Table of Contents
- Overview
- Triage
- Causes
- Clinical features
- Investigations
- Management - Symptomatic Moderate and Severe Hypercalcaemia
- Management principles of severe hypercalcaemia involve (4):
- *Note that management of the different causes of hypercalcaemia is specialised knowledge and will likely require endocrinology input. As a junior medical officer, you are expected to order intravenous fluid and initial investigations before contacting endocrinology for further advice.
- 1. Intravenous fluid
- 2. If life threatening hypercalcaemia e.g. arrhythmia
- 3. Antiresorptive Medications
- 4. If caused by granulomatous disease or Vitamin D toxicity
- Management - Mild and Asymptomatic Moderate Hypercalcaemia
- References
Overview #
- Hypercalcaemia – serum calcium >2.60 mmol/L
- Serum calcium (ref range 2.10-2.60 mmol/L) – a measure of the total amount of serum calcium. May be falsely reduced with hypoalbuminaemia and falsely elevated with hyperalbuminaemia.
- Corrected calcium (ref range 2.10-2.60 mmol/L) – calcium adjusted for albumin, only valid for albumin levels 30-50 g/L.
Ionised calcium (ref range 1.15-1.30 mmol/L) – the primary determinant of physiological effects of hypercalcaemia
Triage #
- Severe hypercalcaemia (>3.20 mmol/L or arrhythmia present) – immediate attention (risk of cardiac arrhythmia)
- Symptomatic moderate hypercalcaemia (2.90-3.20 mmol/L) – attention is required within the hour to prevent progression, whilst asymptomatic patients can be seen within several hours
- Mild asymptomatic hypercalcaemia (2.60-2.90 mmol/L) – non urgent
Causes #
90% of hypercalcaemia is caused by primary hyperparathyroidism (more common in the community) and malignancy (more common in hospitals) (2).
*Adapted from Marshall and Ruedy’s On Call: Principles & Protocols (3)
Parathyroid Disorders #
- Hyperparathyroidism
- Primary {{Disorder of the parathyroid, leading to increased PTH production and therefore hypercalcaemia. Most commonly caused by parathyroid adenoma}}
- Secondary {{Reversible elevated PTH secretion from a cause external to the parathyroid. Most commonly caused by chronic kidney disease, decreased calcium intake or vitamin D deficiency}}
- Tertiary {{Progression of secondary hyperparathyroidism to parathyroid gland autonomy, where correction of the underlying cause does not stop excess PTH secretion}}
- Familial hypocalciuric hypercalcaemia
Malignancy #
- Bony metastases
- Multiple myeloma and other lymphoproliferative disorders
- Paraneoplastic syndrome where squamous cell carcinomas produce PTH-related peptide (PTH-rp)
Vitamin D/Calcium Disorders #
- Excessive calcium supplementation
- Milk-alkali syndrome
- Granulomatous diseases leading to excess calcitriol e.g. sarcoidosis and tuberculosis
- Vitamin D toxicity
High Bone Turnover #
- Hyperthyroidism
- Paget’s Disease
- Vitamin A toxicity
- Immobilisation
Miscellaneous #
- Thiazide diuretic use
- Chronic lithium use
- Acromegaly
- Addison’s Disease
- Prolonged tourniquet prior to blood draw
- Dehydration
- Hyperalbuminaemia (artefactual and not requiring treatment)
Clinical features #
Symptoms #
Symptoms of hypercalcaemia can be remembered with the mnemonic: “stones, bones, groans, moans, thrones, muscle tones, psychiatric overtones”.
