Parathyroid Disease Including 4DCT

Introduction

Good morning.

It's my pleasure to talk to you a number of times in the next two days.

We'll start with a topic that's near and dear to my heart.

Parathyroid imaging.

Parathyroid imaging is something that's become more demanded of us in practice.

I think it's largely because the disease, hyperparathyroidism is much more commonly recognized.

It's gone from kind of a an orphan disease to something everybody knows about.

I also have no pertinent financial disclosure.

Outline of the Talk

For an outline of this talk, we'll talk a little bit about embryology and anatomy.

I know it's early in the morning and not too many people like to talk about embryology anytime during the day.

So it's more difficult in the morning, we'll do a little bit of the anatomy, some of the history of imaging, a little bit about minimally invasive parathyroid surgery, which is why we're all concerned with parathyroid imaging these days, and what we're doing in terms of modern imaging.

First off, my job is to keep you awake and hopefully drop a few tidbits along the way.

I will do my best. Let's begin by the anatomy.

Anatomy of the Parathyroid Glands

The anatomy of normal parathyroid glands is that in the typical human animal, there are four, two superior and two inferior.

There are patients who have more than four glands, and there are select patients who actually have less than four glands.

But you can see the percentages are relatively small.

They are very tiny glands, somewhere between four and six by three by one millimeter, and weighing no more than 40 to 50 milligrams, and that's very small.

In fact, the normal gland's very difficult to see on most of our routine imaging techniques.

Embryology

The embryology, and we'll just touch on this, I think that's about all I care to do.

The superiors derive from the fourth brachial pouch and they descend with the thyroid gland.

The inferior derives from third brachial pouch and descends with the thymus.

It is much more likely to have ectopic inferior glands, and they may end up either above or below the final resting place of the superior glands.

Some amorous graphics I'll point out for you along the way, but again, that longer course of descent, much more chance for utopia.

Physiology of the Parathyroid Gland

A little bit about medicine here too as well.

Just to touch on the physiology of the parathyroid gland.

Low levels of serum calcium stimulate the parathyroid gland to produce paraform.

And that does a number of things, including essentially breaking down bone, increasing the absorption of calcium and the increasing the reabsorption of calcium, all designed to increase the levels of blood calcium.

And it's a negative feedback loop.

So as the blood calcium level goes up, the parathyroid glands are turned off.

Hyperparathyroidism

Hyperparathyroidism comes in many flavors, but we'll concern ourselves with only one.

And I will discuss only two briefly.

Primary hyperparathyroidism, which is what we are primarily concerned about as imagers.

These patients have increased serum calcium and typically increased, although occasionally normal paraform levels.

This is a disease of people in their fifth through the seventh decades.

It's a little bit more common in women, and leads to very vague symptomatology.

And unless the calcium or paraform levels are assayed, these are things that are difficult to really kind of glean out in the history.

Moan, stone and groans, perhaps you remember that from medical school.

Depression and calculi and multiple organ systems, just kind of a malaise and muscle discomfort.

Patients with secondary hyperparathyroidism are largely patients with renal disease.

They have normal serum calcium, but elevated paraform.

Etiology of Primary Hyperparathyroidism

So what is the etiology of primary hyperparathyroidism?

By and large. Now, I'll tell you that these are the currently published numbers, but there's a lot of thought that perhaps we are seeing some changes in the overall demographics of the disease.

But at present, what we all think is that around 90% of these patients have a single parathyroid abnormality, a single adenoma, and about 6% have hyperplasia where all four glands are abnormal.

And there are things that are referred to as double parathyroid adenomas.

A lot of us don't believe in this because two parathyroid adenomas, and since you have to have all four glands in your hand to be able to call adenoma versus hyperplasia, we're essentially talking about hyperplasia that involves less glands.

There are very rare parathyroid carcinomas, and we're not gonna talk much about that.

The incidence of hyperplasia is markedly increased in the multiple endocrine neoplasia syndromes.

