Parathyroid Ultrasound: Facts & Myths - HD

Introduction

I am Dr. Franklin Tessler from the University of Alabama at Birmingham.
I'm going to be speaking about parathyroid ultrasound.
I have no relevant financial disclosures,
but I will say that I once binge watched Breaking Bad for an entire weekend.

Goals and Objectives

Here are my goals and objectives for this presentation.
Starting off, why do parathyroid ultrasound, what's the proper technique?
Do we see normal parathyroids and ultrasound?
What do abnormal parathyroids look like?
What else can cause parathyroid enlargement?
And do parathyroid adenomas ever arise in the thyroid gland?

Why Perform Parathyroid Ultrasound?

To understand the parathyroid story, you have to go back to this fellow Ivar Sandstrom, who was credited with the first description of the parathyroid glands in mammals.
He did this while he was a medical student in Sula Sweden, which is quite remarkable.
He noticed one day some small structures next to the thyroid gland in dogs, and being an inquisitive fellow looked at other animals and humans, and eventually described the parathyroid glands in detail.
Of course, he was interested in an academic career, so he submitted his description to a German journal, which rejected his submission and said it was too long.
He wasn't going to stand for that, so he sent the full submission to a journal in Sweden where it was published.
Unfortunately, he suffered from a familial depressive condition and committed suicide in his thirties, but he will be remembered for his contribution to discovering the parathyroid glands and describing them in subsequent years.

Physiology and Pathology of Parathyroid Glands

The central role of the parathyroid glands in calcium regulation shown on this slide was described.
The parathyroid glands are intimately involved in calcium metabolism as you see here, and also involved with vitamin D metabolism.
What we're going to talk about from a pathologic point of view or physiologic point of view is primarily hyperthyroidism.
It's divided into several types.
The primary form which can be caused by adenoma or hyperplasia or much less commonly MEN type one or two A or carcinoma secondary hyperthyroidism caused by vitamin D deficiency or chronic kidney disease, and so-called tertiary hyperthyroidism, which is really long-term secondary hyperthyroidism.
The common entity that we're looking for is illustrated in this slide, showing an enlarged parathyroid gland, a parathyroid adenoma.

Symptoms of Hyperparathyroidism

The symptoms of parathyroid hyperparathyroidism are interesting and include depression, renal, calculate bone pain, and you can clearly see that the importance of parathyroid glands in calcium metabolism is at play here.
Fatigue, reflux, and headache.
And this is an odd constellation of symptoms, some of which you wouldn't expect to be included.
But over the years, this has led to a way of describing these as clinically a stones, bones, abdominal groans, and psychic overtones.
This is something I remember from medical school many years ago.

Surgical Treatment of Hyperparathyroidism

The definitive treatment of hyperthyroidism is surgical parathyroidectomy, and the traditional surgical approach is shown here where it was basically a fairly extensive operation that involved a large incision.
And I can't even tell you what all the structures in this picture are, but I know was a lot of surgery and a lot of recovery for the patient.
In recent decades, the trend has been toward a much more minimal surgical approach.
As you see here in the slide from UCLA showing a very small incision to get at the parathyroid adenoma.

Preoperative Localization Methods

Over the years, there's been a lot of interest in localizing the abnormal parathyroid gland or parathyroid glands preoperatively, and this can be done in a number of ways, including 99 m technetium sib scintigraphy, so-called four D computed tomography, gamma probe assisted surgery and ultrasound, which of course will be our main topic for this lecture.

Sestamibi Scintigraphy

Starting off with system scintigraphy, like all imaging modalities, there are pros and cons.
For example, as a pro, this technique is good for single locations, especially atopic glands that are beyond the range of the ultrasound transducer.
A con is that it's relatively expensive as well.
There's some radiation involved and as a corollary to what I said in the as the first pro, it's not really as good for multiple glands.
Here's an example of a positive study provided by one of my colleagues at UAB showing a hot area on the left side, which represents a parathyroid adenoma.

