Hypercalcaemia

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 (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 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)

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?)
Sarcoidosis
CXR (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

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

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

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