E65 Masterclass with Jesse Pasternak on Parathyroid Disease

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Chad Ball  00:12

Welcome to the Cold Steel surgical podcast with your hosts Amir Farooq and Chad Ball. We’ve had the absolute privilege of chatting with some amazing Canadian as well as international guests over the past year. While the topics have been brought in range, whether clinical, social or political. Our aims for the podcast continue to remain the same. We hope to inspire discussion, creativity, scholarly research, and career development in all Canadian surgeons. We hope you enjoy our second season as we continue to highlight some incredible guests, deliver detailed masterclass sessions on a myriad of clinical topics and introduce some fresh new features such as debate and companion formats. We hope you relish the podcast as much as we do.

Ameer Farooq  01:12

It is astonishing how a pea sized gland in one’s neck could be so troublesome. Dr. Jesse Pasternak is an endocrine surgeon at Toronto General Hospital. In this episode, we delve into the workup of hyperthyroidism Dr. Pasternak’s approach to parathyroid surgery, as well as his thoughts on the introduction of new surgical techniques.

Chad Ball  01:32

Welcome Dr. Pasternak to Cold Steel. Thank you so much for carving out time in your super busy schedule, all the amazing things that you do we really truly and deeply appreciate having you on. I was wondering if you could just briefly describe for a few listeners who maybe don’t know you as well as we do yet, where you grew up, what that was like, and then what’s your surgical and medical training pathway look like?

Jesse Pasternak  01:57

So first of all, I want to thank you both for having me on. I didn’t know much about the podcast until relatively recently. And then when I first found out about it, I started listening to it, and I thought this was like, you know, what is needed in Canadian even, you know, international surgery. A lot of my mentors have been on it, and it’s just an honor to kind of join them in this podcast. So I really appreciate you having me on first of all. Second, in terms of my journey through medicine, I grew up, you know, in the suburbs of Toronto. My parents, neither of them were physicians, neither of them actually went to university. And my older brother was my first experience with somebody who went to university. And he ended up being a personal trainer and lives in LA now. And myself, I decided to kind of pursue the medical route because I really wanted to, you know, work with people and help people. When my family had some experience with the diabetes, so I wanted to be an endocrinologist actually, when I first went into medical school. And I went in through my undergraduate degree, I went to McGill, for anatomy and cell biology. And I also took a substantial course load in humanities, including, you know, religion, and, economics and international relations and all sorts of hodgepodge of stuff. And then I ended up going to McMaster for medical school. And when I was there, I kind of really was keen on being an endocrinologist. So I spent a lot of time with endocrinologists, I spent, you know, I try to do research and endocrinology, I spent time doing genetics of diabetes work, and then that kind of led me to deciding whether I want to be an endocrinologist, which would be internal medicine. And then I kind of had a couple experiences in surgery. And that led me to an elective I took at UBC, with these general surgery people out there. And I met a chief resident at the time, and then Adrienne Melck, who many of you may know, who is now an Endrocine surgeon in Vancouver, and she actually told me that, you know, you sound like you’re really interested in Endocrinology. I said, yeah, and I really want to be an endocrinologist, but I kind of really, you know, got scooped up by the surgical side. And she said, there’s something called endocrine surgery and I’m doing a fellowship in that coming up. And I said, oh my gosh, that’s insane. So I started looking into it a little bit more and I found out that there’s actually something called endocrine surgery across Canada and there are giants of endocrine surgery across Canada including even at the University of Calgary. Janice Pasieka is one of my mentors and is a giant, you’ve had her on your show. And, you know, she’s really something – a real force in surgery, but also specifically in international endocrine surgery. And if you mentioned her name in any circles around the entire world, not only have they heard of her, but they know her very well. So, you know, I didn’t know that this existed across Canada until I did that elective and once I did that, I started doing my research and when I started my general surgery residency, I started getting into the, the research and the kind of the real clinical side of endocrine surgery. And then did a fellowship in San Francisco with Orlo Clark who essentially started with Norm Thompson, (who Dr. Pasieka did her fellowship with in Michigan). Those two started the endocrine surgery kind of specialty in the mid 20th century. And so, him and Dr. Clark, and Quan-Yang Duh, who is also a big name in surgery, was one of the first people to popularize the laparoscopic adrenalectomy. And being exposed to some of these giants in endocrine surgery made me think, you know, this is something that we can actually expand even further across Canada. Coming back and being recruited back to Toronto is really an awesome opportunity to start an academic career in endocrine surgery. And that’s kind of where I am now.

Ameer Farooq  06:36

I wanted to ask you about your work around decision making for low risk thyroid nodules. I love the stuff that you’ve worked on, in terms of trying to figure out what the best treatment options might be for patients faced with this situation. You know, we of course, interviewed Dr. Urbach about a study that he did, that I think you were also involved in, with looking at the language that you use around thyroid nodules, and then how that impacts patient decision making. What about this topic interests you so much?

