Malignant Hypercalcaemia

In this second podcast in our new oncology series, Dr Mohammed Farik Jabir, does a lightning 3 minute overview of everything you need to know about malignant hypercalcaemia.

 

Video Duration: 3 minutes

  • Malignant Hypercalcaemia
    Created by Tom Charles
    General
    Epidemiology

    Malignant hypercalcaemia is defined as an excess of calcium in the blood caused by the actions of a tumour or other malignancy.

    Pathology

    Hypercalcaemia, which is usually roughly classed as a blood content of above 2.6mmol/l (The point at which most patients become symptomatic), effects many bodily functions. At the most base level, the excess of calcium blocks sodium channels and its presence in such high levels raises the depolarisation threshold between cells of the nervous and muscular tissues. The high levels of calcium present decrease the membrane permeability of neurons, which leads to muscle hypotonicity. This goes some way to explaining the physical and cognitive sluggishness, weakness and psychiatric symptoms experienced by hypercalcaemic patients.

    The gastrointestinal symptoms of hypercalcaemia can be caused by the stimulation of excess gastrin secretion, leading to nausea, irritation and ulceration, as well as the same issues of excitability causing the neuromuscular issues affecting the cells of the gut, causing constipation.

    Excess calcium can also cause a decrease in heart rate and increase in myocardial contractility. These can lead to unusual ECG readings, including Osborn Waves, an abnormality in heart rhythm usually indicative of hypothermia.

    Top three causes

    - Tumour secretion of calcitriol (also known as 1.25 dehydroxyvitamin D) stimulates calcium absorption in the GI tract and renal resoroption of calcium, forcing more calcium into the bloodstream,

    - Tumour secretion of PTHrP increases the amount of calcium in the blood by mimicking the action of PTH (a hormone usually used to stimulate calcium retention in the event of slight calcium deficit) and binding to the PTHR1 receptor, stimulating bone resorption and resorption in the distal tubules. Stimulation of this natural calcium regulation process in an inappropriate circumstance causes an excess of calcium in the blood.

    - Bone metastases induce osteoclastic activity and increase bone resorption of calcium.

    Clinical Features
    Symptoms

    Hypercalcaemia presents with classic symptoms that follow a handy pnemonic:

    Stones: The formation of renal or biliary stones is a classic symptom of hypercalcaemia.

    Bones: Bone pain is a common presenting symptom.

    Groans: Abdominal pains, nausea, vomiting.

    Thrones: Polyuria - patients may complain of passing an unusually large amount of urine, or urinating far more frequently without any change in how much they drink.

    Pshychiatric Overtones: Depression is a common presenting symtom in hypercalcaemia, as well as anxiety, some degree of cognitive impairment or sluggishness. Symptoms may progress towards insomnia and coma without adequate intervention.


    Signs

    Limbus sign - Calcification of the corneal limbus (where the cornea meets the sclera) presents as a ring of milky precipitate, and is indicative of high serum calcium content.

    Anorexia or remarkable weight loss can be a symptom.

    Short QT interval on ECG is suggestive of hypercalcaemia.

    Presence of Osborn Wave on ECG without hypothermia is also indicative of hypercalcaemia, among a select few other conditions.

    Investigations
    Cultures

    None

    Bloods

    Blood calcium (for obvious reasons)

    Blood phosphates (if parathyroid implication is suspected)

    Imaging

    Bone scan with tracer (If bone metastasis is suspected)

    Scopic/Biopsy

    None

    Functional

    ECG (Can detect abnormalities associated with hypercalcaemia)

    Treatment
    Conservative

    IV fluids - dysfunction of renal tubules can lead to dehydration, exacerbating symptoms. After this rehydration, a loop diuretic (e.g Furosemide) can be given to prevent blood volume overload.

    Reduction of dietary calcium intake - limiting the amount of calcium entering the body is advisable.

    Medical

    Bisphosphonates (e.g IV Zoledronate) inhibit bone resorption of calcium, and calcitonin does the same while encouraging urinary excretion of calcium by inhibiting renal resorption of calcium.

    Surgical

    None