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Primary Hyperparathyroidism

What is it?

As mentioned in the previous section, the parathyroid glands produce parathyroid hormone which regulated the body’s calcium level. Specifically, when the blood levels of calcium are low, the parathyroid glands detect this and release parathyroid hormone into the blood. This serves to increase blood calcium levels via mechanisms explained earlier. Once the blood calcium levels are normalized, the parathyroid glands are supposed to decrease production of parathyroid hormone to halt further increases in calcium.

Hyperparathyroidism is a disease in which the parathyroid glands do not shut off when they are supposed to. In other words, once the blood calcium has reached the appropriate level, instead of stopping production of parathyroid hormone, the parathyroid gland continues produce it resulting in abnormally high levels. This is called hyperparathyroidism (hyper = too much).

There can be several causes of hyperparathyroidism, but one of the most common causes is enlargement of one of the glands, usually due to a tumor. Do not be alarmed, however! A tumor does not always necessarily mean cancer (in fact, tumor is the latin derivation of ‘tumere’ which simply means ‘to swell’). This enlargement in size of one of the glands results in an overproduction of parathyroid hormone, and abnormally high levels of calcium in the blood. In response, the other three normal glands apprpriately shut down parathyroid hormone production and become smaller. As we mentioned, although there may be a tumor in overactive parathyroid gland, it is almost never cancerous (less than a 1 in 1000 chance) (Verify). However, the chronically high levels of calcium can cause damage to the body in many other ways by slowly destroying tissues.

Unfortunately, these tumors (also known as adenomas) start from one out-of-control cell that continues to multiply and increase in size until it is removed. Oftentimes, they can become as large as an a grape or even a walnut. As the adenoma grows, it secretes more and more parathyroid hormone unregulated, which continues to increase blood calcium levels and make you feel progressively worse. Again, the only true cure for this is removal of the adenoma while leaving the other, normal glands intact.

Most patients with a parathyroid adenoma will have abnormally high parathyroid hormone (PTH) and calcium levels. A normal PTH level is under 60, and patients with a parathyroid adenoma will usually have levels between 60 and 150. Occasionally, someone may have a calcium level that is high, but a PTH level that is within normal range. This is called an ‘inappropriately normal’ level of PTH, because the PTH level should actually be low when the calcium level is high. A normal PTH level with a high calcium level is abnormal.

About 10% of the time, a patient with a hyperparathyroidism will have two parathyroid adenomas instead of one. And very rarely, about 3% of the time, a patient with hypoparathyroidism will have enlargement of all four parathyroid glands. This is called parathyroid hyperplasia.

Risk Factors

Age
Hyperparathyroidism is most common in patients in their 50s, 60s, and 70s. However, this does not mean that younger individuals cannot develop parathyroid adenomas. The average age for parathyroid adenomas is 59 with the most common age being 62. Again, most patients are between 40 and 75, but both younger and older patients are at risk.

Although rare, younger patients with high calcium will often present after some type of event like a kidney stone, broken bones, headaches, or high blood pressure. The doctor will run blood tests which show high calcium and then proceed to investigate the cause of this. Although the doctor will not suspect hyperparathyroidism in an individual at such a young age, the right blood tests will make the diagnois easy. And even in younger individuals, the vast majority of patients will only have one bad parathyroid gland, just like the older population.

Genetics
There are certain genetic conditions such at the MEN (multiple endocrine neoplasia) syndromes that can predispose a person to developing a parathyroid adenoma, even at a very young age (under 20). Unlike other causes of parathyroid disease, most people with this condition will develop 4-gland hyperplasia, not a single adenoma. People with MEN will most often show up as a teenager with kidney stones due to excess calcium. If you are known to have this genetic condition, or know of a family member who has this condition, your blood PTH levels should be monitored on a regular basis.

Medications
There are certain medications such as lithium which can increase your risk of developing a parathyroid adenoma if taken for prolonged periods of time (over 10 years). Fortunately, lithium is a very old psychiatric drug and not often used, so the percentage of parathyroid patients that we see using it is very small. These patients do have a slightly higher risk of having tumors in multiple parathyroid glands when compared to other patients with parathyroid disease, so all 4 glands must be carefully assessed.