Jesse Pasternak  07:09

That’s, uh, you know, this topic is something that we could talk about for hours. And I think the reason is because, you know, the jury’s still out on the way that thyroid cancer, because, you know, people evaluate thyroid nodules, not just for the risk of thyroid cancer, that people in the general public, you know, when they think of cancer, they think of something you need to treat aggressively, you need to make sure that, you know, you don’t leave any cells behind. You have to make sure that if you have a second or multimodal therapeutic option, you use those things. And I think that idea of the treatment of cancer really is not applicable to the majority of thyroid cancers. And so I think I realized that, you know, going through general surgery residency, we were exposed to so many different types of cancers, and so many different types of aggressive cancers in general surgery. In thyroid cancer, it’s a much different story. And, and I think the issue stems from, you know, even up until about 10 or 15 years ago, there were many different physicians. One notable guy is named Dr. Mazzaferri who published multiple papers, saying, basically, we need to stamp out thyroid cancer when we find it. We need to treat it with, you know, total thyroidectomy, we need to treat it with radioactive iodine, we need to treat it with thyroid suppression, I call it the triple three. And in fact, the evidence does not show that when you look at it, when you look at the large studies that we’ve had,what we have now. And one specific example of this, and I always say this in my talks, is that, we have a study that looked at, you know, 50,000 patients in a large American database, and it showed that if you did a total thyroidectomy on them versus a lobectomy on them, where you’re taking out half the thyroid, you actually had a worse outcome if you did a lobectomy. And then another another group, led by Julie Ann Sosa, who is now the chair of surgery at UCSF and a very big force in endocrine surgery. She’s an endocrine surgeon and a surgical oncologist. She’s also an epidemiologist. She reviewed those data a few years later, most of the same similar data with an epidemiologic, endocrine surgical bent to it. And and she found the exact opposite result and in fact, you know lobectomy, we have the exact same outcome. And so I think the idea behind you know, treating thyroid cancer, and that applies to thyroid nodules, is really based on the fact that we need to kind of move away from the previous thoughts of how to treat thyroid cancer in the context of treating other cancers. And specifically regarding thyroid nodules. We worry about thyroid nodules so much because of the risk of thyroid cancer, because we think we need to treat their cancer aggressively. And if you think about thyroid nodules and the detection of thyroid nodules, if I did a thyroid ultrasound on every single person walking down the streets of downtown Toronto or anywhere in the world, I’d have about a 50% likelihood of finding a thyroid nodule in you. And so if we treated every thyroid nodule aggressively, and we worried people about their nodule, we would have no ability to treat anybody else in our health system. And we’d also create a quality of life of everybody that had a thyroid nodule, which is quite concerning. People would be worried about this all the time. So I think the ideas behind what thyroid nodules are, and what thyroid cancers are, really needs to shift and and it’s not necessarily about the evidence, because we have a lot of evidence, it’s about the changing the attitudes towards what is a thyroid nodule and what is a thyroid cancer. And I think those are slowly changing. One example of this: and I’ll just briefly just say this example, is that we’re starting active surveillance trials in Toronto, up to two centimeter thyroid cancers that are diagnosed with thyroid cancers. We don’t actually operate on them and the treatment is to monitor them. And this is based on large data sets from Japan showing that decades of monitoring small thyroid cancers produces patients that don’t need surgery. In fact, less than 5% of those patients actually have any sign of metastatic disease. And if they do have metastatic disease, you can just treat those with the usual surgical management. And they do fine. So up to two centimeters, we monitor and you know, initially when we started this trial, people were like, gasped, like how could you do something like this? And then over the course of the last couple years, we have slowly started to change the hearts and minds of the referring Doc’s and the other stakeholders in the thyroidology world. And in the region, at least where I work, you know, it’s mostly accepted. You should see the kind of hate mail that I would get from publishing some of this stuff. In CMAJ, I published a paper about the escalation of thyroid cancer care, which I got hate mail, you know, I give talks to the endocrinology societies and I get hate mail about that. People would like stand up in the podium and say, you know, how could you advocate for this? And I think, as long as we use the evidence, and as long as we can, you know, at least get the people who are treating these patients on board with the evidence, we’ll be able to treat the cancer adequately. One of the thyroid surgeons at Memorial Sloan Kettering, Ashok Shaha used to say “the punishment must fit the crime”. And so we shouldn’t be doing such big treatment modalities for thyroid cancer, when it’s not actually going to hurt you or kill you throughout your life.

Ameer Farooq  12:44

It’s such a remarkable time to be a surgeon. Like there’s so much evolution in so many different fields, you know, from thyroid cancer, to breast cancer, to rectal cancer, like it really is just a remarkable time. To be a surgeon, it’s fascinating. I think it is only fitting that we use your expertise to talk a little bit about parathyroids. And I’ll just plug you again, that you gave a great talk for us. So every year, the graduating chief residents in Canada, I go to Toronto, for a review course prior to our Royal College exam, which is equivalent to the board exams in the US. You gave a great talk for us on thyroid cancer. So I’m hoping to leverage your expertise again today on the podcast to kind of give us a crash course on parathyroid disease. So let’s just talk a little bit about some basic calcium phosphate PTH metabolism. For the junior resident, can you break down a little bit about how does calcium phosphate get handled in the body? And where does PTH fit into that?