Role of Imaging in Primary Hyperparathyroidism

So let's talk a little bit about now what our job is as imagers and imaging and primary hyperthyroid is much different than the rest of diagnostic radiology by and large, most of the time in radiology, we are given a patient with some kind of symptom and told to look for something, find a disease, see what could potentially be causing this, or at least being given an organ system to approach and look for something in this disease process.

The patient has a diagnosis and has a lesion, and we know at least based on the numbers, 90% will be a single adenoma that's almost invariable.

And our job essentially is justifying that lesion.

So we know it's there, we have to find it.

And that's a lot different.

Typically in radiology, it's almost like you are searching for the Wiley Russian submarine captain who's got something you almost can't see, and you're hoping that maybe you get a little hint of it.

This is different, right? I mean, this ought to be finding a lesion that's there.

It should be shooting a fish in a barrel.

That's what you would imagine.

But I will just leave you with this thought.

Shooting a fish in a barrel means different things to different people that is shooting a fish in a barrel, and that is way different.

And sometimes when I'm looking for these lesions, this is more what I feel like, and occasionally I'm shooting my foot or the barrel.

History of Parathyroid Imaging

As I'm looking a little bit about the history of parathyroid imaging, it has been in the imaging radar for a long time.

The early methods angiography or venography, venous sampling ultrasound was used very early on to evaluate the neck, and certainly it has been used for parathyroid and the idea of technium thallium subtraction studies, also selective angiography was actually relatively good.

It was an invasive study, but it was successful in finding parathyroid adenomas.

They tend, they're shown to be hypervascular, which is important as we get to more current imaging techniques with a prolonged stain.

So finding either a hypervascular lesion or circumscribing vessels around the lesion was very strongly correlative to the existence of a parathyroid adenoma.

And here's the typical case.

Selective injection shows this little hypervascular nodule, and that's pretty good in a patient with primary hyperparathyroidism, this patient with an inferior pole parathyroid adenoma, again, selective angiography and a lesion, it's hypervascular that is very indicative of this diagnosis.

Retrograde venography also worked, turned out to be a very successful study as well, and there was much less chance for technical failures.

You didn't have to be as good an angiography to get into those veins.

Venous sampling came along at about this time, and again, it was shown to be very successful in localizing the lesion where there is elevated piriform levels, there is a parathyroid adenoma.

Angiers are kind of the same animal.

If your only tool is a hammer, then everything starts to look like a nail.

If it is hypervascular, I can't embolize it.

And indeed they did, and it was quite successful.

The lesions, particularly that could not be found by surgery, mediacy adenomas that were hypervascular were very often embold.

The review of their embolization success rates was not bad.

Angiography was very successful at finding the lesions about 85%, and the success rates for embolization not bad.

But you know, again, you have to consider that most of these patients were primary surgical failures.

Minimally Invasive Parathyroid Surgery

Now, why are we where we are today with parathyroid imaging?

Traditionally, parathyroid surgery was a big bayonet incision and explore the neck, look for the lesions.

And in fact, John Gottman, who wrote a lot of this early literature on parathyroid disease said, and this is not that old, this was from 1991.

And I don't view that as ancient literature in any regard.

Wrote, and I'll just leave you this a little highlighted thing.

There is no evidence that preop, preoperative localizing studies shorten operating time or prevent surgical failures, and that's in 1991.

So what has changed?

What makes us now so keen on finding these lesions and being so accurate?

Well, plainly, it's minimally invasive surgery.

So minimally invasive parathyroid surgery is the way that patients are treated these days with a single lesion.

It's a small skin incision overlying in parathyroid adenoma.

You know, it's very little discomfort for the patient.

They go home the same day, everybody's happy.

Localization, however, is paramount.

And the surgeons are doing a lot of interesting little techniques to try to be more accurate in where their incisions are and how they find the lesions.

Intraoperative ultrasound, intraoperative nuclear medicine, and probes, anything to make sure that your incision is right over the lesion.

Current Imaging Paradigms

So here is how I look at the current imaging paradigms.

And again, this was flavored a little bit by opinion, but I think the literature bears me out.

Technium nine nine SSAB scans are the agent of choice and are almost invariably the first line imaging study in the investigation of patients with parathyroid disease.

