Once the diagnosis of primary hyperparathyroidism has been established from the calcium and PTH levels, and a decision for surgery is made, the next step is usually to determine what additional information should be obtained in order to assure a successful operation.

This is where imaging becomes useful.

It is worth repeating the central point from Part One: imaging does not make the diagnosis. Imaging is performed after the diagnosis has been made to help the surgeon decide where the abnormal gland is likely to be and how best to approach the operation. Even patients with negative imaging remain candidates for surgery if the biochemical diagnosis is clear.

There are several different imaging studies available, and they do not all provide the same information.

1. The sestamibi scan

The sestamibi scan has been one of the most commonly used parathyroid localization studies for many years.

A small amount of radioactive material is injected into the bloodstream. Hyperfunctioning parathyroid tissue often takes up and retains more of the sestamibi than the surrounding tissues. Images are then obtained to look for an area of increased activity.

When the scan shows one convincing focus, it provides useful evidence that a particular gland is hyperfunctioning.

But there are limitations.

A positive sestamibi scan does not prove that the other three glands are normal. It simply tells us that one gland accumulated enough tracer to be seen.

And a negative sestamibi scan does not mean that the patient does not have hyperparathyroidism. It means only that the scan did not localize the abnormal gland. Sestamibi is also less reliable when more than one gland is abnormal.

This distinction is extremely important because I have seen patients whose diagnosis was questioned simply because their sestamibi scan was negative. If the calcium and PTH establish primary hyperparathyroidism, a negative scan does not undo that diagnosis.

If the sestamibi scan is performed immediately before surgery, there can be an additional benefit. The injected sestamibi is still present in the tissues during the operation, allowing the surgeon to use a handheld gamma probe to measure radioactivity. Hyperfunctioning parathyroid tissue usually retains more sestamibi than surrounding tissues, which can help locate an abnormal gland. Once tissue is removed, its radioactivity can also be measured immediately and can provide another clue that the specimen is parathyroid tissue, without waiting for a frozen-section pathology report. I will discuss this technique in more detail later in this series.

2. Ultrasound of the neck

Ultrasound looks at the problem differently.

Rather than measuring the uptake of a radioactive tracer, ultrasound looks directly at the anatomy of the neck. An enlarged parathyroid gland often has a characteristic appearance and may be seen behind or adjacent to the thyroid gland. Normal or dormant glands are rarely seen on ultrasound because they blend in with the other surrounding soft tissues.

Ultrasound has several advantages. There is no radiation, it is relatively inexpensive, and it also gives us useful information about the thyroid gland.

One limitation is that ultrasound is very dependent on the person performing and interpreting the study. It can also have difficulty identifying glands that are very deep, behind the trachea or esophagus, or located somewhere unusual.

When an ultrasound and sestamibi scan both identify the same gland, that gives us considerably more confidence about where the problem is located. These studies are often complementary rather than competing tests.

3. 4D CT scanning

A 4D CT scan provides much more detailed anatomical information.

The term “4D” refers to the fact that the scan looks not only at the three-dimensional anatomy but also at how a suspected parathyroid gland takes up and releases intravenous contrast over time.

This characteristic enhancement pattern can help distinguish abnormal parathyroid tissue from lymph nodes, thyroid tissue, and other structures in the neck.

4D CT can be particularly useful when the ultrasound or sestamibi scan is negative or when the studies disagree. It can also be very helpful for glands in unusual locations. Studies have shown that 4D CT can localize glands that were not seen on traditional imaging.

The tradeoff is greater radiation exposure and the need for intravenous contrast, so it is not necessarily the first test every patient needs.

4. Choline PET imaging

A newer option is fluorocholine PET/CT. Parathyroid tissue has a high rate of cellular membrane activity and can preferentially accumulate radiolabeled choline. This can allow PET imaging to identify very small or difficult-to-localize abnormal glands.

Choline PET it is gradually assuming a greater role when more traditional studies are negative or equivocal, most often in patients who have already had an unsuccessful first operation. Published studies have reported very high localization sensitivity in selected patients. Availability and insurance coverage can be limiting, so it is not currently a routine study for most patients.

5. No imaging test is perfect

This may be the most important point in Part Two.

Every imaging study provides evidence about which gland or glands might be abnormal. None provides absolute proof.

If a sestamibi scan, ultrasound, and 4D CT all point to the same gland, we can be very confident that gland is abnormal. But that still does not prove that the other glands are functioning normally.

Conversely, if every scan is negative, that does not mean there is no abnormal gland.

If the biochemical diagnosis is correct, there is abnormal parathyroid function somewhere.

That is why I think of imaging as creating a road map for the surgeon. Sometimes the map is excellent. Sometimes it is incomplete. And occasionally it points us in the wrong direction.

Ultimately, the surgeon must combine what was learned before the operation with what is found during the operation.

That leads directly to Part Three.

Once the neck is explored, what does an abnormal parathyroid gland actually look like? Is a larger gland always the abnormal one? What does a normal gland look like? And perhaps most interestingly, what happens to the other parathyroid glands when one gland has been overproducing PTH for a long time?

In Part Three, I will discuss the visual appearance of normal, hyperfunctioning, and suppressed—or what I often call “dormant”—parathyroid glands and how those findings help guide surgical decision-making.

Disclaimer

This article is for general education only and is not personal medical advice. Individual recommendations depend on a patient’s history, laboratory findings, imaging, operative findings, and overall clinical situation.