JournalReviewinEndocrineSurgeryPHPandFracture
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[00:00:00] Hello. We are the endocrine surgery team from the University of Wisconsin, and we are doing a journal club where we're gonna talk about primary hyperparathyroidism and how patients benefit from parathyroidectomy. Today we're gonna be presenting two cases and three journal articles.

Hi, my name is Amanda Doubleday. I'm an endocrine surgeon in a private practice affiliated with the University of Wisconsin. I'm a fellowship trained endocrine surgeon, and I will be here today for the discussion of Parathyroidectomy and its benefit on skeletal system and bone loss. And I'm Simon Holbeck.

I'm a fellowship trained endocrine surgeon, board certified general surgeon affiliate with University of Wisconsin Health. And I also have a focus practice in endocrine surgery. And our senior surgical perspective today will come from Dr. [00:01:00] Becky Sippel, who's an endowed professor of surgery and division chief of endocrine surgery at University of Wisconsin, Madison, and the most recent past president of the American Association of Endocrine Surgeons.

Thanks so much for having me be part of this. I'm really excited to be here. Parathyroidectomy is a huge part of my practice and something I'm really passionate about and I'm excited to share some of my insights. So I'm looking forward to the discussion. Our team has no relevant disclosures on this topic today.

Primary hyperparathyroidism is an underdiagnosed condition, which leads to decreased bone mineral density fractures. Kidney disease among other symptoms that can decrease the quality of our patient's lives. Moreover, once diagnosed, only about a quarter of patients end up being offered a parathyroidectomy.

Whether it's for a variety of reasons, including misunderstood indications, misunderstood benefits of surgery, non localized disease, or for other reasons, we thought it was [00:02:00] worthwhile to review the relevant literature demonstrating this disease process and the benefits of surgery. We specifically chose.

Three papers which discuss fracture and osteoporosis. Bone mineral density and osteoporosis is a significant issue in our aging population. Hip fractures carry a nearly 50% one year mortality. Parathyroidectomy has a significant impact on reducing the risk of fractures in patients with primary hyperparathyroidism, especially those with evidence of decreased bone mineral density.

Our first paper today describes the natural history of primary hyperparathyroidism and its impact on a patient's skeletal system while the second paper. Specifically discusses the impact of parathyroidectomy on women with evidence of decreased bone mineral density. My third and final article reviewed today we'll talk about the fracture risk after parathyroidectomy in patients with both normal as [00:03:00] well as abnormal bone mineral density.

Amanda, do you wanna jump into our first case today?

Yes. Great. Thank you Simon. So our first case is a 55-year-old female. Bone mineral density showing osteopenia with following T-score. T-score at the femur was negative 1.6, lumbar spine negative 1.5, and the forearm negative two. She underwent several lab testing, which revealed mildly elevated calcium at 10.4, elevated PTH of 90 and a 24 hour urine calcium at two 20, which is.

High normal, depending on what your, your lab considers normal. She had normal vitamin D, normal kidney function, normal GFR, no history of fracture, kidney stones, or other GI or psychosomatic symptoms. Her past medical history is otherwise unremarkable. She never had surgery and she doesn't take any medications.

So, first question here [00:04:00] for Dr. Sippel. Do you think that this patient has a diagnosis of primary hyperthyroidism? Yes, I think she does. You know, I think anytime I'm evaluating somebody with primary hyper parathyroidism, I think really the first step is, is am I convinced of the diagnosis? And so while this patient has mild labs, she has mild hypercalcemia, and if the parathyroid hormone is working appropriately, it should be suppressed.

And so the fact that her PTH is high, normal or mildly elevated, really does not make sense and is consistent with hyperparathyroidism. I think especially in these cases that have mild disease, it's important that we rule out other potential causes that can mimic that. So it's important to look at their vitamin D levels, make sure that they don't have a vitamin D deficiency.

We also wanna check their kidney function, make sure that they don't have secondary hyperparathyroidism from renal dysfunction. And we also wanna make sure that they don't have FHH. So this is the one [00:05:00] scenario where it's really important to check a 24 urinary calcium to ensure that that's not abnormally low.

