Diagnosis of Hyperparathyroidism and

Tests used for the Diagnosis

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Diagnosis of the problem

Vitamin D and Calcium

Tests Used to Diagnose Hyperparathyroidism



CT Scan



Venous Sampling


   Diagnosis of the problem

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. As a result, 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 in 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.

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, discussed below. 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, but it is not at all necessary to know that you have hyperparathyroidism. There usually is no need for the sestamibi scan except for in the setting of the planned surgical procedure. This will be discussed more below. But 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.

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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 blood stream.  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 blood stream.

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 “sunworshippers” 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 increasing 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.

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Tests used to Diagnose Hyperparathyroidism

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.  The other glands, which are in a resting state, will not show up.  As a result, the scan can identify the single gland that is overactive.  The surgery can then be directed toward identification and removal of a single gland.  This is the basis for the less invasive procedure, called a MIRP, or “minimally invasive radioguided parathyroidectomy”.


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 is 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.

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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 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.

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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.


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

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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.

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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 appropriately ordered.

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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 that 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.

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DeKalb Surgical Associates
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Decatur, Georgia 30033 (a suburb of Atlanta)

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