Parathyroid Problems

Hyperparathyroidism

In some people, for reasons not fully understood, one (or more) of the four parathyroid glands become overactive. Imagine an engine with the throttle running high all the time or a thermostat that won’t shut off even though the temperature has reached the set point. In this case, the one overactive gland is always producing PTH (parathyroid hormone), no matter what the blood calcium level is. The body responds by raising the blood calcium level abnormally high. In most cases, the calcium level will be just a little higher than normal, in the low or high 10s or even above 11. This level of calcium may not alter how you feel, but can cause problems. It makes some people experience fatigue, mild depression, and high blood pressure that is difficult to treat. Your bowel function may slow down, causing constipation. Over time, the calcium can build up in the kidneys and form kidney stones. Over a period of years, the buildup of calcium can clog up the filtration system of the kidneys, causing progressive failure of the kidneys. The continuous withdrawal of calcium from the bones can weaken them. In women who already suffer from osteoporosis or osteopenia, this situation just makes matters worse. If left untreated for years, the bones can become very abnormal to the point that there are obvious changes that can be seen with x-rays. This problem can occur in men also, but it is not as common since underlying bone weakness is less common in men.

In the past, patients with this disease, known as hyperparathyroidism, would not be diagnosed until these later stages of the disease, once the damage to the bones and kidneys had already been done. But now, calcium levels in the blood can be checked routinely with a simple blood test. If your calcium level is above normal, it is fairly simple to identify the cause. There are other reasons why your calcium level might be high, but a simple evaluation should make the diagnosis clear. If the high calcium level is because of an overactive parathyroid gland, a simple measurement of the PTH level will show a high PTH level, at the same time that the calcium level is high. If all the parathyroid glands are all functioning normally, the PTH level should not be elevated when your calcium level is high.

Symptoms

Although some patients may have no symptoms when their calcium level is high, most patients do have at least some of these problems, shown listed below.

• Loss of energy. Don’t feel like doing much. Tired all the time.
• Just don’t feel well; don’t quite feel normal. Hard to explain but just feel kind of bad.
• Feel old. Don’t have the interest in things that you used to.
• Can’t concentrate, or can’t keep your concentration like in the past.
• Depression.
• Osteoporosis and osteopenia.
• Bones hurt; typically it’s bones in the legs and arms but can be most bones.
• Don’t sleep like you used to. Wake up in middle of the night. Trouble getting to sleep.
• Tired during the day and frequently feel like you want a nap.
• Irritability, or “crankiness”.
• Forget simple things that you used to remember very easily.
• Gastric acid reflux; heartburn; GERD (gastroesophageal reflux disease).
• A decrease in sex drive.
• Thinning hair (predominately in older females).
• Kidney Stones.
• High Blood Pressure (sometimes mild, sometimes quite severe; up and down a lot).
• Recurrent Headaches.
• Heart Palpitations (arrhythmias).

Now, if you have some, many, or all of these symptoms and your calcium level is high, there is a good chance that you will have improvement or complete relief from some or all of them. However, there is no way to guarantee, in advance, that a correction of your high calcium level will relieve such symptoms.

There are patients who have a dramatic improvement in such symptoms, even in the first few days after surgery.

Diagnosis

The diagnosis of hyperparathyroidism is actually almost always quite simple these days, compared to 30 or 40 years ago. Unfortunately, not all physicians are completely up-to-date on the simplicity of the diagnosis with current tests.

Thirty or 40 years ago, the “intact PTH” assay was not available. Although there were some indirect tests to measure the parathyroid hormone level, they were not as specific and sensitive for identifying the problem. As a result, in those days, figuring out the cause for hypercalcemia required testing for many other possible explanations. If all of those explanations were ruled out, then hyperparathyroidism was diagnosed as the last possible explanation.