Jesse Pasternak  13:53

So I think that, you know, if you’re going to be reading any of your exams in general surgery, if you have any parathyroid issues, you know, things you got to learn about, I think the best thing to kind of start from is from the beginning. And the fact is that, you know, the history of parathyroid disease, thyroid disease has been long standing and obviously, as many of you know, the first parathyroidectomy was done in the 19th century, and it was done on a guy named Charles Martel who was a captain in the Navy in the US. And he he had parathyroid disease and there’s nice pictures in the literature of him before he was stricken with the parathyroid disease and then after and in fact, he underwent multiple parathyroid surgeries by multiple surgeons at large reputable centers in the US. And they knew that his calcium was high because he had the end- stage calcium issues. And we always talk about, you know, bones groans, moans, psychiatric overtones. But I think that the key parts to parathyroid disease when we’re treating it today, because we don’t really view those manifestations anymore. The main things we talk about is high calcium causing kidney stones and causing osteoporosis. Those are the two main symptoms of parathyroid disease. From a biochemical standpoint, calcium has, since the 1970s, we’ve had a very high throughput, easy to measure calcium test. It was developed in the 70s. And since then, there’s been widespread use of calcium. So calcium is actually the first thing to be seen to be elevated. It’s often seen in an asymptomatic patient, especially in North America. So when your calcium is elevated, I think that’s when you have to try to think about what’s happening with this patient. And as many of you know, the most common reason for an outpatient to have elevated calcium is primary hyperparathyroidism. Now, the phosphate is something I could talk about for a long time. But I think that the take home points about phosphate is that in secondary disease, it’s much more important, and those are patients with kidney disease. In primary disease, you know, it is often low, and that’s related to the kidneys as well. And Dr. Pasieka, he says it’s a poor person’s PTH, you see a low phosphate and high calcium, then you know the patient has primary hyperparathyroidism. That’s sometimes the case, sometimes you don’t actually have a very low phosphate. But I think nowadays, as long as your calcium is elevated, and the PTH is also elevated, that is a clear diagnosis of primary hyperparathyroidism. Unless we talk about vitamin D, and I think vitamin D is actually more important to talk about in the diagnosis of primary hyperparathyroidism then phosphate. So I think the key diagnosis of primary parathyroidism is: calcium being high, or high-normal, the PTH being higher, high-normal, and the vitamin D being normal, because as you know, vitamin D is highly deficient in our population, specifically in Canada. And so vitamin D, that’s very low, can actually cause the PTH to be high. And so if you have a relatively normal or high calcium but your PTH is very very high, then it could be related to vitamin D. And if you get vitamin D supplementation, the PTH and calcium stay normal. So I think vitamin D, calcium and PTH are the most important biochemical factors to diagnose primary hyperthyroidism.

Ameer Farooq  17:45

So let’s say you’re seeing a patient who’s been referred to you because they have a high calcium and high PTH. How do you approach that patient from a history and physical perspective?

Jesse Pasternak  17:58

So the main thing about parathyroid diseases that you have to understand, is you have to have a good approach to these patients in a very stepwise fashion. And I think that’s where the problem lies in the surgical and medical community – is that we jump steps. And so I think if you review a parathyroid patient from a stepwise fashion, you’ll really get it every single time. There’s three questions that I that I usually ask. And this came from Dr. Quandoo, who’s one of my mentors in San Francisco. And he said, the first question he’d ask is: do they have the disease? And so you review the calcium, you review the PTH, you review the vitamin D, and if those things line up, then you have primary hyperparathyroidism. Then if they don’t have that question, you can’t move to the second question. And that’s a key point. A lot of people move to the second and third questions, which I’ll tell you about in a second without actually making the diagnosis of primary hyperparathyroidism. And unless you make that diagnosis, you can’t move on. So let’s say we’ve made that diagnosis. The second question is, should they have an operation? And having an operation depends on two factors. The first is: if they have symptoms? And the symptoms that we know about these days are, as I mentioned, kidney stones and osteoporosis. So if the patient has kidney stones, or any ultrasound findings of kidney stones, even asymptomatic kidney stones, or if they have osteoporosis done by a DEXA scan, which is a bone mineral density scan, then they deserve an operation. The people that don’t meet those two criteria still can get an operation if they meet the asymptomatic guideline criteria. And there’s a host of criteria and those revolve – I won’t go through them – but they revolve around whether the patient’s young, whether the patient has very, very high levels of calcium, or whether the patient has any renal disease. And so if you think about the long term complications of parathyroid disease, it makes sense right? You don’t want somebody that already has renal disease to have even worse renal disease. Renal disease happens because of high calcium over long periods of time. You don’t want them to have very, very high levels of calcium because then they can have inpatient stays related to the elevated calcium. And we can talk about, you know, you probably have reviewed, anyone who’s studied for any exam, how to manage elevated calcium, and many of them require inpatient stays. So you don’t want to have very high levels of calcium, which is also dangerous to the end organs as well. And you don’t want somebody that’s very young, because the younger they are, the longer they’ll live with the parathyroid disease. So I think the asymptomatic patients as well as symptomatic patients deserve an operation. Now the issue I said before, you can’t move onto the next step without having checkboxed that question, applies a lot here as well. People move on without actually making a clear understanding of whether the patient needs an operation. So if you do check this box and say the patient needs the operation, then you can move on to the third question. The third question is: how to do the operation. This is where all the scans come in. So you can see that the first and second question have no connection to scans, yet a lot of patients are referred without fully being worked up and already have scans in place. And sometimes they’re not referred because the scans are negative. Again, not  following the three steps in sequential order. Okay, so the first step is, do they have the disease? Then the second step is: should they have the operation? And the third step is: how to do the operation. And that is depending on what kind of resources, across the world, are available that you have. In my practice, I do two imaging studies to localize disease. And those imaging studies that I do personally are my own ultrasound, so I do a surgeon perform option. And I do an ultrasound on every thyroid and parathyroid patient that I see in my clinic. And I localize the disease, especially parathyroid disease, relatively easily. And then I do a functional scan, like a sestamibi scan. I’ve also done a bunch of studies on other types of functional imaging, like PET MRs, using fluorocholines. And those types of things. But I think from my perspective, the easiest scan to get is a sestamibi scan, which is actually quite a poor scan, but it’s the best functional scan we have available in my region. So that’s what we use. Some people use CT scans, which is not technically a functional scan. But they call it a 4D CT scan, and that’s often used, but I don’t personally use that in my practice on a regular basis. And so if I can localize a lesion, then I’ll do a minimally invasive focused parathyroidectomy. And minimally invasive parathyroidectomy is a very fluid word. A lot of different people use it for many different reasons. And I won’t go into that specifically. But what I will say is that it’s not okay to localize the lesion, take someone to the operating room, take that lesion out and close them up and send them home. Because In my opinion, and in the data, if you do that you have between a five and 10, up to 15% chance of persistence/recurrence rate, and that’s too high for me. So what I do is I do an interoperative PTH value where I check the levels of PTH while the patient’s sleeping, and if the PTH levels go down adequately, and we have algorithms to decide if it’s adequate, then the patient’s cured and the recurrence/persistence rate is probably around 1% or less. If the levels don’t go down, that’s when you convert to the foregland exploration. I can do a foregland exploration fairly quickly. And I would just look at all the foreglands, look at which ones are big, which ones are small. And usually if the PTH hasn’t gone down, they have  either multiple adenomas or hyperplasia. And that’s a long conversation as well: what is hyperplasia? What is multiple adenomas? But I think a foregland exploration is necessary, if you’re PTH doesn’t go down. Now, if you don’t have PTH available in your center, you can still do parathyroid surgery for sure. But I think in that situation, it’s really incumbent to understand what your recurrent/persistent rates are going to be. If you only do a single excision, or a unilateral excision, where you look at two lesions on that side, or a foregland exploration where you look at all four glands, I think that needs to be discussed with the referring doc’s, with the patient and understand your rates yourself – of what your persistence/recurrence rates are.