Prior studies had been subtraction techniques, but sesames is really wonderful because it has a very high affinity for the parathyroid gland and persists.

So we get early and late images when we look for persistent increased uptake indicating the parathyroid disease.

Planar inspect imaging.

Well, it's really nice if you can do spect and it's even better if you confuse those images.

The sesame B findings, most of these lesions demonstrate increased uptake.

There are lesions that do not, and again, there's a fair amount of investigation going on to see which lesions tend not to, but it's really nice if they do, it allows you to accurately localize, see that lesion early on.

They tend to have persistent activity again, on the delayed scans.

If you do spect, you will increase your sensitivity at finding the lesion and certainly better depict the lesion in terms of its localization.

If you fuse the lesion or fuse that SPECT with ct, you will do even better at finally, at precisely localizing that lesion for surgical management.

Intraoperative localization with probe has also been fairly popular.

So if the sesame's done the same day as the operation, if a very good idea of where the lesion is and the surgeon can use an intraoperative probe to very accurately perform a small incision.

So a typical patient here, planar imaging at 30 minutes and at four hours increased uptake in two separate lesions.

A little inferior pole lesion, very nicely seen.

Small field of view using a pinhole collimator gives you the best images.

Some people like to do just plainar, AP two obliques, maybe a lateral exam to make that diagnosis.

Again, SPECT will increase our sensitivity at finding these lesions.

The literature supports that, and it is a kind of a common sense thing.

So much better depicted when we do SPECT imaging in combination with our nuclear medicine examination.

But again, if we wanna get that anatomic localization, that fusion of SPECT and CT makes everybody very happy.

Now, we can not only see the lesion on cross-sectional imaging accurately depicted in terms of anatomic localization, but show the increased uptake in that lesion, which is a very confirmatory kind of evaluation.

You can do these nice 3D pictures and everybody likes those.

They're kind of cool and you know, they end up being on the cover of most of your brochures.

This is an ectopic mediacy adenoma and again, that fusion of SPECT and pet very nice in a area that no one likes to go treading into.

And it becomes a lot more complicated.

It's much nicer to have that confirmatory bit of evidence with the increased uptake and the anatomic localization from that fusion.

Ultrasound Examination

Ultrasound examination is also very commonly performed and is also very important as we all have heard and know and preach.

The problem with ultrasound, it is a very operator dependent, and everybody prays to get that really wonderful ultrasound technologist and they're in high demand and everybody knows who they are and everybody out tries to outbid everybody to get them.

But it is an operator dependent study and it can be a bit problematic.

However, there are very good results published for parathyroid adenomas in the expected locations.

Your confidence in screening the entire neck can be a bit suspect.

And again, it's wonderful if you see it because you saw it and you know what it is.

If you didn't see it is because you saw it didn't know what it was or maybe you just didn't see it.

And that's always the problematic part.

Mediastinal lesions not seen at all and lesions in the T groove really require somebody to work hard angle the translucent and try to get back there to depict that lesion.

They tend to be hypoechoic.

Dopper is very strongly confirmatory.

You find that polar artery and that makes it much difference in appearance in the lymph node where everything comes in and out of the hilum and you have that central hyper coic hilum structure.

The literature even says that this idea of finding that polar artery is so important that they recommend if you're not sure, you haven't seen anything you're convinced of to just track vascular structures that you see within the ecstasy.

If they terminated anything, that can lead to a fairly long study.

Not everybody does that, but if you're convinced you think there's something there, it's not a bad idea.

So this patient has primary hyperparathyroidism and here is a small lesion on cross-sectional ultrasound exam that is hyper POA coic in relationship to normal thyroid.

And you turn on the Doppler and you get a little polar arterial venous structures.

That is very strong evidence for parathyroid adenoma and again, correlate that with your other examinations.

Another lesion, again hypoechoic and with a polar artery and vein, very strongly indicative of parathyroid adenomas in this patient subset.

Here's the cross-sectional imaging that correlates very nicely with that.

A little lesion stuck behind the thyroid gland.

Here's a lesion down, kinda like a little bit lower in the neck and the sagal images, again, hypo coic, but with this polar arterial structure, no hyper coic hilum, again, strongly evident of parathyroid adenoma.

