Hypercalcemia

What is calcium and why is it important?

Calcium is a mineral found in small quantities throughout the body. It plays an important role in vital bodily functions, including muscle contraction, transmission of nerve impulses, blood clotting, and bone growth.

What is hypercalcemia?

Hypercalcemia occurs when the level of calcium in the blood is higher than normal (hyper = “above”; -emia = “blood”).

How are calcium levels controlled in healthy animals?

Calcium levels are controlled by a pair of parathyroid glands. The two tiny glands are embedded in the thyroid gland, which sits just below the larynx or "voice box", on the windpipe. 

When calcium levels are too low, the parathyroid glands release a hormone called parathyroid hormone (PTH), which acts to return calcium levels to normal.

Why is having high calcium bad for my pet?

High calcium levels may signal the presence of serious underlying disease, including kidney failure, adrenal gland failure (called Addison's disease), a parathyroid gland tumor, and some types of cancer.

"Pets with abnormally high calcium levels may show signs of weakness, listlessness, increased drinking and urination, and loss of appetite."

Pets with abnormally high calcium levels may show signs of weakness, listlessness, increased drinking and urination, and loss of appetite. In some pets, prolonged hypercalcemia may contribute to the formation of bladder stones or kidney stones. Mineralization can also occur in other organ systems.

How are calcium levels measured?

Two forms of calcium are found in blood: total calcium and ionized calcium (also called free calcium). 

• Total calcium: The test for total calcium is simple, rapid, and relatively inexpensive. It is typically used as a preliminary test to measure calcium levels. However, total calcium can be falsely increased by diet and dehydration, making it an unreliable test in some situations. If preliminary testing reveals hypercalcemia, then it is often recommended to measure ionized calcium to confirm the finding.
• Ionized calcium: The test for ionized calcium is the definitive test for measuring blood calcium levels; however, it is more difficult to perform than total calcium, requires patient fasting, and requires special sample handling. It is usually more expensive and often takes longer to get results back from the laboratory.

What further testing is required if my pet has high total calcium on a routine blood test?

If there is no evidence of a disease that might explain the high calcium (e.g., renal failure, Addison’s disease etc.), then total calcium should be re-measured on a fresh blood sample to confirm the result. Repeat testing is warranted if diet or dehydration may have contributed to the high initial value.

"Repeat testing is warranted if diet or dehydration may have contributed to the high initial value."

Before repeating total calcium, the pet should be fasted for 12 hours but must have access to water. A test to measure albumin (a blood protein) should be done at the same time to check that the pet is not dehydrated. If the repeated value for total calcium is still high on the re-test, then an ionized calcium test is recommended, since it is the definitive test for measuring calcium levels.

Once hypercalcemia is confirmed, the challenge is to identify the underlying cause. Further testing will be needed to assess the health of the kidneys, adrenal glands, and parathyroid glands. If there is a history of vitamin D supplementation, testing for levels of vitamin D is appropriate. Your veterinarian may also want to examine your pet for signs of underlying cancer.

Why is measuring parathyroid hormone (PTH) important?

Since the parathyroid glands control calcium levels, it is important to know that these glands are working properly, and measuring parathyroid hormone (PTH) levels is the easiest way to determine this. PTH levels may also provide clues about what is causing hypercalcemia.

• If a pet has both hypercalcemia and high levels of parathyroid hormone, then a diagnosis of hyperparathyroidism can be made. There are two main types of hyperparathyroidism: primary hyperparathyroidism is caused by a tumor in the parathyroid glands and secondary hyperparathyroidism is the result of longstanding kidney disease or poor nutrition.
• If a pet has hypercalcemia but has low levels of parathyroid hormone, then it suggests there has been a breakdown in the normal mechanism that controls calcium levels, and may mean there is an underlying cancer. The pet should be thoroughly examined and additional diagnostic tests may be recommended, including radiography, ultrasound, cytology, or biopsy.

If cancer is suspected, then a specialized blood test can be performed that measures a substance called parathyroid hormone-related protein (PTH-rP). This hormone-like substance is produced by certain cancers, and it acts like parathyroid hormone even though it is distinctly different from the normal hormone. If this substance is found in high levels in the blood, then underlying cancer is likely present. Cancers that can form PTH-rP may include lymphoma, multiple myeloma, and anal gland tumors.

In some pets, no cause can be found for elevated calcium, despite extensive testing. It is then termed idiopathic hypercalcemia, which is a diagnosis of exclusion.  It is rare in dogs but one of the most common forms in cats.