- Kidney stones (“stones”)
- Bone pain, fractures (“bones”)
- Abdominal pain (“groans”)
- Fatigue, nausea, vomiting (“moans”)
- Constipation (“thrones”)
- Muscle weakness (“muscle tones”)
- Depression, anxiety (“psychiatric overtones”)
Signs #
- Hyporeflexia
- Muscle weakness
- Abdominal tenderness
- Altered GCS and coma
Investigations #
Initial Investigations #
| Investigation | Significance |
| ECG | In severe hypercalcaemia to assess for arrhythmias |
| Corrected Calcium | To factor in albumin’s effect on serum calcium |
| Ionised Calcium | If available, able to determine the physiological effects of calcium |
| PTH | Used to differentiate hyperparathyroidism and vit D deficiency vs other causes |
| UEC | Assessing for renal failure for secondary/tertiary hyperparathyroidism |
| 25-hydroxyvitamin D | Elevated in vitamin D intoxication |
Further Investigations
| Investigation | Indication |
| Malignancy Screen | |
| FBE | Anaemia, leukocytopenia and thrombocytopenia could suggest malignancy |
| LFT | Deranged LFTs could suggest liver metastases |
| Multiple Myeloma Screen(Callout box: SPEP, UPEP, serum free light chains assay) | If multiple myeloma suspected |
| Chest XR | Assessing for paraneoplastic syndrome. Can also show granulomatous disease e.g. sarcoidosis, tuberculosis |
| Other Causes | |
| 1,25-dihydroxyvitamin D | Elevated in lymphoma, and granulomatous diseases e.g. sarcoidosis |
| Thyroid Function Tests | Assessing for hyperthyroidism |
Management – Symptomatic Moderate and Severe Hypercalcaemia #
Management principles of severe hypercalcaemia involve (4): #
- Expanding the extracellular fluid volume with intravenous fluid.
- In life threatening hypercalcaemia, for example a patient with heart arrhythmia, synthetic calcitonin can be used to rapidly decrease calcium levels.
- Adjuncts such as bisphosphonates can be used to further lower calcium levels depending on the cause of hypercalcaemia.
*Note that management of the different causes of hypercalcaemia is specialised knowledge and will likely require endocrinology input. As a junior medical officer, you are expected to order intravenous fluid and initial investigations before contacting endocrinology for further advice. #
1. Intravenous fluid #
| 0.9% Sodium Chloride running initially at a rate of 200-300ml/hr and adjusting to maintain a urine output of 100-150ml/hrBeware – patients with CCF or CKD are at risk of becoming fluid overloaded and require careful monitoring. #IV frusemide may be started under specialist supervision |
2. If life threatening hypercalcaemia e.g. arrhythmia #
| #Calcitonin 100IU Subcut/IM/IV every 8-12 hours |
3. Antiresorptive Medications #
| #Zoledronic Acid 4mg IV over 15 minutesOR #Disodium Pamidronate 60-90mg infusion in 1000ml 0.9% normal saline over 4 hours (Pamidronate is generally more rapid acting than zoledronic acid)Adjust – Dose reduce Zoledronic Acid if CrCl<60 OR#Denosumab if eGFR is between 15 and 30 |
4. If caused by granulomatous disease or Vitamin D toxicity #
| #Prednisolone 15-30mg PO daily |
Management – Mild and Asymptomatic Moderate Hypercalcaemia #
For mild asymptomatic hypercalcaemia, immediate treatment may not be required and time can be spent to investigate the cause. For moderate, asymptomatic hypercalcaemia, intravenous fluids (i.e. sodium chloride) can be commenced to expand the extracellular fluid and reduce the calcium concentration and further investigations should be performed to identify the cause.
References #
- Yu A, Subbs J. Relation between total and ionized serum calcium concentrations. In: Goldfarb S, Geffner M, Lam A.;UpToDate. [Internet]. Waltham (MA): UpToDate Inc; 2017. [updated 2021 May 07; cited 2021 Aug 29]. Available from: https://www-uptodate-com.monash.idm.oclc.org/contents/relation-between-total-and-ionized-serum-calcium-concentrations?search=hypercalcaemia&topicRef=850&source=see_link
- Shane E. Diagnostic approach to hypercalcaemia. In: Rosen C, Mulder J.;UpToDate. [Internet]. Waltham (MA): UpToDate nc; 2017. [updated 2020 Aug 31; cited 2021 Aug 20]. Available from: https://www-uptodate-com.monash.idm.oclc.org/contents/diagnostic-approach-to-hypercalcemia?search=hypercalcaemia&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1
- Brown A, Cadogan M, Celenza A. Marshall & Ruedy’s On Call: Principles & Protocols. 3rd Ed. Chatswood: Elsevier Australia; 2017. p. 406-412.
- eTG complete [Internet]. Melbourne (Vic): Therapeutic Guidelines Ltd; 2017. Hypercalcaemia [updated 2021 Mar; cited 2021 Sep]. Available from: https://tgldcdp-tg-org-au-acs-hcn-com-au.monash.idm.oclc.org/viewTopic?topicfile=hypercalcaemia&guidelineName=Bone%20and%20Metabolism&topicNavigation=navigateTopic
Contributors
Reviewing Consultant/Senior Registrar
Dr Bill Chow
Dr Rahul Barmanray