Four-Dimensional Computed Tomography

So-called four D computed tomography hasn't really gained as much traction, but it does offer some advantages.
It's very accurate, but on the downside, it involves ionizing radiation.
It may be sufficient used alone, but it also requires IV contrast.
And the next slides are some illustrative cases from the literature.
This is an article from Hunter Etal and Radiology in 2012 showing the enhancing parathyroid glands with red arrows in various planes.
The utility of this was assessed in this article in 2015 in which the author stated that four DCT provided a positive localization in a clinically substantial number of patients, not able to be localized by ultrasound or scintigraphy.
And here's an example showing an enhancing parathyroid adenoma.

Gamma Probe Assisted Surgery

Gamma probe assisted surgery is quite interesting.
It involves ejecting the same tracer, technetium, SST ibi, but in a smaller amount and then through a small incision in the neck locating the adenoma during surgery with a probe that you see here.
And here is a short video of gamma probe assisted surgery that I found online, and I'll put this in play.
You see the surgeon making a small incision in the neck over the thyroid gland and then enlarging it.
And shortly you'll see them apply the gamma probe that I showed you in the previous slide.
And this is apparently done very quickly.
This surgery takes only 15, 20 minutes on that order, and they're there enlarging.
There is the device that the probe is hooked up to.
And you see the count at the top that shows how many counts are being received by the probe as it's angled in various directions.
And there's the probe in a sterile sheath.
And what they do is insert it and they angle it in different directions, and when the count goes up, they've hit the hotspot and they know where to go, and you'll see the count go up shortly.
There they are, they found it, so they know they're in the right spot over the parathyroid adenoma, and then they are dissecting the parathyroid adenoma out.
You'll see it pop out and there it is.
And again, this can be done very quickly and obviates the need for preoperative imaging there is the parathyroid adenoma, and I'm not going to show them actually removing it, but you can see how they were able to localize this.

Ultrasound for Localization

Ultrasound has been used widely for many years and like everything else, it has pros and cons.
It's relatively inexpensive, but it's unable to visualize the mediastinum.
There's no radiation involved, but the accuracy is variable.
And I've put this in bold as a pro, that is the ability to evaluate the thyroid gland because some head and neck surgeons feel that they want to know if there are any significant lesions in the thyroid gland before they go in and remove one or more parathyroid glands.
In an article published in 2012, these authors found that among commonly used strategies for pre-op localization of parathyroid pathology, ultrasound followed by selective four DCT was the least expensive.
But I will say, and I said this a few minutes ago, that four DCT really has not caught on in many institutions, but like most approaches to various things in imaging, it's idiosyncratic and depends on local practice.
Now, this is a quote that I found on the website of the Norman Parathyroid Center in Tampa, Florida, and they talk about they do many, many parathyroid surgeries every year and they do their own imaging.
And I found the last sentence to be interesting.
They said, if your doctor just orders this test to be done by some technician at the local hospital or radiology center, you're wasting your time and money.
And of course, that can be viewed by radiologist as being a negative.
Unfortunately, if you don't really pay attention to what you're doing in parathyroid ultrasound, then I'm afraid that's going to be true some of the times.

