Key facts:
Authors: Kate Outterside, Sailesh Sankar, Ateeq Syed
Top Tip: Hypercalcaemia is easy to treat. If severe, contact your nearest Renal Unit
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Key Differential Diagnosis
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Hyperglycaemia
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Key Investigations
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FBC, ESR, CRP U+E, LFT, Bone, Glucose Phosphate, Alk Phos, PTH, Mg, PSA ECG, CXR
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Key Treatment
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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
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Key Management Decision
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Dialysis
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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
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Definition
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(Adjusted) serum calcium level > 2.6 mmol/L
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Types
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Mild = 2.6-2.9 Moderate = 3.0-3.4 Severe = 3.5+
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Causes
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3 important causes (90%): • Hyperparathyroidism (primary; secondary/tertiary in CRF) • Malignancy (breast, lung, prostate, ovary, kidney) • Myeloma Others (10%) include: • Sarcoidosis
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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)
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| 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
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Symptoms
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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)
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Key questions
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"When did the symptoms start?" "Any pain in your bones?"
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Signs
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None (if mild) Dehydration Red eyes If severe, reduced level of consciousness/fits Of underlying disease (eg clubbing secondary to lung carcinoma, breast lump)
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Investigation
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Blood
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FBC, ESR, CRP U+E, LFT, Bone (especially calcium, phosphate, alk phos) Glucose PTH (key investigation, raised in hyperparathyroidism, low otherwise), Mg, PSA
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Other
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ECG (bradycardia? AV block? shortened QT interval?)
Sarcoidosis CXR (malignancy? fractures?; sarcoidosis?)
KUB (nephrocalcinosis)
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Key investigation
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Calcium
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Specialist investigation
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PTH (absent in non-PTH causes) Bone scan (bone metastases) Protein electrophoresis, Bence-Jones proteinuria (both myeloma)
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Differential diagnosis
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Hyperglycaemia (polyuria/polydipsia) Other causes bone pain
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Treatment
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Treatment (first line)
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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
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Key management decision
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Dialysis/not
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Stop
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Vitamin D/calcium salts, thiazide diuretics
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Treatment (second line)
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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
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| Prescribing issues |
Allow DISODIUM PAMIDRONATE to work, peaks at 2-3 days; reduce dose in renal failure; look at local hypercalcaemia protocol |
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Admit?
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Usually, especially if calcium > 3.0 mmol/L
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Bed plan
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Medical admission ward, if admission predicted to be <48 hrs Endocrinology, or haematology/oncology, or renal; if admission predicted to be >48 hrs ± ITU
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Referrals
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Variable (vs cause): Endocrine, or Haematology/oncology, or Renal ± ITU
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The Rest
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Complications
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• ARF (polyuria) • Reduced conscious level • Fits
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Follow-up
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According to cause
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Prognosis
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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
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Risk stratification (who can be managed as outpatient)
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If calcium < 3.0, and well
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2° Prevention + Health promotion
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Attend specialist follow-up appointments Know you own calcium level at all times
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Don't forget
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• Majority of inpatients have malignancy (includng myeloma) • Look at CXR and examine breasts • DRUGS DRUGS DRUGS • Contact specialist if patient has one
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Red flags
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• Calcium = 3.5+ • Reduced conscious level • Fits
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References