Hypercalcaemia
Hypercalcaemia - key facts
Authors: Kate Outterside, Sailesh Sankar, Ateeq Syed
Top Tip: Hypercalcaemia is easy to treat. If severe, contact your nearest Renal Unit
| Key Differential Diagnosis | Hyperglycaemia |
| Key Investigations |
FBC, ESR, CRP U+E, LFT, Bone, Glucose Phosphate, Alk Phos, PTH, Mg, PSA ECG, CXR |
| Key Treatment |
IV + FLUIDS (unless fluid overloaded) ± PO/IV FUROSEMIDE 40-80 mg od ± IV DISODIUM PAMIDRONATE 15-60 mg over 30 mins via wide bore cannula in large vein |
| Key Management Decision | Dialysis |
Hypercalcaemia - background
| Introduction |
• Hypercalcaemia (hypercalcemia) is often a clue to the presence of unsuspected illness • It is common, present in 5% of hospitalised patients (often not the primary problem, or cause of admission) • The majority of hospital inpatients with elevated serum calcium will be found to have malignancy (including myeloma). The majority of outpatients will have non-neoplastic disease especially primary hyperparathyroidism; although the differential diagnosis in both in- and outpatients is much wider (see below) • Treatment is IV saline plus FUROSEMIDE and sometimes bisphosphonates Hypercalcemia Today. Yousuf K et al, 2006 (pdf) |
| Definition | (Adjusted) serum calcium level > 2.6 mmol/L |
| Types |
Mild = 2.6-2.9 Moderate = 3.0-3.4 Severe = 3.5+ |
| Causes |
3 important causes (90%): • Hyperparathyroidism (primary; secondary/tertiary in CRF) • Malignancy (breast, lung, prostate, ovary, kidney) • Myeloma Others (10%) include: • Sarcoidosis (Sarcoidosis. Baughman RP. Lancet; 361 (9363): 1111 - 1118, 2003) and Tuberculosis • Drugs: thiazide diuretics, vitamin D/calcium salts (especially if patient has CRF), vitamin A intoxication, lithium • Endocrine (eg thyrotoxicosis, acromegaly, hypoadrenalism, phaeochromocytoma) • Immobilisation (prolonged in patients with high bone turnover, eg Paget's) • Milk alkali syndrome • Other: some fungal infections, rhabdomyolysis (calcium low then high), familial hypocalciuric hypercalcemia (FHH) Rare Causes of Hypercalcemia. Jacobs PT et al. J Clin Endocrinol Metab; 90 (11): 6316-6322, 2005 |
| Erythema Nodosum (a feature of 2 causes of hypercalcaemia: TB and sarcoidosis) |
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| Causes of Erythema Nodosum |
Erythema nodosum is often indicative of an underlying infectious disease but a cause is not always found Infectious: • Streptococcal infection (commonest cause); and Mycoplasma pneumonia; it may be a feature of other diseases including scarlet fever and rheumatic fever although in the UK nowadays the former is uncommon and the latter rare • Tuberculosis / Leprosy • Gastroenteritis; especially Yersinia enterocolitica, Salmonella, and Campylobacter • Fungal infections; less common in the UK but coccidioidomycosis is important in the south-west USA. It may also occur in histoplasmosis and blastoplasmosis. Non-infectious: • Sarcoidosis • Drugs: sulphonamides, sulphonylureas, gold and oral contraceptives • Crohn's disease / ulcerative colitis • Hodgkin's disease and non-Hodgkin's lymphoma (can precede by months) • Behçet's syndrome • Pregnancy (usually in the second trimester). It is likely to recur in future pregnancies and may occur with oral contraceptives Note: in many cases no cause is found |
| Symptoms |
None (50%+), especially if mild; symptoms usually mean hypercalcaemia is severe (3.5+ mmol/L) Dermatological: itching, red eyes 'Bones': bone pain/fracture 'Groans' (GI): nausea, vomiting, constipation 'Stones' (Renal): polyuria/polydipsia; loin pain 'Psychic moans' (Psychiatric): depression/confusion Neurological: weakness, hypotonicity Of underlying disease (eg bone pain in myeloma) |
| Key questions |
"When did the symptoms start?" "Any pain in your bones?" |
| Signs |
None (if mild) Dehydration Red eyes If severe, reduced level of consciousness/fits Of underlying disease (eg clubbing secondary to lung carcinoma, breast lump) |
Hypercalcaemia - investigation
| Blood |
FBC, ESR, CRP U+E, LFT, Bone (especially calcium, phosphate, alk phos) Glucose PTH (key investigation, raised in hyperparathyroidism, low otherwise), Mg, PSA |
| Other |
ECG (bradycardia? AV block? shortened QT interval?) SarcoidosisCXR (malignancy? fractures?; sarcoidosis?)  KUB (nephrocalcinosis)
|
| Key investigation | Calcium |
| Specialist investigation |
PTH (absent in non-PTH causes) Bone scan (bone metastases) Protein electrophoresis, Bence-Jones proteinuria (both myeloma) |
| Differential Diagnosis |
Hyperglycaemia (polyuria/polydipsia) Other causes bone pain |
Hypercalcaemia - treatment
|
Treatment (first line) |
Procedures: IV line (and a lot IV fluid, unless fluid overloaded; most will be very dry) Note: initial Rx may be different, if patient has CRF, and known to renal team; contact them, if this is the case Drugs: ± PO/IV FUROSEMIDE 40-80 mg od, if clinically appropriate |
| Key management decision | Dialysis/not |
| Stop | Vitamin D/calcium salts, thiazide diuretics |
|
Treatment (second line) |
Drugs: ± IV DISODIUM PAMIDRONATE 15-60 mg; can give upto 90 mg if Calcium > 3.5 mmol/L; over 30 mins (via wide bore cannula in large vein); works over 2-3d, max effect 1 week; decrease dose in renal failure, and give more slowly (<20 mg/hr) ± PREDNISOLONE/METHYLPREDNISOLONE (in haematological malignancies, sarcoidosis + vitamin D excess; ineffective in PTH disease) Procedures: If unwell, urinary catheter, CVP line, arterial line Haemodialysis (against low calcium dialysate), if calcium does not fall despite all above |
| Prescribing issues | Allow DISODIUM PAMIDRONATE to work, peaks at 2-3 days; reduce dose in renal failure; look at local hypercalcaemia protocol |
| Admit? | Usually, especially if calcium > 3.0 mmol/L |
| Bed plan |
Medical admission ward, if admission predicted to be <48 hrs Endocrinology, or haematology/oncology, or renal; if admission predicted to be >48 hrs ± ITU |
| Referrals |
Variable (vs cause): Endocrine, or Haematology/oncology, or Renal ± ITU |
Hypercalcaemia - the rest
| Complications |
• ARF (polyuria) • Reduced conscious level • Fits |
| Follow-up | According to cause |
| Prognosis | If associated with malignancy, prognosis is poor; one year survival = 10-30%. The prognosis of sarcoidosis (and other causes of non malignant hypercalcaemia) is good |
|
Risk stratification (who can be managed as outpatient) |
If calcium < 3.0, and well |
|
2° Prevention + Health promotion |
Attend specialist follow-up appointments Know you own calcium level at all times |
| Don't forget |
• Majority of inpatients have malignancy (includng myeloma) • Look at CXR and examine breasts • DRUGS DRUGS DRUGS • Contact specialist if patient has one |
| Red flags |
• Calcium = 3.5+ • Reduced conscious level • Fits |