Parathyroid Ultrasound Technique

So what I've liked to do for the rest of the talk is show you how to do parathyroid ultrasound.
And as I have in parentheses here, it's challenging.
Let's start off by talking about why parathyroid glands are hard to find size, location, echogenicity are the three causes.
Starting off with small size, the parathyroid glands have been likened to the size of a grain of rice.
I never quite knew if they were talking about rice before or after it was boiled, but they're small.
Here's the size of a grain.
Here's a grain of rice being compared to the size of a penny.
So not very big, averaging about four to five by two to four by one to two millimeters, not a large structure, but still within the spatial resolution of ultrasound.
So why do we have trouble seeing them?
Well, one other reason is variable location.
And this is an article from 2006 Byman Etal and each of the ovals in part a show various locations of the parathyroid glands that they found in various patients.
And you can see they're all over the place.
And that highlights that you have to look in all these places to try to find the parathyroid glands.
The reason for this variable location is embryologic, as it's shown here.
The superior parathyroids originate with the fourth brachial pouches while the inferior parathyroids originate with the third brachial pouches.
And they essentially switch positions during embryologic development.
So the inferior parathyroids descend with the thymus and can go all the way into the mediastinum, which is why we can't see all of them.
The other reason is they're echogenic because of fat content.
And this is actually from the original article describing the parathyroid glands from the same individual I showed you before, showing a lot of fat content here and here and here.
And as we know, fat is typically echogenic on ultrasound.
There was a study from Japan in 1990 that showed variable fat content.
You can see here on the left content in percent of fat versus number of glands.
And certainly there is a high fat content in a significant number of thyroid glands.
So you take the two factors, they're small, they're very and variable in location as well as being echogenic.
And the way I like to put it is normal parathyroids essentially hide in plain sight.
They're there, we just can't see 'em.
Imagine what it would be like if other organs like the liver or pancreas or gallbladder couldn't be seen normally.
That is if somebody asked you to say, with ultrasound, tell me if the liver is normal and you couldn't find it.
It's similar situation here.
So the way we overcome these limitations is by strict scanning protocol at UAB.
We start off by scanning the thyroid gland for the reason I described before to look at incidental thyroid nodules.
We then look at lymph nodes regionally and finally leave the parathyroid glands for last.
As you know, thyroid nodules are extremely common.
Palpation detects maybe 8% of them from a study by Mortenson etal in the 1950s.
55% are seen at autopsy and ultrasound, working it up to 13 megahertz can detect thyroid nodules in up to 68% of adult patients.
That's a lot of thyroid nodules and many of these are discovered incidentally.
And if you take the term incidental finding, which means something that you detect that's unrelated to the disease or condition that you're looking for, and the Greek suffix OMA for growth from the Greek word soma, and you combine them, you get the term incidental oma.
So most of what we're looking for by definition or what we're looking for in most of these patients in the thyroid gland in patients with hyperthyroid gland hyperthyroidism rather are going to be incidentalomas.
'cause unless they have a parathyroid or a thyroid nodule that's palpable.
Everything you see in the thyroid gland will be incidental.
So there you have your four grains of rice against the background of the large thyroid gland, and therein lies the challenge.

General Technique Points

So let me start off with some general points about technique.
Like for scanning anything in the neck, we have the patient's supine with his or her neck extended.
It's helpful to put up a roll towel underneath to make them comfortable.
We use a high frequency linear array, 10 megahertz or greater with a caveat that I'll talk about shortly.
You may need sometimes to compress or use a lower frequency nine megahertz or sometimes less to see the parathyroid glands.
And I'll show you that in a clip.
It seems odd to say that you ever have to compress the neck to look at anything like you have to with the appendix, but it sometimes is true.
We use gray scale and color doppler and we begin at the submandibular glands and scan coddly centrally and laterally to the thoracic inlet trying to cover all those areas that I showed in a previous slide, which illustrated all the various locations of the parathyroid glands.
And one option that we use at UAB, we can call a back scan, which is we have patients who are in for having their parathyroid gland scan.
We have a second person do a second look scan to verify what the initial person saw or to look for abnormalities that the first person did not see.
So the key tip is to look everywhere.

Appearance of Abnormal Parathyroid Glands

So what do abnormal parathyroid glands whether adenomas or hyperplastic look like?
Well, one clue is from the changing fat content I mentioned before.
This is a normal gland on the left with a lot of fat.
These are all fat globules.
And as the gland becomes more hyperplastic, it becomes increasingly cellular.
So the fat content is relatively less, so it becomes less echogenic.
Let's start off with some images of large adenomas.
Here is one showing a typical hypoechoic pattern and the hypo echogenicity is variable.
They can be quite heterogeneous.
Here's another one in a clip.
And as this moves in and out of the plaintiff's section, you can see how heterogeneous this parathyroid adenoma is.
And again, that's not surprising because the replacement of fat may not be uniform as the gland becomes hyperplastic.
Here's another one, deep to the thyroid gland that I'm outlining with my cursor.
Again, hypoechoic and slightly lobulated in this case.
Here's yet another one.
And here's the thyroid gland in front and the power thyroid adenoma, again, heterogeneous and but generally hypo coac.
Here's one of the largest ones I've ever seen.
This was almost dumbbell shaped more than four and a half centimeters.
Of course this is so obvious that you would see this as soon as you put the transducer down.
So large glands like this, especially if they're not very ectopic, are relatively easy to see.
Color doppler is important.
I'll talk more about it in a little bit.
But typically the enlarged thyroid glands are quite vascular.
I mentioned a little bit about compression, and here's an example, and this is with, you'll see without compression, the gland is visible, but not as well as you see it when you compress with the transducer.
You don't wanna press too hard just enough to bring things more into focus.
So that's a trick I don't always use.
But when it's helpful, it's very valuable.