Ameer Farooq  24:40

You know, I think where people get really confused sometimes is even at that first stage, like you talked about making the diagnosis of whether they have the disease. Can you just explain for our listeners, what’s the difference between primary, secondary and tertiary hyperparathyroidism? And how do you differentiate those things on laboratory examinations?

Jesse Pasternak  25:04

Okay, it’s basically a two-second discussion. Primary disease are patients that have elevated calcium in the setting of elevated PTH or high-normal calcium in the setting of elevated PTH or, you know, an elevated calcium setting of high-normal PTH with  normal vitamin D. Those are all forms of primary hyperparathyroidism. None of those patients have renal disease causing their parathyroid disease. So primary hyperparathyroidism is when the parathyroids themselves independently are causing the problem. So that’s fairly easy. And you can recognize that fairly easily, because the patients are either not on dialysis or has never had a renal transplant. So if the patient  is on dialysis, or has a renal transplant, then those patients are either secondary or tertiary. So that’s a really easy way to kind of diagnose it. I’ll go in further and say a patient that’s on dialysis, that’s not had a renal transplant, has secondary hyperparathyroidism. And almost every patient that’s on dialysis will have secondary hyperparathyroidism. The rates are you know, 75 to 80%, that have substantial secondary hyperparathyroidism on long standing dialysis. So I think secondary disease, dialysis, and then once patients get a transplant, a lot of some people have different ways of classifying them. But from my perspective, once a patient has a transplant, that’s when they can have tertiary disease and tertiary disease usually comes with elevated calcium. On the other hand, we think about patients with secondary disease that are on dialysis, they always have low calcium, because the vitamin D levels are low, they’re not able to simplistically, they’re not able to absorb calcium. And so the calcium levels are low, and therefore, the PTH levels go high to try to normalize that calcium. So it’s a pretty simplistic thing. Primary disease, when the parathyroids causes it themselves. Secondary disease when you have long standing dialysis, and you have stimulation of parathyroid disease, because you have low calcium, and tertiary disease, when you have a kidney transplant, and long standing secondary disease from being on dialysis. Now you have a kidney transplant, and those parathyroid glands have been working so hard for so long, they can’t go back to normal, and they become autonomous and start making elevated calcium.

Ameer Farooq  27:44

Yeah, I think that’s very easy and not hard way to think about those three things, and I wish someone had told me that, you know, five years ago. But I just want to go back once again, just to the diagnosis perspective, like if you ever want to, you know, kill an afternoon and you can start looking at the differential diagnosis for hypercalcemia, on up to date. How do you differentiate, you know, they always talk about these familial syndromes like hypercalcemia, hypercalcemic, all those kinds of things. Are there any other investigations? Like let’s say you have someone who looks like they have primary hyperparathyroidism. How do you distinguish between or rule out those things that might mislead you?

Jesse Pasternak  28:37

So the one test we usually order in primary disease, and you talk about familial hypocalciuric hypercalcemia, when the calcium is very low. Hypercalcemia, and the blood calcium is high. That’s a familial disease affecting the CaSR receptor, which is in the kidney, and that’s the calcium sensing receptor. And in that disease, the body actually pulls the calcium in from the kidney. And so the urine calcium is low. Now that disease is not treatable with surgery. And so the way to rule that out is to make sure that the urine calcium is not very low. And so that’s one kind of test, an adjunct test that we do. It’s very, very rare to have that problem. And so some, some parathyroid surgeons usual practice is to do it for every patient, some parathyroid surgeons it’s not, and they basically just take that risk. But that’s one way to kind of rule out familial hypocalcemic hypercalcemia. The other genetic syndromes are still primary hyperparathyroidism like MEN2, MEN1. These are still primary disease because the gland is itself the primary aspect of the disease itself. The gland is causing the problem. So the other diseases are all still a form of primary hyperparathyroidism. But when you talk about familial disease, you talk about a higher propensity, in my opinion, to multi-gland disease. And that’s what I see a lot, because I do a lot of parathyroid surgery, I see many of the patients that have a family history. So if you take a family history of a parathyroid disease, when you speak to patients, and they tell you, “oh, my mom had parathyroid disease”, or “my sister had her thyroid disease”, that sets off the alarm bells in your mind to say: oh, this may be a familial disease. And as long as their sister or their mom didn’t have pheochromocytoma, you can probably be sure that it’s not MEN2, it’s probably MEN1. And MEN1 disease is actually quite common in some areas, even in Canada, and in some areas in the US. And MEN1 disease is associated with multi-gland disease. So that’s why when I see somebody that has mild hyperthyroidism in the sense of low, low levels of calcium, (they’re still elevated or high-normal), but low levels of calcium, if they’re young, if they have family history, then that sets off alarm bells for multi-gland disease and MEN1. And those are patients that I would do further testing, either genetic testing for MEN1, or other associated syndrome testing, like pituitary workup and stuff like that. As you remember, MEN1, pituitary disease, parathyroid disease and pancreas disease. The three P’s.