Previous radioactive iodine therapy for thyroid problems
Even though the parathyroid and thyroid glands are unrelated in function, they are very close to each other and share the same blood supply. In patients with overactive thyroids, oftentimes the treatment is radioactive iodine to kill the thyroid gland. A very small percentage of patients who have had radioactive iodine therapy for treatment of their thyroid disease can develop parathyroid problems down the road. Usually this happens an average of 25 years after radioactive iodine therapy but occasionally can be seen earlier. But again, just like in other cases, these patients usually develop a single parathyroid adenoma and not multiple gland hyperplasia.

Face or neck radiation
Back in the 1940s, 50s, and 60s, radiation was used as a treatment for several things including acne and swollen glands. At the time it was not know that this could increase the risk of developing thyroid cancer as well as parathyroid adenomas. Again, the time it takes to develop parathyroid disease after undergoing radiation is decades, with the average being 30 years. Most people develop a single adenoma, although there is a higher risk of developing multiple adenomas or 4 gland hyperplasia. Just a reminder, these parathyroid adenomas are NOT cancerous.

Symptoms

When parathyroid disease was first described in the 1920s, the symptoms were known as ‘moans, groans, stones, and bones… with psychic overtones.’ Although that sounds quite scary, with the advent of better technology and more routine blood testing in today’s modern medical world, most patients do not get this far along in their disease. In fact, although some patients with parathyroid disease claim they do not have symptoms, almost all of them will claim they feel better once the problem is fixed. This happens because parathyroid tumors develop very gradually over time and so patients feel progressively worse, but cannot remember how they felt before and just accept it as their new reality. Symptoms can be very obvious – such as kidney stones, frequent headaches, and depression. However, they can also be very subtle, like high blood pressure and the inability to concentrate. Here is a list of the most common symptoms of parathyroid disease:

Lack of energy or chronic fatigue
This is the most common symptom of hyperparathyroidism, with up to 80% of patients reporting it as their primary problem. People describe feeling ‘tired all the time,’ or ‘running out of energy by early afternoon.’ This makes sense when we consider that the nervous system depends on calcium for conducting signals, and as the day wears on the body’s calcium levels get lower and lower, leading to feelings of tiredness, fatigue, and poor memory.

Feeling generally ‘bad’ but unable to pinpoint why losing interest in activities you once enjoyed unable to concentrate.

Depression
This is also a very common symptom of hyperparathyroidism. As many is 50% of patients will report they were placed on an antidepressant within the last year. Symptoms of depression can vary widely but usually include disturbances or changes in sleep, interest in activities, feelings of guilt, lack of energy, inability to concentrate, change in appetite (eating too much or too little), feelings of fatigue or restlessness, and thoughts of suicide. If you are feeling any of these symptoms, especially the last one, you should see a doctor immediately.

Bone pain, osteoporosis or osteopenia
As discussed earlier, chronically high levels of PTH cause the body to continually pull calcium from the bones making them weak. This can lead to bone pain. However, if this continues to go on for a long time unchecked, the bones can actually become brittle and break. This is called osteoporosis or osteopenia depending on how brittle the bones are. A simple test called a DEXA scan can measure the density of the bones in your body and compare it to what would be normal for someone your age. Based on this number you may be classified as osteopenic (which means you are 1 to 2.5 standard deviations below what you should be) or osteoporotic (meaning you are more than 2.5 standard deviations below what you should be). Without going into too much detail, it is sufficient to know that osteopenia can lead to osteoporosis as the bone loses more and more calcium and becomes weak.