Smaller Adenomas

What about smaller adenomas?
Well, unlike the four and a half centimeter one I showed you a moment ago, smaller ones can be even more challenging.
And here's an example. I'll show several of these.
There's one over here, lower pole of the thyroid gland and a parathyroid adenoma deep to it.
Here's another even smaller one coming in and out of the plaintiff section right there showing with my cursor.
Another tip that I'll give you is that I always provide the location of the power thyroid gland relative to some landmark, whether it's the interpolar region of the thyroid gland or the lower or upper pole.
I might say, for example, that this gland is located one and a half centimeters cranial or coddled to the lower pole, and the surgeons find that very helpful.
Here's another one, again, there's actually two structures here, only one of which is an enlarged parathyroid gland.
And I'll show why that's important in a moment.
Not all enlarged parathyroid glands are adenomatous.
They can be hyperplastic as well.
And you suspect this when you see multiple glands.
But otherwise, they tend to look just like other para enlarged parathyroid glands.
They're elongated in hypoechoic like the one seen here.

Ectopic Parathyroid Glands

Ectopic parathyroid are difficult.
Of course, if they're in the mediastinum, we're not going to see them, but sometimes they could be located coddle to the thyroid gland and still within the reach of the transducer.
And sometimes, as is illustrated here, we're using a curved array in this case to angle down into the superior mediastinum.
And here between the cursors is a small parathyroid gland.
This is in ectopic.
It wasn't located in the typical location near the thyroid gland, but with some effort it was located.
And here's a clip showing the same thing.
Again, you have to work really hard If you don't see the parathyroid glands in the typical locations near the thyroid gland.
You'll have to look in all these other areas as best you can.
And here's another example of an enlarged parathyroid gland.
It's actually hard to see on this clip coming in and out.
It's this area over here.
As I said, sometimes these can be quite challenging.

Challenges with Abnormal Thyroid Glands

Another source of challenging parathyroid imaging is when the thyroid gland is abnormal.
'cause that occupies a lot of your focus.
Here you see the thyroid gland with multiple hyper coic nodules and the parathyroid adenoma deep to the thyroid gland over here.
And here's another example of a abnormal thyroid gland.
And the parathyroid adenoma is almost looks like it's projecting from the posterior aspect of the right lobe outlined over here.
And here's another example.
This is a patient who's actually had a thyroidectomy.
And those are particularly challenging because you don't have the acoustic window here coming in and outta the plane of section.
Next to the carotid artery is a small parathyroid adenoma.
And here's another example of a massively enlarged parathyroid gland.
Not really a topic, but certainly unusual.
And here's a few other unusual ones.
This one markedly lobulated.
In fact, this looks like it might be a rising from the thyroid gland, but it really is a parathyroid adenoma and quite vascular.

Mimics of Parathyroid Adenomas

What are some mimics of parathyroid adenomas?
Well, lymph nodes, one of the cases I showed you just a little while ago, one of the two structures was a lymph node.
The other is the tubercle of iCal candle, which I'll show you in a moment.
And the third is what I call other non-specific ditzels.
I don't know if ditzels is an official word, but I use it to apply to some other structure that I can't really identify.
And here's an example of a typical lymph node between calipers showing the tip, the usual echogenic, hilum and hypoechoic rim.
And here's the tubercle of ker candle.
This is a normal thyroid structure that you see over here.
These images were provided to me courtesy of bill Middleton and Mallinckrodt.
And here is a drawing showing why this is important.
The recurrent laryngeal nerve runs right by here, so this is an important surgical landmark.
But the important thing is not to mistake it for parathyroid anoma.