And here is the corresponding cross-sectional anatomy, the CT examination demonstrating that lesion.

Magnetic Resonance Imaging (MRI)

MR has been used.

MR is not what we typically go to these days, but we do occasionally get the request to evaluate patients for primary hyperparathyroidism with mr.

The classic description in the literature is a hypo intense lesion on T one that's hyperintense on T two.

It enhances uniformly and intensely may be difficult, unfortunately, to distinguish from lymph nodes and particularly visceral compartment nodes.

That can be very problematic to us on mr.

One of the nice things about reviewing all this literature and looking back at Mr.

The MR folks were very early in their detail of the difference in signal characteristics of these lesions.

And that leads to a lot of variations that we still see in some of the larger adenomas.

So they may be fibrous, they may be hemorrhagic, and some alteration in these expected patterns has to be expected.

There's a very typical lesion on the MR examination, slightly hyperintense on T two.

You gotta be looking pretty hard.

I think you have to be pretty full of coffee in the morning to make sure you see that little lesion.

This lesion is much more conspicuous and fat suppressed T two winds or stir.

So here on the stir sequence, very hyperintense lesion.

Now I think you all know that that's pretty idyllic.

We're not gonna see that very often, but if that's the examination, you find that I think it's pretty strongly evident.

This patient has primary hyperparathyroidism and has another really strongly positive lesion.

Increased signal intensity on stir enhances pretty uniformly and intensely.

And just notice the conspicuity of this lesion on stir versus the normal T two.

Really nice to have that fat out of the way.

Computed Tomography (CT) and 4D CT

Let's talk about CT for a bit though, and that's where we're gonna kind of spend a little bit more time.

CT was used early on and it certainly was one of the early described potential uses for CT very early in the CT literature, but it thought out of favor for a number of reasons.

The sensitivity and specificity were both very poor lymph nodes looked just like parathyroid lesions, smaller lesions, you know, when we were scanning in the era of seven and eight millimeter thick slices, it's tough to see a three or four millimeter lesion and they could obviously be confused with lymph nodes, but we are all now scanning with multi detector scanners.

We're all scanning at somewhere between 0.625 and 0.5 millimeter thick sections.

That's what we have to kind of draw on to review.

So our identification of localization has improved for just about any kind of very small lesion.

What is very current and what has kind of got us all a lot more interested in CT these days, however, is four D ct.

And we'll talk just a little bit about that cross-section imaging on a ct, finding that patient.

This is a 60-year-old primary hyperparathyroidism.

This is a very useful style of reviewing the exam, kinda like finding the bumps across the neck and the thyroid gland, the crowd in the jug and the scaling musculature.

So as you go across the other way, you got 'em all, but you know, you got another one and that's your little lesion.

That's the parathyroid adenoma sitting back behind four DCT is very topical, very current, and I would imagine if I talked to most of the radiologists in the room, you have had that request.

You've had someone inquire as to whether you do this kind of imaging.

We started out offering it and now we're pretty routinely doing somewhere between four and six exams a week.

We have a pretty busy endocrine surgical service too.

Four D CT rep applies and refers to multi detector CT that is obtained in various phases of the perfusion of the tissue and concern.

In this case, we're looking at parathyroid tissue.

The typical app acquisition is a non-contrast exam and at least two examinations after that that are post contrast.

And what we're then looking at is the dynamic behavior of that tissue and what we want for parathyroid adenomas.

And again, we're harken back to the early experience.

Dr. Doman and the folks at NIH with angiography, they're hypervascular.

So we tend to see early peak ification and again, the hypervascular nature, they wash out quickly.

So what we'd like to see, and there's a lot of literature about this, the density change you should see in the temporal characteristics.

But what we'd really like to see is something that stains very quickly, at least as much as a thyroid gland, perhaps more and on the delayed examination has washed out and is lower in density than the enhancing thyroid lymph nodes.

That's our typical distinction.

Lymph nodes tend to slowly and progressively a pacify during the course of a typical dynamic examination.

