physiological conditions, serum calcium concentration is tightly regulated. Abnormalities of parathyroid function, bone resorption, renal calcium reabsorption or dihydroxylation of vitamin D may cause regulatory mechanisms to fail and serum calcium to rise. Serum calcium is bound to albumin, and measurements should be adjusted for serum albumin. This guideline aims to take the non-specialist through the initial phase of assessment and management

Jennifer Walsh

Neil Gittoes

Peter Selby

Society for Endocrinology Clinical Committee

Endocrine Connections

PubMed

Walsh, Jennifer

Gittoes, Neil

Selby, Peter

University of Birmingham Research Portal

  University of BirminghamEmergency management of acute hypercalcaemia inadult patientsWalsh, Jennifer; Gittoes, Neil; Selby, PeterDOI:10.1530/EC-16-0055License:Creative Commons: Attribution-NonCommercial-NoDerivs (CC BY-NC-ND)Document VersionPublisher's PDF, also known as Version of recordCitation for published version (Harvard):Walsh, J, Gittoes, N & Selby, P 2016, 'Emergency management of acute hypercalcaemia in adult patients',Endocrine Connections, vol. 5, pp. G9-G11. https://doi.org/10.1530/EC-16-0055Link to publication on Research at Birmingham portalGeneral rightsUnless a licence is specified above, all rights (including copyright and moral rights) in this document are retained by the authors and/or thecopyright holders. The express permission of the copyright holder must be obtained for any use of this material other than for purposespermitted by law.•Users may freely distribute the URL that is used to identify this publication.•Users may download and/or print one copy of the publication from the University of Birmingham research portal for the purpose of privatestudy or non-commercial research.•User may use extracts from the document in line with the concept of ‘fair dealing’ under the Copyright, Designs and Patents Act 1988 (?)•Users may not further distribute the material nor use it for the purposes of commercial gain.Where a licence is displayed above, please note the terms and conditions of the licence govern your use of this document.When citing, please reference the published version.Take down policyWhile the University of Birmingham exercises care and attention in making items available there are rare occasions when an item has beenuploaded in error or has been deemed to be commercially or otherwise sensitive.If you believe that this is the case for this document, please contact UBIRA@lists.bham.ac.uk providing details and we will remove access tothe work immediately and investigate.Download date: 26. Dec. 2025DOI: 10.1530/EC-16-0055http://www.endocrineconnections.org © 2016 Society for EndocrinologyPublished by Bioscientifica LtdThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.Acute hypercalcaemia emergency guidanceJ Walsh et al.Emergency GuidanceOpen Access53Endocrine ConnectionsG9–G11 G9:5Correspondence  should be addressed  to J Walsh  Email  j.walsh@sheffield.ac.ukSOCIETY FOR ENDOCRINOLOGY  ENDOCRINE EMERGENCY GUIDANCEEmergency management of acute hypercalcaemia in adult patientsJennifer Walsh1, Neil Gittoes2, Peter Selby3 and the Society for Endocrinology  Clinical Committee41The Mellanby Centre for Bone Research, The Medical School, The University of Sheffield, Sheffield, UK2Centre for Endocrinology, Diabetes and Metabolism, University Hospitals Birmingham & University of Birmingham, Birmingham Health Partners, Birmingham, UK3Department of Medicine, Manchester Royal Infirmary, Manchester, UK4The Society for Endocrinology, 22 Apex Court, Woodlands, Bradley Stoke, Bristol, UK10.1530/EC-16-0055IntroductionUnder physiological conditions, serum calcium concentration is tightly regulated. Abnormalities of parathyroid function, bone resorption, renal calcium reabsorption or dihydroxylation of vitamin D may cause regulatory mechanisms to fail and serum calcium to rise. Serum calcium is bound to albumin, and measurements should be adjusted for serum albumin. This guideline aims to take the non-specialist through the initial phase of assessment and management.Severity of hypercalcaemia • Shortened QT interval and dysrhythmias • Nephrolithiasis, nephrocalcinosis • Pancreatitis • Peptic ulceration • Hypertension, cardiomyopathy • Muscle weakness • Band keratopathyCauses<3.0 mmol/L: often asymptomatic and does not usually require urgent correction3.0–3.5 mmol/L: may be well tolerated if it has risen slowly, but may be symptomatic and prompt treatment is usually indicated>3.5 mmol/L: requires urgent correction due to the risk of dysrhythmia and comaClinical features of hypercalcaemia • Polyuria and thirst • Anorexia, nausea and constipation • Mood disturbance, cognitive dysfunction, confusion and coma • Renal impairmentNinety percent of hypercalcaemia is due to primary