Cancer and blood calcium in pets: what is the link? 

Why is calcium important in the body? 

Calcium is extremely important in the body not only for teeth and bones, but it also helps to control the way that all muscles and organs (including the brain, kidneys, and bowels) function. It is particularly essential for muscle contraction, initiating nerve signals, and stabilising nerve cell membranes. Both too much calcium and too little can cause serious problems. 

How are normal calcium levels maintained? 

The amount of calcium in the blood is tightly regulated by parathyroid hormone (PTH). This hormone is produced by the parathyroid glands, which are four small glands found in your pet’s neck. These glands are only 2-3mm in length, but their job is very important. If they produce too much parathyroid hormone can cause calcium levels around the body to rise, and too little of this hormone can cause them to decrease.  Either way, the animal can become very unwell. 

Problems can occur with the parathyroid glands themselves, in the case of primary hyperparathyroidism and hypoparathyroidism, but there are also other disease processes that can impact your pet’s blood calcium. The most common cause of hypercalcaemia in pets is due to cancer, with about 45% to 65% of hypercalcaemic dogs and 10% to 30% of hypercalcaemic cats having underlying cancer. 

What is the link between cancer and elevated blood calcium? 

There is a phenomenon known as pseudohyperparathyroidism, which can be caused by malignant cancer.  In this condition, we see calcium levels increase in certain types of cancer, including lymphoma or anal gland tumours. 

The mechanism is complex – the MSD Veterinary Manual states – “Paraneoplastic mechanisms of hypercalcemia include tumor production and release of soluble mediators (such as parathyroid hormone–related protein [PTHrP], interleukin-1 and interleukin-6 [IL-1, IL-6], and calcitriol) by tumor cells into circulation; release of osteoclast-activating factors by bony metastatic lesions; excessive production of 1,25-dihydroxyvitamin D; and excessive production of parathyroid hormone (PTH)”. 

Simply put, many of these tumours release proteins, some of which have a similar structure to parathyroid hormone, including parathyroid hormone-related protein (PTHrP). This causes calcium levels in the body to rise. 

Not only is the malignant cancer itself problematic, but elevated blood calcium levels can cause issues too, such as kidney damage.  Sadly, in many cases, hypercalcaemia of malignancy carries a guarded to poor prognosis.  

What are the symptoms of high blood calcium?  

Symptoms of high blood calcium can sometimes be vague and non-specific. Some animals are completely asymptomatic, with the issue only being picked up after a routine blood test shows an abnormality. Possible symptoms could include – 

• Increased thirst 

• Increased urination  

• Lethargy  

• Weakness  

• Reduced appetite  

• Vomiting  

• Constipation  

• Bladder and kidney stones  

• Muscle tremors  

• Seizures  

Animals with malignant tumours may also show symptoms specific to their cancer, such as enlarged lymph nodes (glands), a mass, or skin sores.  

My pet has high blood calcium levels – what happens next? 

A blood test is often recommended for pets that are unwell, so that your vet can try to work out what is going on. An elevation in calcium levels on a blood test can raise their suspicions of a cancerous process, but it is not diagnostic. Further tests and examinations will need to be done to get to the bottom of the problem. 

Physical examination 

When you bring your pet into the vet, they will perform a physical examination and discuss any symptoms with you. As part of their examination, they will do routine checks like assessing your pet’s heart, temperature, and mucous membrane colour. 

They will also feel your pet’s lymph nodes for any sign of enlargement, which could indicate a problem like lymphoma. Peripheral lymph nodes can be felt in the neck area just under the jaw (submandibular), near your pet’s shoulders (prescapular), and the backs of their legs (popliteals). They will also feel your pet’s abdomen for any signs of organ enlargement or discomfort. In dogs, a rectal exam will allow your vet to feel their anal glands/sacs, as small tumours here can cause problems. 

Blood tests 

As part of your pet’s initial bloodwork, they may have their haematology checked which looks at their levels of red blood cells and white blood cells, giving markers for inflammation or infection. A biochemistry screen is usually carried out to screen things like their liver and kidney parameters, blood sugar, and protein levels. 

Electrolytes are also often tested, which looks at potassium, sodium, and calcium levels. This particular blood screen usually looks at something called the total calcium level in the blood. If this is elevated, your vet will often recommend doing an ionised calcium blood test , which looks at biologically active calcium in the blood. This gives us more information than just looking at your pet’s total calcium alone. Ionized calcium concentrations > 1.4 – 1.5 mmol/L are considered in the hypercalcaemic range. 