With the availability of the “intact PTH” assay, it is much easier to confirm that the parathyroid glands are the problem. If your calcium level is high, 10.3 mg/dl or higher and if you are generally healthy, then the next test to order is intact PTH level with another corresponding calcium level. If the calcium remains high, and the intact PTH is also high, or even just in the high normal range, then you definitely have hyperparathyroidism. If the calcium is high for any other reason, the intact PTH level will be low.

Most physicians know about ordering the intact PTH level these days. But many physicians still think they must still order all of the other tests that we used to do, back when the intact PTH assay was not available. These other tests, rarely necessary anymore, include serum protein electrophoresis (SPEP), 24-hour urinary calcium collection, serum markers for cancer antigens, x-rays, discontinuation of certain diuretic blood pressure medicines, vitamin D levels, among others. If your physician is ordering some or all of these other tests, you may want to question him about this. In most cases, it is a waste of money, time, and resources. Now, there are certain cases when the test results are borderline, for instance, if your calcium level is just slightly elevated, or if your PTH level is in the midrange, when some of these other tests may be appropriate still. And in these cases, it might be more difficult to determine whether there is a problem with your parathyroid glands or not. But these situations are much less common.

Another situation we see very commonly has to do with a previously known high calcium level. Some physicians will note that your calcium is high, but will say “let’s just watch this for now”. And they might not check it for another 6 or 12 months. This may go on for a few years before anyone identifies that there is a parathyroid gland problem. I would strongly recommend that if you have a calcium level above 10.3 mg/dl, that you have an intact PTH level drawn. If it is high, then you almost definitely have a parathyroid problem, and in most cases this is just a single gland problem, which can be easily removed, immediately curing the high calcium level. Even if there is more than one gland that’s abnormal, a curative surgical procedure brings the calcium level right back down to normal.

Now if you already have both a high calcium level and intact PTH level, no other tests are needed to make the diagnosis. You have hyperparathyroidism. Many physicians will still feel the need to order additional tests, such as a sestamibi scan, but this test is not at all necessary in order to know that you have the disease. The sestamibi scan is extremely helpful in planning the surgery and there usually is no need for the sestamibi scan except for in the setting of a planned surgical procedure. If you have not yet had a sestamibi scan, there is no need for this to be done prior to seeing a surgeon about the operation.

Vitamin D and Calcium

Increasing attention has been given to measuring vitamin D levels in patients over the past few years. One reason for this is that the test has become easier and cheaper to order. Another reason is that endocrinologists and others have been finding low levels in a higher percentage of patients. There is a definite connection between calcium and vitamin D levels, and so it’s not surprising that vitamin D is thought about in patients with hypercalcemia.

The metabolism of vitamin D is very interesting and very complex. We still don’t understand all of the intricacies of what the human body does with this protein, and what all of its functions are. But we do know a lot about the basics. The main effect of vitamin D is to affect the level of calcium and phosphate in the bloodstream. It does this by stimulating the intestines to increase the absorption of calcium and phosphate and decreasing the excretion of calcium and phosphate from the kidneys. If vitamin D levels are low, the parathyroid glands are stimulated to produce more of their hormone (PTH). But remember that the parathyroids also are regulated by the calcium level in the bloodstream.

Vitamins are named as such because in general, the human body is unable to do without these substances, and they must be provided in the diet (or, in the case of vitamin D, through another external effect). As it turns out, our skin can produce the precursor to active vitamin D when exposed to the sun. Just 10-15 minutes of sunlight each day will allow production of the daily vitamin D requirements. If there is no exposure to sunlight, then the body must obtain its vitamin D requirements from what we eat.

Now you probably know that for years, doctors have strongly discouraged spending time in the sun, because it increases the risk for skin cancer and sunblock is considered a must for all “sun worshippers” these days. But if you stay out of the sun, or use sunblock religiously, then your body might not get its vitamin D needs through this source. And so, by discouraging sun exposure, we have substituted one problem, low vitamin D levels, for another, higher skin cancer risk. This is probably a good tradeoff since vitamin D can be provided through your diet as well, but this recommendation (avoiding sun exposure) probably is the reason we are seeing more patients these days with low vitamin D levels.