hyperparathyroidism or malignancyLess common causes include • Thiazide diuretics • Familial hypocalciuric hypercalcaemia • Non-malignant granulomatous disease • Thyrotoxicosis • Tertiary hyperparathyroidism • Hypervitaminosis D • Rhabdomyolysis • Lithium • Immobilisation • Adrenal insufficiency • Milk-alkali syndrome • Hypervitaminosis A • Theophylline toxicity • PhaeochromocytomaDOI: 10.1530/EC-16-0055http://www.endocrineconnections.org © 2016 Society for EndocrinologyPublished by Bioscientifica LtdThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.Emergency Guidance J Walsh et al. Acute hypercalcaemia emergency guidanceG10–G11 5:G10Endocrine ConnectionsInvestigationHistory – Symptoms of hypercalcaemia and duration – Symptoms of underlying causes, e.g. weight loss, night sweats, cough – Family history – Drugs including supplements and over-the-counter preparationsExamination – Assess for cognitive impairment – Fluid balance status – For underlying causes, including neck, respiratory, abdomen, breasts, lymph nodesECG – Look for shortened QT interval or other conduction abnormalitiesBloods – Calcium adjusted for albumin – Phosphate – PTH – Urea and electrolytesHigh calcium and high PTH = primary or tertiary hyperparathyroidism*High calcium and low PTH = malignancy or other less common causes(*Familial hypocalciuric hypercalcaemia may be misdiagnosed as primary hyperparathyroidism due to hypercalcaemia with inappropriately normal or raised PTH. However, the hypercalcaemia is not usually severe and it is less likely to present as an emergency)If further treatment required after intravenous  saline, consider intravenous bisphosphonatesManagementRehydrationIntravenous 0.9% saline 4–6 L in 24 h – Monitor for fluid overload if renal impairment or elderly – Loop diuretics rarely used and only if fluid overload develops; not effective for reducing serum calcium – May need to consider dialysis if severe renal failureZoledronic acid 4 mg over 15 minOR  Pamidronate 30–90 mg (depending on severity of hypercalcaemia) at 20 mg/hOR Ibandronic acid 2–4 mg – Give more slowly and consider dose reduction in renal impairment – Monitor serum calcium response: will reach nadir at 2–4 days – Can cause hypocalcaemia if vitamin D deficiency or suppressed PTHSecond-line treatmentsGlucocorticoids (inhibit 1,25OHD production) – In lymphoma, other granulomatous diseases or 25OHD poisoning – Prednisolone 40 mg daily – Usually effective in 2–4 daysCalcimimetics, denosumab, calcitonin – Under specialist supervision – Can be considered if poor response to other  measuresParathyroidectomy – Can be considered in acute presentation of primary hyperparathyroidism if severe hypercalcaemia and poor response to other measuresDisclaimerThe document should be considered as a guideline only; it is not intended to determine an absolute standard of medical care. The doctors concerned must make the management plan for an individual patient.Sources 1 LeGrand SB, Leskuski D & Zama I. Narrative review: furosemide for hypercalcemia: an unproven yet common practice. Annals of Internal Medicine 2008 149 259–263. (doi:10.7326/0003-4819-149-4-200808190-00007) 2 Nussbaum SR, Younger J, Vandepol CJ, Gagel RF, Zuber MA, Chapman R, Henderson IC & Malette IE. Single-dose intravenous therapy for the treatment of hypercalcaemia of malignancy: DOI: 10.1530/EC-16-0055http://www.endocrineconnections.org © 2016 Society for EndocrinologyPublished by Bioscientifica LtdThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.Emergency Guidance J Walsh et al. Acute hypercalcaemia emergency guidanceEndocrine ConnectionsG11–G11 5:G11Endocrine Connectionscomparison of 30-, 60-, and 90mg doses. American Journal of Medicine 1993 95 297–304. (doi:10.1016/0002-9343(93)90282-T) 3 Major P, Lortholary A, Hon J, Abdi E, Mills G, Menssen HD,  Yunus F, Bell R, Body J, Quebe-Fehling E, et al. Zoledronic acid is superior to pamidronate in the treatment of hypercalcemia of malignancy: a pooled analysis of two randomized, controlled clinical trials. Journal of Clinical Oncology 2001 19 558–567. 4 Wineski LA. Salmon calcitonin in the management of hypercalcaemia. Calcified Tissue International 1990 46 (Supplement) S26–S30. 5 Marcocci C, Chanson P, Shoback D, Bilezikian J, Fernandez-Cruz L, Orgiazzi J, Henzen C, Cheng S, Sterling LR, Lu J, et al. Cinacalcet reduces serum calcium concentrations in patients with intractable primary hyperparathyroidism. Journal of Clinical Endocrinology and Metabolism 2009 94 2766–2772. (doi:10.1210/jc.2008-2640) 6 Rostoker G, Bellamy J & Janklewicz P. Cinacalcet to prevent parathyrotoxic crises in hypercalcaemic patients awaiting parathyroidectomy. BMJ Case Reports 2011 2011 bcr1220103663. (doi:10.1136/bcr.12.2010.3663) Received in final form 3 August 2016Accepted 3 August 2016