So we like to get these pre examination and early and a delayed set of images and in this case this tiny lesion here, parathyroid tissue behind the thyroid gland.

Reconstructed images can really nicely show sometimes these longer, more fusiform lesions very nicely shown, and again, washing out on the delayed image.

So it is conspicuous against that persistent contrast stain in the thyroid gland and in again, that appropriate clinical setting, strongly indicative of depiction of parathyroid tissue.

Four D CT was initially proposed in the actually in a surgical journal, a journal surgery in December, 2006.

The same group at MD Anderson has published a lot on the technique of 40 CT and it seems to work really well.

In fact, they've even shown it in the very problematic group of previously operated next to be good.

This is the initial paper. I strongly encourage everybody to read this, and in their series four DCT beats sesam and ultra sonography, even as a combined study, both in sensitivity and specificity and very importantly in that important topic of anatomic localization, the pluses of four DCT.

Well, you get that functional information.

So hyper perfusing parathyroid tissue should be distinguishable from other structures in the neck and you can look at all parathyroid tissues.

So finally we have a study that makes us pretty confident when we are evaluating patients with hyperplasia.

The anatomic information that's pretty obvious, there's a really high spatial information, thin session ct.

I can show a surgeon in very confidently where that lesion lies.

The minuses. Well, I gotta give patients hiated contrast media and very importantly in the current era, I have to radiate patients and I have to radiate them not only once, but perhaps two or three, and if you look at the old studies four times for what has what was reported with four DCT and you know, you realize this is for a benign disease.

So you have to really think about it.

You have to use very carefully the techniques on your scanner.

Use any kind of dose limiting factors that you have and use it optimally to try to keep the exam at a relatively low radiation exposure.

There's always that potential for exam mistiming and boy, that really hurts.

I think that really this is an examination that requires physician monitoring to be done correctly to interpret these images.

You know, obviously it's a know your enemy, where are they hiding?

So if I know the typical locations, that's where I'm gonna spend extra time.

Now, obviously I gotta look at the whole neck because ectopic tissue occurs, but you have to look hard and really spend time looking at those typical locations.

So unfortunately there's really no experience, no substitute for experience and a very careful review of the exams.

And this is the kind of study that's gonna take you a little while to read the problematic issues in evaluating any patient with parathyroid disease, ectopic lesions, patients who have existing thyroid disease, which really complicates the images we get.

And finally, hyperplasia, multi ular disease.

Problematic Cases

So here's a problematic case.

This patient had primary hypoparathyroidism and there was difficulty in localizing any gland.

But on the ultrasound examination, there is a hypoechoic lesion within the thyroid.

So you turn on the doppler and you know, no hilar structures, it's hypervascular, it looks like it could have a polar artery, fairly nicely depicted, nicely defined against normal thyroid.

It's already labeled, but that is indeed an intracapsular interra parathyroid adenoma.

Nice to confirm with another study.

And here's the spec, CT STO examination.

And again, I think that sells it very firmly.

Very nice depiction of a lesion in a pretty widely little location within the thyroid gland.

This is another problematic case.

This a 52-year-old with primary hyperparathyroidism.

The prior SST was reported as normal and the ultrasound was previously reported as normal and there is a very small lesion down in the chest, anterior to the arch of the aorta, which enhances like crazy, washed out appropriately.

That's a tough cell to sell to the surgeon, but that lesion was ex excised and that indeed was parathyroid adenoma.

Here's a more typical problematic case.

You're gonna see this patient with multinodular thyroid disease had had previous thyroid biopsies and a couple neck operations prior has primary hyperparathyroidism.

The sesame was thought to represent multiple ular disease, but it wasn't diagnostic.

Big lesion tucked back in the T groove.

That's gonna be hard to see with ultrasound.

And depending again on its uptake with sesame, that might be a problematic lesion.

Just show you what it looks like on the reformatted images.

I think it's quite conspicuous.

Again, I routinely now do coronal sagal reconstructions of both the early and delayed examination in all of our cases.

I think it just is quite helpful. Here's the VR images again, if you surgeons like this or if you like to do it on the workstation, more power to you.

Sometimes they're very nice images and I think they do a really good job of selling that localization.