So what does all this have to do with hypercalcemia and hyperparathyroidism? Well, since a low vitamin D level can cause an increase in the intact PTH level, many endocrinologists will wonder whether the low vitamin D level is the culprit when someone is diagnosed with hyperparathyroidism. BUT, if the calcium level is HIGH, then the low vitamin D level is NOT the cause of the high PTH level. If a person has NORMAL parathyroid glands, and a low vitamin D level, (which then stimulates higher PTH levels), the calcium level will NOT go above normal levels. It will stay in the normal range. Even though the low vitamin D level stimulates PTH production, an increased calcium level will simultaneously inhibit the PTH production to a greater extent. So the calcium level will never get above the normal range under these circumstances.

Now, this can get confusing very easily, and I would say that probably many physicians do not really understand this either. But the bottom line is if you are generally healthy and you have a high calcium and a high PTH, then you have a parathyroid problem, no matter what your vitamin D level is. If you have a NORMAL calcium AND a slightly high PTH, then the problem could be EITHER a vitamin D deficiency or a parathyroid problem. If you have a low calcium and a high PTH level, then you have either a calcium or vitamin D deficiency in your diet.

So once again, if you have a HIGH calcium, and a high or high-normal PTH level, you probably have hyperparathyroidism If your doctor checks your vitamin D level (specifically the 25 OH-vitamin D) and it is LOW, it is probably BECAUSE of the hyperparathyroidism, and not the cause.

Tests

Sestamibi Scan

This test is named after the radioisotope used. It is the same radioisotope used for patients undergoing evaluation of their heart function. It works in both tests for the same reason—the isotope is taken up after injection into the bloodstream by the most metabolically active cells in the body. These cells are using large amounts of energy constantly. Less active cells do not take up much of the radioisotope. As a result, the scan that is taken shows focal areas or “hot spots” that show where the most active cells are. In the case of parathyroid glands, a single adenoma almost always shows as a “hot spot” on the scan, since it is a “high energy” gland. In most cases, the other glands are in a resting state and will not show up. Now as we have gained experience with parathyroid surgery and interpretation of sestamibi scans, we know that sometimes a second gland will also be overactive and might not show up on the sestamibi scan. It seems that if there is more than one overactive gland, only the most active gland might “light up”. This important detail explains why some patients have unsuccessful procedures. If a surgeon does not recognize this possibility, and only finds and removes a single gland based on a “positive” sestamibi scan, there might be another slightly less active but still overactive parathyroid gland remain behind. In this case, the calcium level is either going to remain high or return to a higher level on down the Road.

It is important to remember that the sestamibi scan is not intended to be used to decide if you have hyperparathyroidism or not. It does help to determine which gland or glands are the problem and is extremely useful when done at the time of your surgery. But if your physician has ordered a sestamibi scan, and you’re not scheduled for surgery at the same time, you should ask why this is being done. If you have a high calcium and high intact PTH level, then you definitely have a parathyroid problem. In this situation, there is no point in doing a sestamibi scan outside of the context of planning a parathyroid operation.

The sestamibi scan is not a perfect test. Sometimes it is “negative”, meaning that it does not show evidence of an overactive parathyroid gland when there actually is one. Sometimes it may show a single overactive gland when actually more than one is overactive. So the interpretation of the test requires some experience and judgment.

Ultrasound

Another useful test for localizing a parathyroid adenoma is an ultrasound. This test uses the same technology as is used in pregnancy to look at the fetus in the womb. The ultrasound probe is placed on the neck, which shows the internal anatomy. Normal parathyroid glands are so small that they will not be identified with ultrasound. But the overactive glands will often be large enough to be seen, as a distinctive dark, somewhat triangular shaped structure, just behind the thyroid gland. This test can be helpful in knowing before the operation what the size of the abnormal gland is, but it does not provide the same information as the sestamibi scan, which correlates more closely with overactivity in an individual gland. An ultrasound is also helpful to know if there is anything abnormal in the thyroid gland. If there is any abnormality in the thyroid, it is best to know this in advance.