English

Emergency management of acute hypercalcaemia in adult patients

Walsh, J.

Gittoes, N.

Selby, P.

White Rose Research Online

SOCIETY FOR ENDOCRINOLOGY ENDOCRINE EMERGENCY GUIDANCE: Emergency management of acute hypercalcaemia in adult patients

  Emergency management of acute hypercalcaemia inadult patientsWalsh, Jennifer; Gittoes, Neil; Selby, PeterDOI:10.1530/EC-16-0055License:Creative Commons: Attribution-NonCommercial-NoDerivs (CC BY-NC-ND)Document VersionPublisher's PDF, also known as Version of recordCitation for published version (Harvard):Walsh, J, Gittoes, N & Selby, P 2016, 'Emergency management of acute hypercalcaemia in adult patients',Endocrine Connections, vol. 5, pp. G9-G11. https://doi.org/10.1530/EC-16-0055Link to publication on Research at Birmingham portalGeneral rightsUnless a licence is specified above, all rights (including copyright and moral rights) in this document are retained by the authors and/or thecopyright holders. The express permission of the copyright holder must be obtained for any use of this material other than for purposespermitted by law.•	Users may freely distribute the URL that is used to identify this publication.•	Users may download and/or print one copy of the publication from the University of Birmingham research portal for the purpose of privatestudy or non-commercial research.•	User may use extracts from the document in line with the concept of ‘fair dealing’ under the Copyright, Designs and Patents Act 1988 (?)•	Users may not further distribute the material nor use it for the purposes of commercial gain.Where a licence is displayed above, please note the terms and conditions of the licence govern your use of this document.When citing, please reference the published version.Take down policyWhile the University of Birmingham exercises care and attention in making items available there are rare occasions when an item has beenuploaded in error or has been deemed to be commercially or otherwise sensitive.If you believe that this is the case for this document, please contact UBIRA@lists.bham.ac.uk providing details and we will remove access tothe work immediately and investigate.Download date: 01. Feb. 2019DOI: 10.1530/EC-16-0055http://www.endocrineconnections.org © 2016 Society for EndocrinologyPublished by Bioscientifica LtdThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.Acute hypercalcaemia emergency guidanceJ Walsh et al.Emergency GuidanceOpen Access53Endocrine ConnectionsG9–G11 G9:5Correspondence  should be addressed  to J Walsh  Email  j.walsh@sheffield.ac.ukSOCIETY FOR ENDOCRINOLOGY  ENDOCRINE EMERGENCY GUIDANCEEmergency management of acute hypercalcaemia in adult patientsJennifer Walsh1, Neil Gittoes2, Peter Selby3 and the Society for Endocrinology  Clinical Committee41The Mellanby Centre for Bone Research, The Medical School, The University of Sheffield, Sheffield, UK2Centre for Endocrinology, Diabetes and Metabolism, University Hospitals Birmingham & University of Birmingham, Birmingham Health Partners, Birmingham, UK3Department of Medicine, Manchester Royal Infirmary, Manchester, UK4The Society for Endocrinology, 22 Apex Court, Woodlands, Bradley Stoke, Bristol, UK10.1530/EC-16-0055IntroductionUnder physiological conditions, serum calcium concentration is tightly regulated. Abnormalities of parathyroid function, bone resorption, renal calcium reabsorption or dihydroxylation of vitamin D may cause regulatory mechanisms to fail and serum calcium to rise. Serum calcium is bound to albumin, and measurements should be adjusted for serum albumin. This guideline aims to take the non-specialist through the initial phase of assessment and management.Severity of hypercalcaemia • Shortened QT interval and dysrhythmias • Nephrolithiasis, nephrocalcinosis • Pancreatitis • Peptic ulceration • Hypertension, cardiomyopathy • Muscle weakness • Band keratopathyCauses<3.0 mmol/L: often asymptomatic and does not usually require urgent correction3.0–3.5 mmol/L: may be well tolerated if it has risen slowly, but may be symptomatic and prompt treatment is usually indicated>3.5 mmol/L: requires urgent correction due to the risk of dysrhythmia and comaClinical features of hypercalcaemia • Polyuria and thirst • Anorexia, nausea and constipation • Mood disturbance, cognitive dysfunction, confusion and coma • Renal impairmentNinety percent of hypercalcaemia is due to primary hyperparathyroidism or malignancyLess common causes include • Thiazide diuretics • Familial hypocalciuric hypercalcaemia • Non-malignant granulomatous disease • Thyrotoxicosis • Tertiary hyperparathyroidism • Hypervitaminosis D • Rhabdomyolysis • Lithium • Immobilisation • Adrenal insufficiency • Milk-alkali syndrome • Hypervitaminosis A • Theophylline toxicity • PhaeochromocytomaDOI: 10.1530/EC-16-0055http://www.endocrineconnections.org © 2016 Society for EndocrinologyPublished by Bioscientifica LtdThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.Emergency Guidance J Walsh et al. Acute hypercalcaemia emergency guidanceG10–G11 5:G10Endocrine ConnectionsInvestigationHistory – Symptoms of hypercalcaemia and duration – Symptoms of underlying causes, e.g. weight loss, night sweats, cough – Family history – Drugs including supplements and over-the-counter preparationsExamination – Assess for cognitive impairment – Fluid balance status – For underlying causes, including neck, respiratory, abdomen, breasts, lymph nodesECG – Look for shortened QT interval or other conduction abnormalitiesBloods – Calcium adjusted for albumin – Phosphate – PTH – Urea and electrolytesHigh calcium and high PTH = primary or tertiary hyperparathyroidism*High calcium and low PTH = malignancy or other less common causes(*Familial hypocalciuric hypercalcaemia may be misdiagnosed as primary hyperparathyroidism due to hypercalcaemia with inappropriately normal or raised PTH. However, the hypercalcaemia is not usually severe and it is less likely to present as an emergency)If further treatment required after intravenous  saline, consider intravenous bisphosphonatesManagementRehydrationIntravenous 0.9% saline 4–6 L in 24 h – Monitor for fluid overload if renal impairment or elderly – Loop diuretics rarely used and only if fluid overload develops; not effective for reducing serum calcium – May need to consider dialysis if severe renal failureZoledronic acid 4 mg over 15 minOR  Pamidronate 30–90 mg (depending on severity of hypercalcaemia) at 20 mg/hOR Ibandronic acid 2–4 mg – Give more slowly and consider dose reduction in renal impairment – Monitor serum calcium response: will reach nadir at 2–4 days – Can cause hypocalcaemia if vitamin D deficiency or suppressed PTHSecond-line treatmentsGlucocorticoids (inhibit 1,25OHD production) – In lymphoma, other granulomatous diseases or 25OHD poisoning – Prednisolone 40 mg daily – Usually effective in 2–4 daysCalcimimetics, denosumab, calcitonin – Under specialist supervision – Can be considered if poor response to other  measuresParathyroidectomy – Can be considered in acute presentation of primary hyperparathyroidism if severe hypercalcaemia and poor response to other measuresDisclaimerThe document should be considered as a guideline only; it is not intended to determine an absolute standard of medical care. The doctors concerned must make the management plan for an individual patient.Sources 1 LeGrand SB, Leskuski D & Zama I. Narrative review: furosemide for hypercalcemia: an unproven yet common practice. Annals of Internal Medicine 2008 149 259–263. (doi:10.7326/0003-4819-149-4-200808190-00007) 2 Nussbaum SR, Younger J, Vandepol CJ, Gagel RF, Zuber MA, Chapman R, Henderson IC & Malette IE. Single-dose intravenous therapy for the treatment of hypercalcaemia of malignancy: DOI: 10.1530/EC-16-0055http://www.endocrineconnections.org © 2016 Society for EndocrinologyPublished by Bioscientifica LtdThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.Emergency Guidance J Walsh et al. Acute hypercalcaemia emergency guidanceEndocrine ConnectionsG11–G11 5:G11Endocrine Connectionscomparison of 30-, 60-, and 90mg doses. American Journal of Medicine 1993 95 297–304. (doi:10.1016/0002-9343(93)90282-T) 3 Major P, Lortholary A, Hon J, Abdi E, Mills G, Menssen HD,  Yunus F, Bell R, Body J, Quebe-Fehling E, et al. Zoledronic acid is superior to pamidronate in the treatment of hypercalcemia of malignancy: a pooled analysis of two randomized, controlled clinical trials. Journal of Clinical Oncology 2001 19 558–567. 4 Wineski LA. Salmon calcitonin in the management of hypercalcaemia. Calcified Tissue International 1990 46 (Supplement) S26–S30. 5 Marcocci C, Chanson P, Shoback D, Bilezikian J, Fernandez-Cruz L, Orgiazzi J, Henzen C, Cheng S, Sterling LR, Lu J, et al. Cinacalcet reduces serum calcium concentrations in patients with intractable primary hyperparathyroidism. Journal of Clinical Endocrinology and Metabolism 2009 94 2766–2772. (doi:10.1210/jc.2008-2640) 6 Rostoker G, Bellamy J & Janklewicz P. Cinacalcet to prevent parathyrotoxic crises in hypercalcaemic patients awaiting parathyroidectomy. BMJ Case Reports 2011 2011 bcr1220103663. (doi:10.1136/bcr.12.2010.3663) Received in final form 3 August 2016Accepted 3 August 2016