Ameer Farooq  31:32

When do you start worrying about things like parathyroid carcinoma preoperatively? Iss there any anything that will kind of tip you off preoperatively that would start you down that pathway?

Jesse Pasternak  31:45

So a lot of people will say if their calcium is really high, or their PTH is really high then they have a suspicion of parathyroid carcinoma. In fact, if your calcium is very, very high, and your parathyroid hormone is very, very high, you still likely don’t have parathyroid carcinoma. I have met some of my senior colleagues. You know, Lorne Rotstein my senior partner. He’s been doing this for decades, he’s probably had a less than a handful of parathyroid carcinomas in his entire career. And he’s a subspecialty, parathyroid surgeon, so parathyroid carcinoma is very, very uncommon. And it’s something that we sometimes recognize intraoperatively. We see that the parathyroid lesion is almost invading, or there seems to be, you know, very fibrotic reaction around the parathyroid lesion. And I think that those are the more more telltale signs.  Ultimately, you know, the parathyroid carcinoma is very, very uncommon. And I’m doing some studies now to look at some of the genetics of it. So if we can actually predict it, because even now, you know, we have parafibromin staining, which sometimes helps us decide if it’s parathyroid carcinoma. But even now, it’s still somewhat ambiguous whether the parathyroid carcinoma is in fact, the parathyroid carcinoma or if it’s an atypical parathyroid neoplasm. And so these are kind of a continuum of atypical parathyroid disease. You know, from the get go. But I think if you have a very elevated PTH, and a very elevated calcium, those kind of set you off to be concerned. But I think it’s still very likely that those patients still have benign disease.

Ameer Farooq  33:25

All right. So I think it’s time to kind of get us close to the operating room here. But before we dive into how you kind of approach the parathyroid operation, can you talk a little bit about the anatomy of the parathyroid glands? Because obviously, I think that’s  the key and in terms of doing a good parathyroid surgery, tell us a little bit about the anatomy of the parathyroid gland and sort of the landmarks that you’re looking for, and thinking about when doing the operation?

Jesse Pasternak  33:58

So that’s something that I get asked a lot, actually. And I think, even when I was even a medical student resident, I was kind of trying to understand the parathyroid glands in the context of the schematic diagrams on the textbooks, and it’s really hard to kind of understand them, because they’re very small, they’re almost impossible to see. I remember being in the operating room many times with my mentors, and they’re like, oh, here’s the parasite. I’m like, yeah yeah, that looks like it. And I had no idea what they were looking at. Zero idea. So that’s a completely normal experience to have. And for any of the residents that are listening, that’s a completely normal experience to have.  You know, it’s like a slightly different tan color than the fat around it. Again, you almost will never see it unless you see a lot of them and that’s what makes a parathyroid surgeon a parathyroid surgeon. Just as an aside, one of my mentors, Ted Young at McMaster, who actually since retired, he said the best localizing study for parathyroid disease is to localize a good parathyroid surgeon. So I think that really tells the tale, the idea that, you know, it’s very hard to recognize parathyroids, unless you have a good understanding of the anatomy, and where you’re going to find them, and you almost don’t even need to see them, you just know where they’re going to be. So in terms of where the anatomy side of parathyroids are, I think the key really is to be able to understand the thyroid and understand where in relationship to the thyroid, you’re going to find the parathyroids. In addition, you have to know where the recurrent laryngeal nerve is running. And that also helps find the parathyroids. And then obviously, the vessels of the neck. So the carotid arteries is what I use as a landmark as well for the first half of the parathyroid. So, two things I’ll say. The first is that parathyroid glands, people call them upper and lower or superior and inferior. But in fact, the anatomical landmark for parathyroid glands comes from the development of parathyroid tissue, which is in the fetal development. And they come from the third and fourth pharyngeal clefts, and the fourth pharyngeal cleft and the third pharyngeal cleft actually flip as they’re descending down into the place where they’re going to be in the lower neck. And the fourth pharyngeal cleft travels with the superior parathyroid gland. And the third pharyngeal cleft travels with the inferior parathyroid gland and the thymus. And so when they come down into the neck, the interior parathyroid gland from the third pharyngeal cleft actually flips and goes in front of the third and basically forms the thyrothymic ligament and the thymus. And so that’s where you’re gonna find the inferior parathyroid gland: just in the inferior aspect of the thyroid, and in the top of the sinus. The superior parathyroid gland flips, as I said, behind the third pharyngeal cleft, so the fourth pharyngeal cleft which is containing the upper gland flips behind the third pharyngeal cleft and forms the superior parathyroid gland in the posterior aspect of the neck. So to make a long story short, the superior parathyroid gland is actually the posterior parathyroid gland. And the inferior parathyroid gland is actually anterior parathyroid gland. And that’s the best in my opinion, that’s the best way to find these parathyroid glands. And so if you’re looking at the thyroid, looking at recurrent laryngeal nerve, and you look behind posterior recurrent nerve, posterior to the thyroid gland, you’re going to find the superior parathyroid gland. And if you look anterior to the nerve in the thyrothymic ligament, you’re usually going to find the inferior parathyroid gland. And that’s how I kind of decide, at least where to start looking.

Ameer Farooq  37:48

Can you walk us through a little bit about how you approach this operation? Let’s say if you were going to do a classic four-gland exploration?