Just as with the sestamibi scan, the ultrasound test is not necessary to make a diagnosis of hyperparathyroidism. But it can be very useful in planning the surgery. I typically do the ultrasound scan myself at the time of the initial consultation. In about two-thirds of the cases, I can see a single enlarged parathyroid gland, which almost always correlates with the sestamibi scan. Many ultrasound technicians do not have much experience looking for abnormal parathyroid glands. Ultrasound studies of the neck are almost always evaluating either the thyroid or the blood vessels in the neck, and not the parathyroids, and so the technologist’s experience with the parathyroid disease is limited. And unfortunately, the radiologist does not do the scan themselves; they only look at the images that the technician takes. So their interpretation of the ultrasound may likewise be limited.

CT Scan

The 2 tests discussed above, the sestamibi scan, and the ultrasound, are the most important ones in evaluating the parathyroid glands. But the CAT scan and the other tests listed below can sometimes be useful. The CAT scan is not usually necessary in the initial diagnosis of hyperparathyroidism. Sometimes, a CAT scan is ordered to evaluate for some other problem, and an abnormality may be seen in the thyroid gland or possibly a parathyroid gland. It will be very uncommon to identify a hyperparathyroid problem in this sequence. There is also a special type of CAT scan discussed further below called CT angiography.

It is probably sufficient to say that the CAT scan is rarely necessary to diagnose or treat hyperparathyroidism.

SPECT

SPECT standards for “single photon emission computed tomography”. It has similarities to the sestamibi scan described above. But rather than being a picture taken in 2 dimensions, the camera, which measures gamma radiation, is rotated around the patient, and then a computer can make three-dimensional images. It sounds like it might be better than just the “plain old” sestamibi scan, but as it turns out, the sestamibi scan, in conjunction with surgery on the same day, is usually quite sufficient. At some centers, all patients are sent for a SPECT study, but in my opinion, this is rarely necessary. The images are similar to what we get with a CAT scan, except the resolution is very low, meaning that the images are very “fuzzy”. For this reason, they are not as useful as one might think.

Arteriography

Some facilities have become enamored with doing arteriography to look for enlarged parathyroid glands. Sometimes this is combined with a CAT scan called CT angiography. This test can be quite good at identifying an enlarged parathyroid gland. However, it is rarely necessary. Endocrinologists often order it, it in the interest of knowing which parathyroid gland is abnormal, or if possibly all 4 are involved in the process. Now when it comes to doing the surgery, this information is critical, but the abnormal gland can usually be identified using the sestamibi scan, which is done just before the surgery. Intraoperative hormone levels of PTH can also be measured, to confirm that the abnormal gland has been removed. For these reasons, doing a test prior to the surgery to try to find the abnormal gland is somewhat redundant. In addition, this test is “invasive,” and quite expensive. So in most cases, it really is not necessary.

In the small number of cases in which someone has already had an unsuccessful parathyroid operation, tests such as this are much more commonly and appropriately ordered.

Venous Sampling

There is another sophisticated test that involves placing a tiny catheter into a vein in your groin and then advancing the catheter through the vein up into the neck veins. The catheter tip position can be seen on x-ray. Samples of blood are drawn from several different locations within the neck veins, and the intact PTH level is measured in each of these. By comparing the different levels from the different locations, one can deduce where the excessive PTH level is coming from, and therefore, which parathyroid gland is overactive. Although this test is usually very accurate, it is more complicated and much more expensive than the sestamibi scan and ultrasound. So if the abnormal gland can be identified with these simpler tests, this venous sampling is not often necessary. But in very unusual circumstances, this test might be considered.

