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
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 [Ref]
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 [Ref] 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)[Ref]
Erythema Nodosum (a feature of 2 causes of hypercalcaemia: TB and sarcoidosis)
Causes of Erythema Nodosum
Erythema nodosum is often indicative of an underlying infectious disease but a cause is not always found. Causes include:
- 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)
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?)
- CXR (malignancy? fractures?; sarcoidosis?)
Key investigation
- Calcium
Specialist investigations
- PTH (absent in non-PTH causes)
- Bone scan (bone metastases)
- Protein electrophoresis, Bence-Jones proteinuria (both myeloma)
Differential diagnoses
- Hyperglycaemia (polyuria/polydipsia)
- Other causes bone pain
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
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, if an 'at risk' patient (eg dialysis or kidney transplant)
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