  University of BirminghamEmergency management of acute hypercalcaemia inadult patientsWalsh, Jennifer; Gittoes, Neil; Selby, PeterDOI:10.1530/EC-16-0055License:Creative Commons: Attribution-NonCommercial-NoDerivs (CC BY-NC-ND)Document VersionPublisher's PDF, also known as Version of recordCitation for published version (Harvard):Walsh, J, Gittoes, N & Selby, P 2016, 'Emergency management of acute hypercalcaemia in adult patients',Endocrine Connections, vol. 5, pp. G9-G11. https://doi.org/10.1530/EC-16-0055Link to publication on Research at Birmingham portalGeneral rightsUnless a licence is specified above, all rights (including copyright and moral rights) in this document are retained by the authors and/or thecopyright holders. The express permission of the copyright holder must be obtained for any use of this material other than for purposespermitted by law.•	Users may freely distribute the URL that is used to identify this publication.•	Users may download and/or print one copy of the publication from the University of Birmingham research portal for the purpose of privatestudy or non-commercial research.•	User may use extracts from the document in line with the concept of ‘fair dealing’ under the Copyright, Designs and Patents Act 1988 (?)•	Users may not further distribute the material nor use it for the purposes of commercial gain.Where a licence is displayed above, please note the terms and conditions of the licence govern your use of this document.When citing, please reference the published version.Take down policyWhile the University of Birmingham exercises care and attention in making items available there are rare occasions when an item has beenuploaded in error or has been deemed to be commercially or otherwise sensitive.If you believe that this is the case for this document, please contact UBIRA@lists.bham.ac.uk providing details and we will remove access tothe work immediately and investigate.Download date: 01. Mar. 2020DOI: 10.1530/EC-16-0055http://www.endocrineconnections.org © 2016 Society for EndocrinologyPublished by Bioscientifica LtdThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.Acute hypercalcaemia emergency guidanceJ Walsh et al.Emergency GuidanceOpen Access53Endocrine ConnectionsG9–G11 G9:5Correspondence  should be addressed  to J Walsh  Email  j.walsh@sheffield.ac.ukSOCIETY FOR ENDOCRINOLOGY  ENDOCRINE EMERGENCY GUIDANCEEmergency management of acute hypercalcaemia in adult patientsJennifer Walsh1, Neil Gittoes2, Peter Selby3 and the Society for Endocrinology  Clinical Committee41The Mellanby Centre for Bone Research, The Medical School, The University of Sheffield, Sheffield, UK2Centre for Endocrinology, Diabetes and Metabolism, University Hospitals Birmingham & University of Birmingham, Birmingham Health Partners, Birmingham, UK3Department of Medicine, Manchester Royal Infirmary, Manchester, UK4The Society for Endocrinology, 22 Apex Court, Woodlands, Bradley Stoke, Bristol, UK10.1530/EC-16-0055IntroductionUnder physiological conditions, serum calcium concentration is tightly regulated. Abnormalities of parathyroid function, bone resorption, renal calcium reabsorption or dihydroxylation of vitamin D may cause regulatory mechanisms to fail and serum calcium to rise. Serum calcium is bound to albumin, and measurements should be adjusted for serum albumin. This guideline aims to take the non-specialist through the initial phase of assessment and management.Severity of hypercalcaemia • Shortened QT interval and dysrhythmias • Nephrolithiasis, nephrocalcinosis • Pancreatitis • Peptic ulceration • Hypertension, cardiomyopathy • Muscle weakness • Band keratopathyCauses<3.0 mmol/L: often asymptomatic and does not usually require urgent correction3.0–3.5 mmol/L: may be well tolerated if it has risen slowly, but may be symptomatic and prompt treatment is usually indicated>3.5 mmol/L: requires urgent correction due to the risk of dysrhythmia and comaClinical features of hypercalcaemia • Polyuria and thirst • Anorexia, nausea and constipation • Mood disturbance, cognitive dysfunction, confusion and coma • Renal impairmentNinety percent of hypercalcaemia is due to primary hyperparathyroidism or malignancyLess common causes include • Thiazide diuretics • Familial hypocalciuric hypercalcaemia • Non-malignant granulomatous disease • Thyrotoxicosis • Tertiary hyperparathyroidism • Hypervitaminosis D • Rhabdomyolysis • Lithium • Immobilisation • Adrenal insufficiency • Milk-alkali syndrome • Hypervitaminosis A • Theophylline toxicity • PhaeochromocytomaDOI: 10.1530/EC-16-0055http://www.endocrineconnections.org © 2016 Society for EndocrinologyPublished by Bioscientifica LtdThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.Emergency Guidance J Walsh et al. Acute hypercalcaemia emergency guidanceG10–G11 5:G10Endocrine ConnectionsInvestigationHistory – Symptoms of hypercalcaemia and duration – Symptoms of underlying causes, e.g. weight loss, night sweats, cough – Family history – Drugs including supplements and over-the-counter preparationsExamination – Assess for cognitive impairment – Fluid balance status – For underlying causes, including neck, respiratory, abdomen, breasts, lymph nodesECG – Look for shortened QT interval or other conduction abnormalitiesBloods – Calcium adjusted for albumin – Phosphate – PTH – Urea and electrolytesHigh calcium and high PTH = primary or tertiary hyperparathyroidism*High calcium and low PTH = malignancy or other less common causes(*Familial hypocalciuric hypercalcaemia may be misdiagnosed as primary hyperparathyroidism due to hypercalcaemia with inappropriately normal or raised PTH. However, the hypercalcaemia is not usually severe and it is less likely to present as an emergency)If further treatment required after intravenous  saline, consider intravenous bisphosphonatesManagementRehydrationIntravenous 0.9% saline 4–6 L in 24 h – Monitor for fluid overload if renal impairment or elderly – Loop diuretics rarely used and only if fluid overload develops; not effective for reducing serum calcium – May need to consider dialysis if severe renal failureZoledronic acid 4 mg over 15 minOR  Pamidronate 30–90 mg (depending on severity of hypercalcaemia) at 20 mg/hOR Ibandronic acid 2–4 mg – Give more slowly and consider dose reduction in renal impairment – Monitor serum calcium response: will reach nadir at 2–4 days – Can cause hypocalcaemia if vitamin D deficiency or suppressed PTHSecond-line treatmentsGlucocorticoids (inhibit 1,25OHD production) – In lymphoma, other granulomatous diseases or 25OHD poisoning – Prednisolone 40 mg daily – Usually effective in 2–4 daysCalcimimetics, denosumab, calcitonin – Under specialist supervision – Can be considered if poor response to other  measuresParathyroidectomy – Can be considered in acute presentation of primary hyperparathyroidism if severe hypercalcaemia and poor response to other measuresDisclaimerThe document should be considered as a guideline only; it is not intended to determine an absolute standard of medical care. The doctors concerned must make the management plan for an individual patient.Sources 1 LeGrand SB, Leskuski D & Zama I. Narrative review: furosemide for hypercalcemia: an unproven yet common practice. Annals of Internal Medicine 2008 149 259–263. (doi:10.7326/0003-4819-149-4-200808190-00007) 2 Nussbaum SR, Younger J, Vandepol CJ, Gagel RF, Zuber MA, Chapman R, Henderson IC & Malette IE. Single-dose intravenous therapy for the treatment of hypercalcaemia of malignancy: DOI: 10.1530/EC-16-0055http://www.endocrineconnections.org © 2016 Society for EndocrinologyPublished by Bioscientifica LtdThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.Emergency Guidance J Walsh et al. Acute hypercalcaemia emergency guidanceEndocrine ConnectionsG11–G11 5:G11Endocrine Connectionscomparison of 30-, 60-, and 90mg doses. American Journal of Medicine 1993 95 297–304. (doi:10.1016/0002-9343(93)90282-T) 3 Major P, Lortholary A, Hon J, Abdi E, Mills G, Menssen HD,  Yunus F, Bell R, Body J, Quebe-Fehling E, et al. Zoledronic acid is superior to pamidronate in the treatment of hypercalcemia of malignancy: a pooled analysis of two randomized, controlled clinical trials. Journal of Clinical Oncology 2001 19 558–567. 4 Wineski LA. Salmon calcitonin in the management of hypercalcaemia. Calcified Tissue International 1990 46 (Supplement) S26–S30. 5 Marcocci C, Chanson P, Shoback D, Bilezikian J, Fernandez-Cruz L, Orgiazzi J, Henzen C, Cheng S, Sterling LR, Lu J, et al. Cinacalcet reduces serum calcium concentrations in patients with intractable primary hyperparathyroidism. Journal of Clinical Endocrinology and Metabolism 2009 94 2766–2772. (doi:10.1210/jc.2008-2640) 6 Rostoker G, Bellamy J & Janklewicz P. Cinacalcet to prevent parathyrotoxic crises in hypercalcaemic patients awaiting parathyroidectomy. BMJ Case Reports 2011 2011 bcr1220103663. (doi:10.1136/bcr.12.2010.3663) Received in final form 3 August 2016Accepted 3 August 2016