Treatment

Since the high calcium level is detrimental to the body’s system over time, it is usually recommended to fix the problem. Currently, there are no medications to correct it, but the abnormal parathyroid gland can easily be removed surgically, providing an immediate cure. In most cases, the problem is limited to just one of the four glands. Nothing needs to be done to the normal glands.

Surgery

For the past hundred years, the surgical treatment for hyperparathyroidism involved making a long neck incision under general anesthesia and searching all the nooks and crevices in the neck around (and even inside) the thyroid gland, for all four parathyroid glands. The surgeon would then make a visual assessment of the four glands, to decide which one, or more, of the glands, looked “too big”, and presumably overactive. Biopsies of one or more of the glands would be done, to try to decide which glands to completely remove. In some cases, not all of the glands would be found, and in fact, it might be that the abnormal gland may never be identified. Up until about the 1980’s, the surgeon had no information prior to the surgery as to what he may find, and for this reason, a very long incision was used, and the “exploration” of the neck was extensive, tedious, and time-consuming.

The search for helpful pre-operative tests eventually identified the sestamibi scan, and the ultrasound, as being very helpful for providing a roadmap for the operation.

The sestamibi scan is named after the radioisotope used. It is the same radioisotope used for patients undergoing evaluation of their heart function. It works in both tests for the same reason — the isotope is taken up after injection into the bloodstream by the most metabolically active cells in the body. These cells are using large amounts of energy constantly. Less active cells do not take up much of the radioisotope. As a result, the scan that is taken shows focal areas or “hot spots” that show where the most active cells are. In the case of parathyroid glands, a single adenoma almost always shows as a “hot spot” on the scan, since it is a “high energy” gland. The other glands, which are in a resting state, will not show up. As a result, the scan can identify a single gland that is overactive. In most cases, if only a single “hot” gland is seen on the scan, then the other glands are usually (but not always) normal.

As more experience was gained with the sestamibi scan, it was thought that if this test was “positive”, showing a single enlarged gland, then a surgeon wouldn’t necessarily have to find all the other glands to achieve success in most cases. This was the original basis for the less invasive procedure, called a MIRP, or “minimally invasive radio-guided parathyroidectomy.” But with further experience, less reliance has been given to a sestamibi scan that shows a single “hot” gland. It is not uncommon for there to be another parathyroid gland besides the “hot” one, that is also overactive. So the sestamibi scan can give guidance regarding the most overactive gland, but it does not eliminate the possibility that another overactive gland is present. It is this understanding that has led us to evolve to a minimally invasive procedure that incorporates the identification of all four glands if possible. This is done regardless of what the sestamibi scan shows.

Another useful test for localizing a parathyroid adenoma is an ultrasound. This test uses the same technology as is used in pregnancy to look at the fetus in the womb. The ultrasound probe is placed on the neck, which shows the internal anatomy. Normal parathyroid glands are so small that they will not be identified with ultrasound. But the overactive glands will usually be large enough to be seen, as a distinctive dark, somewhat triangular shaped structure, just behind the thyroid gland. This test can be helpful in knowing before the operation what the size of the abnormal gland is, but it does not provide the same information as the sestamibi scan, which correlates more closely with overactivity in an individual gland. An ultrasound is also helpful to know if there is anything abnormal in the thyroid gland. If there is any abnormality in the thyroid, it is helpful to know this in advance.

MIRP (Minimally Invasive Parathyroidectomy)

These new tests have given birth to a less invasive surgical cure for hyperparathyroidism, the MIRP, or “minimally invasive radio-guided parathyroidectomy.” It’s important to know that this term is used differently by different surgeons, as newer variations have evolved since it was first described.