Your vet may also decide to run tests that look at PTH, vitamin D, and PTHrP concentrations. This is not usually required if the cause of the high blood calcium levels is obvious, for example, enlarged lymph nodes or a tumour is found on physical examination or imaging. But if needed, these tests can help to differentiate between a problem with the parathyroid glands or a possible underlying malignant tumour process. 

Diagnostic imaging 

Imaging can be helpful to look for a tumour or to try to get an understanding of the tumour’s severity. X-rays are commonly performed, which can help vets see your pet’s chest, allowing them to look for masses or for tumour spread (metastasis). Images of the abdomen can also help to identify things like organ enlargement. X-rays of bones can also help to identify bone tumours, especially in a patient who has been limping or painful. 

Ultrasound scans can help vets to look at certain areas of the body in more detail, as well as assess for abnormalities like free fluid. Advanced diagnostic imaging is also useful, such as a CT scan (Computed Tomography). This can give even more information about tumours and their spread.  

Samples 

Sometimes samples are needed to make a definitive diagnosis and find out more about the type of tumour your pet has. Fine needle aspirates involve inserting a small needle into the mass or lymph node, drawing out cells to look at under the microscope. A biopsy can give more information still, but it involves actual tissue from the lump being sent away for analysis. A biopsy may involve a small piece of tissue being cut out (incisional) or the whole lump (excisional).   

Common types of cancer that cause hypercalcaemia  

The following is a list of common tumour types that can cause elevated blood calcium levels –  

• Lymphoma 

• Apocrine anal sac adenocarcinoma 

• Multiple myeloma 

• Thymoma 

• Melanoma 

• Mammary tumours 

• Bone tumours   

• Parathyroid tumours (though these are often benign) 

Treatment and prognosis for these various cancers vary, so your vet will be able to advise you further, depending on your pet’s diagnosis. 

Treatment of hypercalcaemia of malignancy 

Steps can be taken to try to improve your pet’s condition. This may involve hospitalisation for medication and intravenous fluids to correct dehydration. Bisphosphonates can help to reduce calcium levels in affected pets, which may need to be given via their drip. Diuretics like furosemide may be used. Steroid treatment can also be helpful, but must only be used after the type of cancer has been diagnosed and a proper treatment plan formulated, as they can cause resistance to certain chemotherapy agents, which may affect how the underlying cancer is managed. 

Treatment for the tumour itself can be more complicated and will depend on multiple factors such as the tumour’s size, location, and type. Surgical removal may be possible for some tumours, and chemotherapy protocols can also help to improve lifespan. However, owners should bear in mind that some malignant tumours are aggressive and may not be readily treatable. Elevated calcium levels can also directly cause damage to organs like the kidneys, which may not be reversible.  

What’s my pet’s long-term outlook? 

Hypercalcaemia can occur due to several different disease processes, so this means prognosis is often guarded but can be variable. As with most things, prompt identification and treatment of the problem will generally lead to better outcomes. 

In the case of hypercalcaemia of malignancy, removal of the cancer by surgery, or achieving clinical remission with chemotherapy or radiation therapy, will be the most effective treatment option. In the short term, most patients will feel better with supportive treatment to reduce their calcium levels via intravenous fluids and other medications. This treatment may need to be started while your vet works out the underlying cause of their hypercalcaemia. The success of any treatment in the longer term will depend on the diagnosis, as the tumour type and how progressed it is will affect prognosis.  

Your vet will consider the whole clinical picture, however, when deciding a treatment plan. Generally, patients with the following will show a much poorer chance of long-term survival –  

• Clinically ill patients due to a hypercalcemia in excess of 16 mg/dL (4 mmol/L), 

• Pets with severe kidney damage (renal azotaemia) 

• Dogs that have a calcium and phosphorus product greater than 60, causing abnormal calcium formation (metastatic mineralization) in the body 

• Patients suffering from hypercalcemia of malignancy that is associated with solid tumours, which cannot be surgically removed 

In some cases, euthanasia will be recommended to prevent ongoing suffering. This can be a tough time for many pet owners, especially if your pet’s illness has developed suddenly.  Your vet will be able to talk you through this decision and help guide you. 

Summary 

Elevated blood calcium levels can occur due to several different disease processes, but malignant cancer is the most common cause in pets. Your pet’s prognosis will depend on the type of cancer, how far it has progressed, and what treatment options are available. Your vet will be able to guide you through the recommended tests and potential treatments, including euthanasia if this is in the best interests of your pet. If you have any concerns about your pet’s health or diagnosis, then don’t be afraid to speak to your vet for more detailed advice.