DOI: 10.1530/EC-16-0055http://www.endocrineconnections.org © 2016 Society for EndocrinologyPublished by Bioscientifica LtdThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.Acute hypercalcaemia emergency guidanceJ Walsh et al.Emergency GuidanceOpen Access53Endocrine ConnectionsG9–G11 G9:5Correspondence  should be addressed  to J Walsh  Email  j.walsh@sheffield.ac.ukSOCIETY FOR ENDOCRINOLOGY  ENDOCRINE EMERGENCY GUIDANCEEmergency management of acute hypercalcaemia in adult patientsJennifer Walsh1, Neil Gittoes2, Peter Selby3 and the Society for Endocrinology  Clinical Committee41The Mellanby Centre for Bone Research, The Medical School, The University of Sheffield, Sheffield, UK2Centre for Endocrinology, Diabetes and Metabolism, University Hospitals Birmingham & University of Birmingham, Birmingham Health Partners, Birmingham, UK3Department of Medicine, Manchester Royal Infirmary, Manchester, UK4The Society for Endocrinology, 22 Apex Court, Woodlands, Bradley Stoke, Bristol, UK10.1530/EC-16-0055IntroductionUnder physiological conditions, serum calcium concentration is tightly regulated. Abnormalities of parathyroid function, bone resorption, renal calcium reabsorption or dihydroxylation of vitamin D may cause regulatory mechanisms to fail and serum calcium to rise. Serum calcium is bound to albumin, and measurements should be adjusted for serum albumin. This guideline aims to take the non-specialist through the initial phase of assessment and management.Severity of hypercalcaemia • Shortened QT interval and dysrhythmias • Nephrolithiasis, nephrocalcinosis • Pancreatitis • Peptic ulceration • Hypertension, cardiomyopathy • Muscle weakness • Band keratopathyCauses<3.0 mmol/L: often asymptomatic and does not usually require urgent correction3.0–3.5 mmol/L: may be well tolerated if it has risen slowly, but may be symptomatic and prompt treatment is usually indicated>3.5 mmol/L: requires urgent correction due to the risk of dysrhythmia and comaClinical features of hypercalcaemia • Polyuria and thirst • Anorexia, nausea and constipation • Mood disturbance, cognitive dysfunction, confusion and coma • Renal impairmentNinety percent of hypercalcaemia is due to primary hyperparathyroidism or malignancyLess common causes include • Thiazide diuretics • Familial hypocalciuric hypercalcaemia • Non-malignant granulomatous disease • Thyrotoxicosis • Tertiary hyperparathyroidism • Hypervitaminosis D • Rhabdomyolysis • Lithium • Immobilisation • Adrenal insufficiency • Milk-alkali syndrome • Hypervitaminosis A • Theophylline toxicity • PhaeochromocytomaDOI: 10.1530/EC-16-0055http://www.endocrineconnections.org © 2016 Society for EndocrinologyPublished by Bioscientifica LtdThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.Emergency Guidance J Walsh et al. Acute hypercalcaemia emergency guidanceG10–G11 5:G10Endocrine ConnectionsInvestigationHistory – Symptoms of hypercalcaemia and duration – Symptoms of underlying causes, e.g. weight loss, night sweats, cough – Family history – Drugs including supplements and over-the-counter preparationsExamination – Assess for cognitive impairment – Fluid balance status – For underlying causes, including neck, respiratory, abdomen, breasts, lymph nodesECG – Look for shortened QT interval or other conduction abnormalitiesBloods – Calcium adjusted for albumin – Phosphate – PTH – Urea and electrolytesHigh calcium and high PTH = primary or tertiary hyperparathyroidism*High calcium and low PTH = malignancy or other less common causes(*Familial hypocalciuric hypercalcaemia may be misdiagnosed as primary