Parathyroid Hyperplasia

Parathyroid hyperplasia.

Again, enlargement of all the glands.

Again, remember it's pathologically impossible to differentiate an adenoma from a hyperplasia.

You gotta have all of them. Again, more common in the MEN syndromes.

So patients with hyperplasia, again looking for multiple glands.

My dictum is I find the one I'm not done.

I gotta keep looking scour through the whole neck and see if I see additional lesions.

This patient with multiple enlarged glands.

This patient went to surgery and they took out this one and the paraform levels didn't drop.

They took out the next one. The paraform levels didn't drop.

They took out the next one.

The paraform levels didn't drop, so they took out half of the last gland before they got an intraoperative drop of paraform levels to make them happy.

This patient also with multiple gland hyperplasia.

This case loan to me by RO Holliday.

Lots and lots of tissue within the neck, multiple parathyroid glands.

This patient actually with secondary hyperparathyroidism and typical bone changes.

Multimodality Imaging

I like to cheat. I say that freely. I think that's fair.

I like to do the four DCT and the ultrasound.

I like to do at the same time.

Multimodality imaging.

I think that's perfectly appropriate.

This is a wily disease.

I like to have anatomic localization and I like to confirm that indeed it's parathyroid tissue.

We like to do the studies at the same visit.

It's really convenient for the patient.

And I'll give ultrasound another look if they don't see it the first time.

Why I cheat? Well, I like to be confident in my diagnoses and I like to make sure that I'm saying the right thing.

Sometimes the questions that I have, whether it's a node or not, may be negated by what I see in ultrasound.

Sometimes vice versa.

High concordance equals very high confidence in diagnosis.

In my humble opinion, you should always cheat in cases of prior negative neck explorations or in cases that are post-op exams when that patient's already been operated on once, I really want to be confident in a diagnosis.

Representative Cases

A couple representative cases just to close with this, is a 49-year-old female had primary hyper parathyroidism.

The sesame was questionable.

They thought there was something in the median sign, but they weren't sure the neck ultrasound was normal.

Here are some selected images from the four DCT examination and very nice depiction of an additional structure just deep to the sternum representing that para Thom.

We got another crack at this patient on sesame and I think our SST ebe was either more definitive confirmatory or just made everybody feel better increased uptake corresponding to this lesion.

This was excised parathyroid adenoma.

This patient has a long history of hyperparathyroidism and had pri prior bilateral neck exploration.

They removed a couple glands and they were hyperplastic, but paraform levels did not fall.

Here are the early arterial and washout images and again, very dramatically enhancing on the early arterial phase and wash out almost to the level of muscle on the delayed exam.

I think that's really conspicuous.

Here's the SST EBI examination and the reformats.

This patient went to subsequent excision of this gland and half of that gland as well to finally get their paraform levels.

This case actually been published by Jenny Hong down at at Duke, a really nice case of bilateral gland.

And the last case I'll show you, this lady had persistent hyperparathyroidism and already had two and a half glands excised.

So we did the 40 ct.

I just leave that there for a second.

It's tough to see this little guy.

This case loaded me by Larry Ginsburg and it's this is tough.

I think you gotta be pretty full of coffee to see this guy and I'll show you the SPECT in a minute, which makes it a lot easier.

But just notice there's a little notch in the back of the thyroid cartilage.

It enhances like crazy and it washes out.

There's the spect CT fused images and if you see that, I think you get your gold medal.

That's pretty good.

This little tiny lesion stuck back adjacent to the thyroid cartilage was the additional para parathyroid lesion.

Conclusion

So in conclusion, I think parathyroid imaging is a whole different game than what we do with most of diagnostic radiology in that I know it's there.

I just have to find it. I know it's hiding somewhere within the cross-sectional imaging study I have this idea of multi minimally invasive surgery has really driven us to be accurate and to detail very carefully where we see the lesions.

Everything has a role to play.

I think everybody kind of is in the pool on this one.

Nuclear medicine and ultrasounds seem to be good first line studies, but four D CT is very important and perhaps we'll be seeing more.

Mr. Thank you very much for your.