Difficulty Sleeping

Irritability

Forgetfulness

Gastric acid reflux (heartburn) or GERD
About half of parathyroid patients describe having acid reflux , or gastroesophogeal reflux disease (GERD). This is because high calcium levels cause an increase in acid production in the stomach, which is the source of heartburn. If this goes unchecked, it can lead to an ulcer in the stomach or esophagus (the food pipe that leads to the stomach), which can eventually bleed and require emergency surgery. Thankfully, once the parathyroid disease is cured, this problem goes away on its own within 1-2 weeks and patients can stop taking their acid reflux medicine.

Decreased sex drive

Thinning of hair

Kidney stones

High blood pressure that goes up and down a lot

Recurrent headaches

Heart arrhythmias (palpitations)

Because the symptoms can be so gradual and subtle, it is oftentimes a family member who detects a change in personality over several years. Things such as more crankiness, shorter temper, or emotional lability are often reported by a spouse even though the patient themselves may not be aware of it.

It is important to note that the severity of the symptoms is NOT related to the level of calcium. In other words, higher calcium levels do not mean your symptoms are worse. There are people with extremely high calcium levels that only have mild symptoms, and people with only slightly elevated calcium levels that can have terrible symptoms. If your calcium is only borderline elevated but you feel like you have the above symptoms, have your parathyroid levels checked!

Potential other health issues

There are some other potential, health issues that can be related to parathyroid disease, some fairly common and some uncommon

Osteoporosis
Because hyperparathyroidism causes high levels of calcium to be absorbed from our bones, it can cause them to become fragile and susceptible to fractures and breaks. This happens in almost all patients who have long-standing parathyroid disease, but it is reversible! Unfortunately, if parathyroid disease goes untreated, the risk of bone fracture can increase by 10-25 times. It is important to note that the drugs typically used to treat osteoporosis in other patients (such as older women with low estrogen) do not work in patients with parathyroid disease. Thankfully, however, the osteoporosis is nearly always reversible once the parathyroid disease is treated. A test called a ‘DEXA scan’ will allow your doctor to measure the density of your bones and determine whether or not you may have osteoporosis.

Low Vitamin D levels
Vitamin D is used in our intestines to help the body absorb calcium from the food we eat. Most of the Vitamin D in our body comes either from our diet or is synthesized in our skin cells with the help of sunlight. Without Vitamin D, our body would not be able to absorb the calcium we ate, no matter how much we took in. That’s why food with lots of calcium, such as milk, is often fortified with Vitamin D.

So as you can see, if a patient has hyperparathyroidism and high calcium levels, the body will naturally want to decrease its levels of Vitamin D. Lower Vitamin D levels will decrease the amount of calcium absorbed from the intestines and thus prevent the body’s calcium levels from rising even higher. This is why 2/3 of all patients with hyperparathyroidism will have low Vitamin D levels. But the low Vitamin D levels are certainly not the cause of the parathyroid disease. If this was the case, the PTH levels would be high while the calcium levels would be LOW. Most patients with parathyroid disease have HIGH calcium levels, and high or normal PTH values.

Other causes of high blood Calcium

Although over 99% of people with high blood calcium will have a parathyroid problem, there are some other rare causes of high calcium in the blood, which can cause symptoms similar to those of parathyroid disease.

Cancer
There are certain rare cancers that have been associated with high calcium levels. These include multiple myeloma (a cancer of the immune cells), certain lung cancers, breast cancer, kidney cancer, and squamous cell cancer of the head and neck. Of these, multiple myeloma is the most common and can be diagnosed by your physician using a simple blood test. But remember, less than 0.01% of people with high calcium in the general population have cancer and the overwhelming odds are still in favor of curable parathyroid disease.

Sarcoidosis
Sarcoidosis is an overactivity of the body’s immune system that can cause masses to develop in the lungs, and through unknown mechanisms results in high calcium. Again, this is rare but treatable with steroids.

Excess Vitamin D
As we discussed earlier, the body needs Vitamin D to absorb calcium from the intestines. So, as you can imagine, consuming large amounts of Vitamin D can cause the body to absorb excess calcium. In reality, however, this is extremely rare and a person would have to take in huge amounts of vitamins per day AND have an overactive parathyroid gland for this to happen.