With this technique as originally described, a small incision about one inch in length is used. A sestamibi scan is done immediately before the surgery so that the abnormal glands have the high concentration of sestamibi in them during the surgical procedure. With this technique, the surgical dissection is very focused and limited. The normal glands are left alone. As a result, the operation is usually completed in 30-60 minutes and can be done without general anesthesia if desired. Patients can go home the same day.

As surgeons began using this minimally invasive technique, it was understood that there is no technique which will be successful 100% of the time. Historically, if a surgeon was successful about 90% or more of the time, this was considered about as good as one could get with the traditional big incision “neck exploration.” As the minimally invasive procedures started to be done, this success rate of 90-95% was considered the target to match.

It became evident that there were ways to further increase the success rate, in the context of the minimally invasive procedure or MIRP. Although the initial MIRP procedures focused on making a small incision and limiting the dissection, surgeons would occasionally want to look at one or more of the other parathyroid glands. But since a primary goal had been to keep the incision small, some surgeons, including surgeons at DeKalb Surgical Associates, began to get increasing experience with identifying the other glands, but still, keep the incision small. Now it is not something easily learned to find all four parathyroid glands through a small incision, but this is possible for those surgeons with a concentrated experience gained only through having performed a high volume of MIRPs.

With this increasing experience of identifying all four glands through a small incision and realizing that occasionally the sestamibi scan will show a single “hot” gland when there is also a second overactive gland, some surgeons began making it a policy to routinely look for all four glands, very similar to the old-fashioned long incision “neck exploration.” Now, the sestamibi scan and ultrasound provide a pre-op roadmap and with the increased surgical experience, the success rate of the procedure has come closer to 100%. In a sense we’ve come almost full circle in parathyroid surgery, but with marked improvements in technique and in outcomes. No longer does the operation take 4 hours and require a Frankenstein incision. No longer do we have only visual feedback based on gland size to determine which glands are abnormal. No longer must patients be hospitalized after the operation.

I still consider this most recent evolution of the MIRP to be a minimally invasive procedure, since it is still done through a small incision, and as an outpatient, with minimal complications. But in most cases, all four glands can be identified which decreases the possibility of missing a second overactive gland. There are many surgeons who are only now starting their experience with MIRPs, based on the first methods used, of trying to know in advance of the surgery which gland should be removed, and only finding and removing that one. They may have a reasonable success rate, but will most certainly have patients with second adenomas which are only “discovered” when the serum calcium fails to normalize after the operation.

One significant thing we make sure to identify when the sestamibi scan is complete is that there are no parathyroid adenomas in unusual locations, such as up high in the neck, or down low in the chest. Though uncommon, if you have an overactive parathyroid gland in one of these locations, the usual neck incision is not going to cure you.

If you have had a sestamibi scan done already and it was read as “negative”, you can still have minimally invasive surgery. One very good thing about a negative sestamibi scan is that it rules out the possibility that you have a gland somewhere outside the usual locations. This is actually very helpful for your surgeon even though you might have been told that you are not eligible for minimally invasive surgery. That simply is not true. In other words, seeing that there are no “hot spots” in either normal OR abnormal places means that even if not seen on the scan, they must be hiding in the usual positions behind your thyroid, where we can find them with the usual dissection.

Complications during the procedure are very uncommon, but you should be aware of these possible problems. Behind the thyroid, on either side is a nerve that activates each vocal cord in your larynx (voice box). These nerves are quite close to the parathyroid glands so it is possible for them to be injured during the surgery. If this happens, your voice is likely to be affected. With the traditional parathyroid surgery, there is a lot of dissection done very close to both of these nerves. Fortunately, even with the traditional operation, injuries to these nerves (recurrent laryngeal nerves) are uncommon. But with the MIRP, even less dissection required. This focused procedure, which is usually almost bloodless, does not require dissecting the nerves, thus minimizing the risk of any injury or bruising. Excessive bleeding is a potential complication of any surgery, no matter how small or large the operation is. This problem is only very rarely seen with the MIRP since the dissection is limited to finding only the involved parathyroid gland.