Jesse Pasternak  37:56

So I think maybe you’re talking about like technology and stuff that I use in the operating room? So I think that, you know, we have technology available if your health system can’t afford it. I think you should be using the technology that you have. I’m a laparoscopic surgeon as well as you are, and we use laparoscopy as a second nature, and we don’t think twice about using energy devices for laparoscopy. And I think energy devices is a very effective tool, especially either four-gland or even localized parathyroid disease, because it allows you to make small incisions. It allows you to have a direct view of what you’re doing and you don’t have to worry about ties coming off and these type of things. So I use an advanced energy device for all my cases, if I can. If the hospital I’m working at can’t afford it, then I obviously won’t won’t use it. But if I can. And I also use a nerve monitor as much as I can. The reason I use a nerve monitor is not so that I can kind of truffle find the nerve, which is what a lot of the lot of the surgeons in many different specialties do. The argument they used to not using a nerve monitor because it’s almost like a bravado thing, like oh, I don’t need a nerve monitor to operate. I mean, I think that argument is, you know, maybe 10 years ago. I think I use a nerve monitor because it helps with – because all my cases I do with learners, it helps learners understand the relationship of where they are to the nerve at all times. That’s the first reason. And so whenever I’m getting learners to make a move, I always have them show me where they think the nerve is and then where the dissection plane is going to be, and it actually helps them a lot in trying to understand how to do a safe move around the recurrent laryngeal nerve. Because as you know, that’s the main difference between you know, just plucking something out and something somewhere else in the body and being in the neck. So I do use a nerve monitor. And the second reason why I use a nerve monitor is that it helps understand if we have any stretch in the nerve, and especially when you’re doing a total thyroidectomy, or a four-gland exploration, you know that if you have any nerve signal problem on one side, you don’t really want to go to the other side, unless you’ve waited until nursing come back or that the vocal cord is moving. And that prevents ever theoretically having a bilateral nerve injury, even temporarily, which sometimes requires tracheostomy. So those are the reasons why I use a nerve monitor. And I try to use a nerve monitor as much as I can. And so that’s how I kind of set up with my technology to approach thyroids and parathyroids. In terms of the actual approach to the operation, you know, I usually do a focussed parathyroidectomy even in patients that may have four gland disease. At least I’ll start off with it, and then I’ll move to a four gland exploration if needed. So I think you have to have a good approach for your operation. But, you know, I tried to standardize my operation, that’s really key. All the endocrine surgeons I’ve ever worked with were very, you know, bent on standardization of their operation and that takes out all the variables. Because there’s so many variables that can happen when you’re doing functional surgery, that you try to minimize any of the variables that you can. And that gives you the best outcomes, I think possible.

Ameer Farooq  41:37

Can you just walk us through a four-gland exploration, you know, starting from the beginning, and then walking us all the way through it? And what are the steps and key maneuvers during the operation?

Jesse Pasternak  41:49

Sure, so I guess four gland exploration – what you do is you make your incision in the neck, you’d make yourself  platysmal flaps, you’d split the strap muscles in the midline. And I know I’m digressing. But as a side note, I actually do a focused minimal base of parathyroidectomy using a lateral approach sometimes. You wouldn’t do that for four gland exploration. So, in this situation, you’d split the strap muscles in the midline and you start on one side, you pick a side, you know, whatever you’re more comfortable with. Or at least comfortable with. There was a surgeon that I worked with, and it always started on the right side. Never started on the left, always start on the right. Even in thyroid cancer patients, in doing a total thyroidectomy, in the thyroid cancers on the left, he’d still start on the right because that was more comfortable with the right. So I think you have your own, again, standardization, you have your own way of doing it. So let’s say you start on the right, I’d usually try to find the inferior gland first, because that’s what usually pops out first in the thyrothymic ligament. I’d inspect that and then see what it looked like, then look to the right upper gland. Again, medializing the thyroid gland, away from the carotid artery so you can see posterior to the thyroid gland. Again, you’d have to take, you’d have to make sure the strap muscles were separated from the thyroid gland before you can do that. And then visualize the superior parathyroid gland. And I sometimes put a little clip on it just so it’s easy for me to find when I come back, because I plan to do a four gland, so I’m gonna come back to them. And then I’d go to the other side, take the strap muscles off the thyroid gland. Again, look at the inferior parathyroid gland the same way I looked at the other side. Then review it, is it big? Is it small? Maybe put a clip on it. And then look at the superior parathyroid gland again, medializing the thyroid gland away from the carotid artery away from the trachea. So you can see posterior to the thyroid gland. And review the parathyroid as well. I always find the recurrent laryngeal nerve on nerve as well. At least know where it’s coursing. Again, it’s going to course anterior to the superior parathyroid gland and posterior to the inferior parathyroid gland. And then I will put a clip on it, if I thought one of the big glands was on the other side, I would go back to the other side, take the big gland out. If it was multi gland disease then I would take usually three glands out, maybe three and a half, if the last gland was quite big, but I would make sure that there was good vascularization to the remaining part of the gland. So if I was going to do a three and a half gland excision, I would do the half gland excision first, and then I would start taking the other glands out and every gland I took out, I look back to that first half gland excision to make sure it was still viable, because if it wasn’t viable, then it would just become another full excision gland. I almost never do a total parathyroidectomy and auto transplantation. I think that that’s really not needed in most patients. And the problem with doing that is that they have four to six weeks waiting for that auto transplanted parathyroid gland to come back online. And when I say auto transplanting the parathyroid gland, we basically take that remaining parathyroid gland, we usually take 30 to 40 milligrams of parathyroid tissue, which is the normal size of the parathyroid gland. And we morcellate it, and back into a highly vascularized muscle like the sternocleidomastoid, into a pocket. I usually don’t do that if at all possible, because if you took out all the parathyroid glands and just auto transplanted 40 milligrams of parathyroid tissue, you’d have a four to six week period of zero parathyroid tissue functioning, until that auto transplanted gland started working. And in that period of time, patients are miserable. And it’s dangerous. It’s frankly, it’s dangerous for patients because they either have profoundly low levels of calcium, or they get over supplemented, and their calcium goes too high. So I think those patients are very, very high risk, and I try never to have that. The only patients that will sometimes have that situation are patients that have renal disease, and they’ve had a recurrence of their disease after already a subtotal parathyroidectomy. But in primary disease, I almost never try to have an auto transplanted parathyroid gland, if at all possible.