Role of Color Doppler

As I mentioned earlier, color flow is very important.
The parathyroid glands or supplied by branches of the primarily the superior inferior thyroid artery as you see here.
And they're quite vascular.
They typically have a vascular arcade around the periphery with penetrating vessels that you see here.
And we look for that in every case.
Here's an example in real time, showing the artery around the edge with a penetrating vessel.
And here is another one.
This is a really small lesion, and when they're really small, they can be overwhelmed on color flow, but you can see this small parathyroid adenoma with a lot of flow in and around it.
Here's yet another one with the arcade along the edge with a penetrating vessel on the right side, and yet another one with a vessel along the edge with some flow within the parathyroid adenoma as well.

Other Causes of Parathyroid Enlargement

There are other causes of parathyroid enlargement I'd like to cover briefly.
This is from the literature.
I have no examples from my own collection of a parathyroid cyst.
These are really quite rare, but otherwise they look like cysts elsewhere.
And this is a parathyroid cancer also from the literature.
Fortunately, very rare.
Some of these are, by the way, are associated with very, very high parathyroid hormone levels.
And this is one example I did have from my own collection of a very vascular parathyroid cancer.
Fortunately rare. These are bad actors.
Um, and otherwise, aside from their size and vascularity look like enlarged parathyroid glands elsewhere.

Intrathyroid Parathyroid Adenomas

One question is whether parathyroid adenomas occur in the thyroid gland.
The fact that I'm asking the question suggests that the answer is yes, which is true.
This is from an article in surgery in 2012 that looked at over almost 5,000 Parathyroidectomy found intra parathyroid adenomas in 53 single in 44 and double or hyperplastic in a minority.
So it does happen. And this is what they look like.
This is from the literature.
This would be very hard to tell from a thyroid th nodule in the thyroid gland because it's almost completely surrounded by thyroid tissue except posteriorly.
And by imaging, you pretty much can't tell these apart, reliably.
Here's another example of one.
It looks like it's in the mostly in the thyroid gland, but is a parathyroid adenoma.

Incidental Parathyroid Adenomas and Ultrasound-Guided FNA

What about incidental parathyroid adenomas?
I gave this talk at a conference several years ago and somebody asked me, what if you see one incidentally?
Well, really most of them are actually thyroid nodules or lymph nodes.
'cause it's unusual to have a parathyroid adenoma without having about chemical abnormality or signs or symptoms.
But if it's truly a parathyroid, no, it's probably not significant.
If the PTH and serum calcium are normal and clinical and lab follow up are usually sufficient, is there a role for ultrasound guided FNA if you see a nodule in the thyroid gland or elsewhere and you're not sure?
Yes. We're starting to do these with greater frequency now, not ultrasound frequency.
We're doing them more often.
One of our endocrine surgeons has been requesting these.
The technique is really similar to thyroid FNA, using a thin 25 gauge or smaller needle.
But the only difference is you do a PTH assay on the aspirate as well as doing cytology in case it's not a parathyroid gland that you're aspirating.
There are some risks for doing this.
Some articles are referred to causing an inflammatory response.
Of course, there's always a risk of infection.
I think these risks are really relatively low with proper technique.
Similarly with the risk of hemorrhage, the risks should be fairly similar to doing thyroid FNAs.
If these things happen, this can prolong the subsequent surgery.
But again, these things are uncommon.

Conclusion

So in some, I hope that I've convinced you that ultrasound does have an important role in the workup of hyperthyroidism.
Even if you're not going to use it to localize the parathyroid glands, it is useful to evaluate the thyroid gland.
The normal parathyroid glands are usually not visualized.
Abnormal glands vary in size and location, and meticulous technique is mandatory as in all areas of ultrasound.
Other causes, including cys and cancer, are rare and parathyroid adenomas may arise in the thyroid gland.
Thank you for your attention.