hyperparathyroidism due to hypercalcaemia with inappropriately normal or raised PTH. However, the hypercalcaemia is not usually severe and it is less likely to present as an emergency)If further treatment required after intravenous  saline, consider intravenous bisphosphonatesManagementRehydrationIntravenous 0.9% saline 4–6 L in 24 h – Monitor for fluid overload if renal impairment or elderly – Loop diuretics rarely used and only if fluid overload develops; not effective for reducing serum calcium – May need to consider dialysis if severe renal failureZoledronic acid 4 mg over 15 minOR  Pamidronate 30–90 mg (depending on severity of hypercalcaemia) at 20 mg/hOR Ibandronic acid 2–4 mg – Give more slowly and consider dose reduction in renal impairment – Monitor serum calcium response: will reach nadir at 2–4 days – Can cause hypocalcaemia if vitamin D deficiency or suppressed PTHSecond-line treatmentsGlucocorticoids (inhibit 1,25OHD production) – In lymphoma, other granulomatous diseases or 25OHD poisoning – Prednisolone 40 mg daily – Usually effective in 2–4 daysCalcimimetics, denosumab, calcitonin – Under specialist supervision – Can be considered if poor response to other  measuresParathyroidectomy – Can be considered in acute presentation of primary hyperparathyroidism if severe hypercalcaemia and poor response to other measuresDisclaimerThe document should be considered as a guideline only; it is not intended to determine an absolute standard of medical care. The doctors concerned must make the management plan for an individual patient.Sources 1 LeGrand SB, Leskuski D & Zama I. Narrative review: furosemide for hypercalcemia: an unproven yet common practice. Annals of Internal Medicine 2008 149 259–263. (doi:10.7326/0003-4819-149-4-200808190-00007) 2 Nussbaum SR, Younger J, Vandepol CJ, Gagel RF, Zuber MA, Chapman R, Henderson IC & Malette IE. Single-dose intravenous therapy for the treatment of hypercalcaemia of malignancy: DOI: 10.1530/EC-16-0055http://www.endocrineconnections.org © 2016 Society for EndocrinologyPublished by Bioscientifica LtdThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.Emergency Guidance J Walsh et al. Acute hypercalcaemia emergency guidanceEndocrine ConnectionsG11–G11 5:G11Endocrine Connectionscomparison of 30-, 60-, and 90mg doses. American Journal of Medicine 1993 95 297–304. (doi:10.1016/0002-9343(93)90282-T) 3 Major P, Lortholary A, Hon J, Abdi E, Mills G, Menssen HD,  Yunus F, Bell R, Body J, Quebe-Fehling E, et al. Zoledronic acid is superior to pamidronate in the treatment of hypercalcemia of malignancy: a pooled analysis of two randomized, controlled clinical trials. Journal of Clinical Oncology 2001 19 558–567. 4 Wineski LA. Salmon calcitonin in the management of hypercalcaemia. Calcified Tissue International 1990 46 (Supplement) S26–S30. 5 Marcocci C, Chanson P, Shoback D, Bilezikian J, Fernandez-Cruz L, Orgiazzi J, Henzen C, Cheng S, Sterling LR, Lu J, et al. Cinacalcet reduces serum calcium concentrations in patients with intractable primary hyperparathyroidism. Journal of Clinical Endocrinology and Metabolism 2009 94 2766–2772. (doi:10.1210/jc.2008-2640) 6 Rostoker G, Bellamy J & Janklewicz P. Cinacalcet to prevent parathyrotoxic crises in hypercalcaemic patients awaiting parathyroidectomy. BMJ Case Reports 2011 2011 bcr1220103663. (doi:10.1136/bcr.12.2010.3663) Received in final form 3 August 2016Accepted 3 August 2016

SOCIETY FOR ENDOCRINOLOGY ENDOCRINE EMERGENCY GUIDANCE: Emergency management of acute hypercalcaemia in adult patients

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