Ameer Farooq  46:25

I did want to just go back one more time to the tips and tricks for finding these glands. Particularly if, you know. A favorite Royal College question is about these ectopic versus supernumerary glands. So let’s say, if you’re having trouble finding the gland. What are your sort of steps and maneuvers for trying to find a gland that may be in an ectopic position? And how do you differentiate between an ectopic versus a supernumerary gland?

Jesse Pasternak  46:57

So I think, you know, if you can’t find that gland, first of all, for all surgeons that are starting in practice and wanting to do parathyroids, that’s awesome. And you can call me anytime if you have questions. Or even intraoperatively, I’ve had, you know, my previous residents, or even some colleagues call me and say I’m looking here, I can’t find the parathyroid gland. I think it really just helps to have somebody around that knows the struggle, because you know, even as a high volume parathyroid surgeon, I do hundreds of these parathyroid operations a year, I obviously still also have trouble finding parathyroid glands sometimes. And that’s just because, as I said, the nature of development of parathyroid glands, they just don’t always go in the same place every time. And so, as long as you have an algorithm in your mind of what you’re going to do, you can stay calm, and you can kind of kind of get through the operation. And usually, it’ll pop up, the place that you have in your mind to look. So let’s just take the gland. So let’s say you can’t find the inferior parathyroid gland. And you’ve localized it, actually, to that area. And you’ve seen the other gland, let’s say you saw the superior parathyroid gland on that side, and it looks normal. And you’re pretty confident it’s a single gland disease, and it’s the inferior gland. So I think in that situation, you can think back to how this parathyroid gland is formed. And so the parathyroid gland comes, as I said, with the thymus and so I would pull up the thymus. It is usually in the thymus. I’ve had parathyroid glands deep, deep down in the thymus. I’ve pulled it up, and said it’s not here, it’s not here. I’m pulling up. And right at the end, you have this big parathyroid gland pop out. I’ve had that happen a few times. So in the thymus is a really key place to look. Another place is in the thyroid, especially if it’s an inferior parathyroid gland. Sometimes you have thyroidal parathyroids, the superior parathyroid gland could also being the thyroid. So if you can’t find a one parathyroid gland and you found the other ones, especially in four-gland exploration, I would just take out that side of the thyroid and I’ve had many parathyroid glands. Up to 5% of parathyroid glands are in the thyroid, so I just take out the thyroid on that one side. Where else can you find the parathyroid glands? If you can’t find the superior parathyroid gland, make sure you trace the recurrent nerve, and the tracheoesophageal groove. Because it’s often hiding in there. Or retroesophageal, sometimes you can find them right behind the esophagus. And then they can also lie in the carotid sheath, I’ve pulled a couple out of the carotid sheath before. So I think that if you kind of really understand your neck anatomy and and what the critical structure of the neck is, you can clear out the area and try to find the parathyroid, the “ectopic” or supernumerary parathyroid glands in these abnormal locations now fairly well. Sometimes you won’t be able to find it and that is something that we live with. And that is something that we can’t control, especially if you’re a high-volume parathyroid surgeon. And the reason why that happens often is that it’s deep down in the chest, and you can actually pull it up. And I go back to that story of Charles Martel, who had the multiple operations for parathyroid disease. It took, I think, seven, I don’t remember exactly, seven or eight parathyroid surgeries to find his parathyroid gland. And it was actually, they had to split his chest and it was actually beside the pericardium. So parathyroid glands can be places that are not in the neck, and then you won’t find it in a four-gland exploration. And that’s why these are very difficult surgeries sometimes and sometimes very frustrating. So I think we need to, you know, be cognizant that there are non-traditional places for parathyroid glands. We have to have an algorithm, what to do look at all the places, take out the thyroid on that side, if needed, pull up the thymus, look behind the esophagus and around the tracheoesophageal groove. Look at the carotid sheath. But as long as you’re not causing harm, and you’re able to review those areas, and you can’t find it still, then likely it’s not in the neck. And then we’ll have to, you know, close the patient up and figure out our next steps in terms of how to treat this patient.

Ameer Farooq  51:24

The last question I wanted to ask you about parathyroid disease, and this has been a fantastic overview, is sort of defining what recurrent versus persistent disease is, and how you approach both those issues?

Jesse Pasternak  51:39

So persistent disease is very, very clear. The calcium never drops. And that happens at a variable rate, depending on the volume of the parathyroid surgeon, depending on what kind of surgery they did, did they do a focus parathyroidectomy with no interruptor PTH, did they do a foreground exploration? Did the patient have familial disease? These are all kinds of questions, you should tell me these, this is what happened, I can give you a rate of a higher or lower risk of persistent disease. But persistent disease is when the calcium doesn’t drop. Recurrent disease is when the calcium drops, and then it kind of goes back high sometime in the future. And this happens very often in familial patients, specifically in MEN1 patients, and MEN1 patients, let’s talk about that for a second. Because we talked about recurrent disease. This is a classic problem that we as endocrine surgeons face with MEN1 patients. And this illustrates the whole idea behind a recurrent disease. So MEN1, as you as you know, is a disease of all the four parathyroid glands. And so what we try to do at the time of the operation is take out enough parathyroid tissue that their calcium will drop, and their calcium will drop for the longest possible time, before it will recur. Because the parathyroid glands are abnormal, and so even if you leave a little bit, they will become hyperplastic over time, and they will get worse and worse. Or, they’re already hyperplastic, but they’ll get worsening hyperplasia over time, and they’ll continue to increase the calcium level. And so what I try to talk to patients about is that you really want to do a parathyroid surgery on those patients at the last possible moment before they have complications from their parathyroid disease. And you want to do as minimal operation as possible, which will be as robust or will help them as long term as possible. And there’s many different approaches now to MEN1 patients, but I think those patients, it’s really important to factor in two things: number one, how long is it going to be before they need a reoperation? And number two: what is the risk of the reoperation in terms of going into a scarred neck to try to find a small, but overactive parathyroid gland? And that is something that the endocrine surgeon or any surgeon that’s doing this operation should think of before they even do their first operation on this patient. And that’s something that I think is another reason why we like to have algorithms, and we like to have a plan, way, way ahead in advance for the second and third and fourth  complicated operation that these patients are going to have.

