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Hypercalcemia (High calcium in the blood)


High calcium in the blood is due to parathyroid disease almost all the time. High calcium (hypercalcemia) is never normal. All causes of high calcium are discussed here; including what tests will determine the cause of the high blood calcium. No worries, high blood calcium are rarely cancer!
 

High blood calcium is not normal. If you have a blood test that shows high blood calcium, then your doctor is obligated to check it out. It is never normal to have high calcium levels in your blood. Hypercalcemia is the medical term for high blood calcium. Over 98% of all cases of too much blood calcium are due to parathyroid disease and hyperparathyroidism. Parathyroid disease is the cause of high calcium at least 98% of the time.
There is a lot written about high calcium being caused by cancer, however, this is not very common.
It is very RARE for high blood calcium to be due to cancer


 

Causes of High Blood Calcium and Too Much Calcium in the Blood.

 

1- Hyperparathyroidism (abnormal function of the parathyroid glands).


Over 98% of ALL people who have a blood test that shows too much calcium will have a parathyroid problem. Parathyroid glands are little glands in the neck that control the calcium in the blood. Occasionally one of them will grow into a benign tumor and cause high blood calcium. It is virtually 100% benign (not cancer), can be cured in most people, and is almost always associated with some symptoms. Parathyroid disease is the cause of almost all high calcium levels. It must be fixed. It should not be ignored or watched.

 

Tests needed:
In summary, you need to have your calcium and PTH measured. Preferably, you should have TWO different types of blood calcium measured: 1) serum calcium, and 2) ionized calcium. Parathyroid Hormone (PTH) must also be measured.  This is all that is needed to make the diagnosis of hyperparathyroidism in more than 95% of patients. You do NOT need any x-rays or scans to make the diagnosis of hyperparathyroidism.
 

2- Cancer  (less than 1% of cases of high calcium are due to cancer, far less than 0.01% of cases of high calcium in people sitting in front of their computer are due to cancer) (you don’t have cancer!).
 


Cancer is a catch-all phrase that includes 122 different types of malignancies known to occur in humans. Of those 122 types of cancer, there are 5 that are known to be associated with high calcium levels in the blood. About 10% to 15% of people with one of these types of cancer will have a high calcium level at one time or another. Very high blood calcium (above 13) is the most common life-threatening emergency associated with these cancers, and is typically seen at the end-stage of the cancer (end-stage means the patient is in real bad shape and near the end). 
Thus, we can take several lessons away from these facts:
1) Cancer is almost never detected in a patient because the doctor noticed a high calcium level (this isn’t how cancers present themselves),

2) High calcium due to cancer almost always occurs in people who are quite sick from their cancer it’s not a surprise that they have cancer,

3) High calcium due to cancer is usually found in people who are in the hospital—they are sick from the cancer,

4) If you have high calcium and you aren’t sick from cancer, then you are almost guaranteed to you have a parathyroid problem and not cancer.
 


The types of cancer known to be associated with high blood calcium are:

1- Multiple Myeloma
2- Lung Cancer (squamous cell cancer of the lung, not all lung cancers)
3- Breast Cancer (advanced disease)
4- Kidney Cancer
5- Squamous Cell Cancer of the Head and Neck

Cancer causes hypercalcemia (high blood calcium) in two ways:

  1. The first is easiest to understand. Occasionally certain cancers will spread from their site of origin to other parts of the body. Some cancers (all those listed above) have a propensity to spread to the bone. This is called metastasis. When the metastatic cancer spreads to the bones it grows there and slowly eats away at the center of the bone, this releases calcium into the blood.
  2. The second way that some cancers can increase your blood calcium is via hormones and proteins that the tumor can secrete. One of these hormones is called “parathyroid-related-peptide”. These hormones can circulate in the blood and cause the bones to release calcium just like parathyroid hormone does.

Multiple Myeloma. Multiple myeloma is a cancer, but we write more about it here because it is the most common cancer cause of high calcium. Nearly half of all people with myeloma have hypercalcemia at some stage during their disease. Multiple myeloma is a cancer of the plasma cells (a type of white blood cell) that are found in the bone marrow. Plasma cells develop from B lymphocytes (a different type of white blood cell) and they produce antibodies that help the body fight infection (bacteria and viruses). When a plasma cell becomes malignant it will divide many times and produce many copies of itself that form tumors in the bone marrow. Over a period of years these tumor erode the inside of the bone, producing holes in the bones (called “lytic” lesions). Since the malignant cells are clones they all act exactly alike and they all produce the same antibody molecule that is secreted into the blood (this is what your doctor will measure).
Multiple myeloma is often detected during routine wellness testing where it shows up as an abnormally high amount of protein in the blood, a high calcium level, and often increased amounts of protein in the urine. To make the diagnosis your doctor will order a protein electrophoresis to be done. This test will examine the proteins in your blood to see if there is a large amount of one type of antibody present and if there is, the diagnosis of multiple myeloma is made.

About 15% of patients that we see for parathyroid disease have had protein electrophoresis test performed to make sure they don’t have multiple myeloma prior to them coming for treatment of their parathyroid disease. Remember, almost everybody with high calcium will have parathyroid disease. If your doctor does not order a protein electrophoresis on your first visit, then good for them. You are almost guaranteed to never need it and you have a good doctor.
 


3- Sarcoidosis

Sarcoidosis, or “sarcoid” for short, is a disease where the body’s immune system is over activated for unclear reasons. Sarcoid can often go many years before being detected, and is often found by accident when a chest x-ray is obtained for some other reason. Other patients can have symptoms such as cough or shortness of breath. Sarcoid often resolves spontaneously and therefore treatment is not always necessary. If a patient has symptoms the disease is usually treated with steroids. The cause of sarcoid is unknown. How sarcoid causes high calcium is not known, but is probably due to the same two ways that cancer causes increased calcium. This disease is very rare.