Chad Ball  54:17

I wanted to sort of close on on one additional concept and approach, and obviously, it’s the transoral methodology for thyroid surgery. To a lot of us that don’t live in that world. It’s mind blowing, quite honestly. So I’m curious, number one, if you could just describe for our audience that technique very broadly? And then secondarily, maybe what the indications for it are, and where it fits? I’m curious, in particular. I know you’ve spent a lot of time thinking about the introduction of these new and sometimes quite radical introductions, or technologies, I should say into surgery.

Jesse Pasternak  54:56

Yeah, so I really appreciate that question. That’s an area that I’m very passionate about. I mean, so first of all transoral thyroidectomy: people even hear that and they say, what are you even thinking? Why would you even come close to thinking about something like that? Like, that is insane. And to tell you the truth, I actually thought it was insane myself when I first heard about it during residency. And basically what it involves is taking the thyroid out through the mouth. And just to put it into perspective, there’s been multiple different groups of surgeons around the world that have tried to do a minimally invasive approach to thyroid or parathyroid surgery without actually making an incision in the neck. And this comes from the whole idea of laparoscopy. So we, you know, we used to make a big incision in the abdomen, and we took whatever we had to take out. And then, over the course of years, in the last kind of 20 years, we’ve started to say that we can actually do this with cameras. And I think it takes thinkers, you know, outside the box thinkers to try to understand that we can use our understanding of anatomy and tissue planes to try and approach the organs that we’re taking out in a different way. Which, number one,  may obviate the need for a scar. But secondarily, in my opinion, more importantly, the view from a laparoscopic approach, as anyone that does any laparoscopic surgery knows, is way, way better in almost every circumstance, then having an open approach, even if you’re using loops. And so the whole idea behind, you know, this kind of surgical approach to thyroids and parathyroids, you know, started from thinkers like that. In addition, in East Asia, especially in Korea, there’s a big stigma about having a neck incision. And so there was a lot of innovation on trying to do remote access thyroid surgery. There, they use the robot a lot as well. In Korea, they started something called the BABA approach, which was taking out the thyroid through incisions in the areola, or area around the breast and in the axilla. So they actually make incisions in the axilla and around the areola, and they actually tunnel under the platysma and take the thyroid out that way. And that has gained popularity and it’s still going on quite extensively in Korea and East Asia. And then, it was initially Eastern Europeans, but then it was popularized and actually developed to what it is now by a surgeon in Thailand, in Bangkok; named Thanyawat Sasanakietkul. And I went to go learn this operation from him. And he started this operation where you make small incisions, just between the lip, where the lip meets the teeth. Three laparoscopic ports, and you tunnel underneath the platysma and you take the thyroid gland out that way. You actually have an amazing view of the thyroid. In fact, they use a little bit of air, you can use a small suture to suture up the strap muscles, and you review the thyroid gland and you can see the parathyroid glands exceptionally well, you can even use interoperative ICG to view the parathyroid glands even easier. You can review the recurrimental nerve very easily. You can use a nerve monitor as well in a laparoscopic approach. And his operations were done flawlessly. I went to go learn from him. And it’s his approach, his protocol, his outcomes are really amazing. They’re basically the same as most high volume surgeons through the center of the neck. So I think the the approach is feasible, it’s safe, it’s effective. And even for teaching purposes, it’s actually way better. And for any of you that have that have been the second or third assist in a thyroid surgery, you know, you’re not seeing really anything. You have multiple heads in there, and you can’t really see what’s going on. And you know, it’s the same like when I was, you know, a resident and I was the St. Mark’s guy in a rectal case. You know, you’re not seeing anything and when laparoscopic rectal surgery came along, you know, I started being able to visualize everything. So I think it’s a similar kind of idea. And it’s really an amazing view that you have. You know, I think it really comes with people that are passionate about innovation. You’re going to have early adopters, as you know, for any type of new technology or new approach. And then it’s going to take some time for the early adopters to popularize it. And then once it’s popularized, then you have to start teaching people how to do it in the masses, and that’s something that I’m trying to do. You know, we started a new fellowship program in endocrine surgery in Toronto. And I’m doing transoral thyroidectomy. So hopefully the endocrine surgical fellow will take those skills to wherever they practice. And I think that’s kind of the idea of trying to train the next generation and the new technology. And you’re still gonna have people that say, you know, that’s insane. How could you ever think about that, but you have the same people saying that for laparoscopic cholecystectomy, so that doesn’t deter me at all.

Ameer Farooq  1:00:43

You’ve been listening to Cold Steel, the official podcast of the Canadian Journal of Surgery. If you’ve liked what you’ve been listening to, please leave us a review on iTunes. We’d love to hear your comments and feedback. So feel free to email us at podcast.cjs@gmail.com, or connect with us on Twitter @CanJSurg. Thanks again.