 


4- Excess Vitamin D Intake

Vitamin D is extremely important in helping maintain the balance of calcium in our bodies. Vitamin D has a direct effect on the intestines and encourages the intestines to absorb calcium from the food that you have eaten (this is why most milks are fortified with vitamin D). Vitamin D also has an effect on the kidneys and tells the kidneys to not let any calcium escape into the urine. Therefore, it is possible for a person to take too much vitamin D so that they absorb too much calcium from their diet and hold on to too much calcium in their kidneys, and their calcium goes high. In the real world, this does not really happen. Normal parathyroid glands won’t allow the calcium to go high.

 


5- Certain Drugs

It is possible for certain drugs that people are prescribed for high blood pressure to have an effect on the kidney in such a way that the kidney doesn’t let enough calcium escape the blood into the urine, and the excess calcium shows up as a high blood calcium test. The one drug that is typically associated with this is HCTZ (ydrochlorothiazide) which is a “water pill” used for blood pressure. If you have high blood calcium and you are on this drug your doctor will probably take you off of this medicine and then re-check your blood in a few weeks. Almost all the time this is not the problem (it is very rare) and your blood calcium will continue to be high and you will havehyperparathyroidism (like more than 98% of people do who have high blood calcium). In reality, this “excuse” for high blood calcium is way over used and is 90% BS. Be careful of letting a doctor say that your blood calcium is high because you are on this blood pressure medicine. It can happen, but it is WAY over used as the excuse. It is MUCH more common for you to have a parathyroid problem and just coincidentally be on this very common drug.  Be careful here, folks… this is a common mistake made that delays the diagnosis of parathyroid disease in at least 15% of all patients. Make sure your doctor doesn’t just “forget” about the high calcium and just blame it on this drug. That is a mistake almost all the time.

 


6- Milk-Alkali Syndrome.


Milk-Alkali Syndrome is a phenomenon that occurs when a patient has a stomach ulcer and they self treat it by taking lots of antacids and drinking lots of milk. They do this so they can get relief of the pain in their stomach due to too much acid in the stomach. They buy lots of antacids like TUMS and eat lots of them. They also find that drinking milk makes their stomach feel better. However, the antacids have lots of calcium in them, and so does the milk. Therefore these people are eating LOTS of calcium every day and if it gets absorbed into the blood then they will have high blood calcium. Here is the good news… this is so rare these days that 99.99% of doctors will never see this in their lifetimes. Why??? Because we have lots better ways of treating stomach ulcers (Zantac, Prilosec, Nexium, Tagamet, etc, etc, etc). People don’t treat ulcers with antacids like they used to. It is a common mistake for doctors to blame a patient’s high blood calcium on eating too much calcium. Calcium is the most highly regulated element in our bodies because it runs our brain. NORMAL parathyroid glands will not allow people to have high blood calcium REGARDLESS of how much calcium they eat.

 


7- Paget’s Disease of the Bone.


Paget’s disease (osteitis deformans) is a chronic skeletal disorder that often results in enlarged or deformed bones in one or more regions of the skeleton. Excessive bone breakdown and formation can result in bone, which is dense but fragile. This continued bone breakdown can be a cause of hypercalcemia (too much calcium in the bone). It is extremely uncommon for Paget’s disease to be diagnosed after a patient had a routine blood test that showed a high calcium level.

Smart Calcium Facts

  1. Calcium, the fifth most common element in the body, exists almost entirely (99%) as crystalline hydroxyapatite in bones and teeth.
  2. Calcium is used by nerve cells to propagate an impulse, and by muscle cells to contract. Humans want extremely regulated calcium levels because our brains (and entire nervous system) rely on calcium. If the calcium level in our blood is too high or too low, we get symptoms in our nervous system
  3. There are three ways that calcium is present in our blood: 1) protein-bound (45%); 2) attached to small diffusible anions such as citrate, lactate, phosphate and bicarbonate (10%); and ionized (45%).
  4. Doctors almost always measure just one type of calcium (serum calcium). This is the calcium that gets measured when a routine "calcium" level is ordered. This measures the amount of all three types of calcium present in the blood and this is the only test that is needed almost all the time.
  5. Ionized calcium is very important to measure in patients with hyperparathyroidism. Ionized calcium relates to the symptoms a patient will have with hyperparathyroidism. If your calcium is high normal then make sure your ionized calcium is measured since many people with hyperparathyroidism will have serum calcium levels that are normal, but their ionized calcium levels are high. It is the ionized calcium levels that make people feel bad!
  6. Hypercalcemia is defined as a serum calcium concentration above 10.4 mg/dL (2.6 mmol/L). A serum calcium concentration >14.0 mg/dL (>3.5 mmol/L) requires immediate therapy. Although there are many causes of hypercalcemia, primary hyperparathyroidism is the most common cause in the general population, and cancer and other non-PTH-mediated causes are most common in hospitalized patients.
  7. If you have high calcium, then the odds of you having hyperparathyroidism as the cause of your high calcium is about 99.9%. The odds of one of the other problems (like cancer) listed above being the cause of your high calcium is near zero.
Parathyroid Hormone Related Peptide (PTHrp) is not a perfect test to determine who's high calcium is due to cancer and who's is not. About 3% of normal people will have a high PTHrp and, 8% of people with hyperparathyroidism will have a high level. On the flip side, 12% of people with hypercalcemia due to cancer will have normal PTHrp levels (it should be high).
 
 
 
 
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