But I think in this case, there's clearly evidence of a diagnosis. I think what's also helpful is to look back to, to sort of see the history of it, and I think oftentimes when you look at this, you'll see that this patient probably has had a mildly elevated calcium for potentially five to 10 years. Sometimes these patients with mild disease end up having a much longer duration of disease, which is why it leads to the negative impacts on their bone.

I think regarding her bone density, it's interesting to look, and this is a very common pattern that we see, is that the, the forearm bone density is often the worst site just because it is preferentially impacted by PTH. And so anytime you have a bone density, if they did not include the forearm, it's important to add that because it often may upgrade a patient to a diagnosis of osteoporosis.

Absolutely. That's a really good point. I can think of another case I just had recently where the patient was observed with [00:06:00] clearly biochemical evidence of hyperthyroidism for many years with a normal bone density, and then they repeated it, including the forearm, and she had osteoporosis based on her forearm T score.

And so that was what prompted finally the referral. But unfortunately this patient probably had the diagnosis about 10 years ago. So, all right, so that brings us to our, the second part of our clinical question is, will this patient benefit from a parathyroidectomy so we can try and support our clinical decision making with our first article?

I'm gonna discuss here. This was an article from Columbia University in New York, and it discussed the evidence of the natural history of primary hyper parathyroidism and the impact of prolonged hypercalcemia and excessive PTH exposure on the patient's skeletal system. This was from the Journal of Endocrinology and Metabolism from 2008.

It was titled The Natural History of Primary Hyper Parathyroidism With or Without Parathyroid Surgery After 15 years. [00:07:00] So this group conducted an initial 10 year prospective study and then finalized this paper after an additional five years of prospective follow-up data to, to look at the 15 year postoperative or.

15 year time period between patients who either underwent surgery or who didn't. So their cohort included 116 patients. The majority of them were symptomatic. 51% of these patients ended up having a parathyroidectomy after being diagnosed with primary hyperthyroidism. A hundred percent of these patients normalized biochemically, postoperatively and showed an improved bone mineral density in the 49% of patients that underwent observation.

A majority of them did show disease progression over the 15 years. So in the non-surgical group, they showed no significant changes in biochemical markers and showed a decline in bone mineral density over that 15 year time period of the patients who had kidney [00:08:00] stones. They all showed progression of disease and recurrent kidney stones in the surgical group.

All patients had successful surgery. They showed a significant increase in their bone mineral density, but this was actually sustained for the entire 15 year follow-up period in all skeletal sites that were tested. And so in summary, parathyroidectomy led to normalization of biochemical markers and sustained increases in bone mineral density.

And so this raises the question really, should patients with primary hyperparathyroidism that don't necessarily meet the strict guidelines for surgery, should these patients be observed? And I think that this. This study highlights that there are clearly benefits that patients will see after parathyroidectomy, even if they have mild disease.

Yeah, I think this is a pretty compelling article that just, you know, really demonstrates the benefit of parathyroidectomy and really questions watching patients you know, [00:09:00] observing a patient with you know, clear disease you know. While maybe well intentioned really makes you, you know, sort of question this approach when surgery really does offer a lot for these patients.

I think when I look at this paper, one of the things that sort of stands out is people wanna focus on the improvements in the bone density. And yes, there is a small improvement in bone density, but that's not really where the benefit for patients is. It's really in that 10 and even the 15 year follow up, it became more evident.

Is that it is whatever that bone that people build back, that 10 to 15% improvement, they maintain it for another 10 to 15 years. And so really, if a patient has a reasonable life expectancy, they are going to see those benefits. Over the next 10 to 15 years. So what really happens is it really prevents that expected age-related loss that would continue for most patients.

And so the benefits become wider over time. The longer you follow a [00:10:00] patient, the greater the benefits. There are to intervening with Parathyroidectomy, and I think it's, as I look at that data, that really makes me question why we should wait until they get osteoporosis to intervene. I think it really makes sense as long as we start seeing them develop osteopenia and they're heading in the wrong direction, the sooner we can halt that loss and potentially build back some of what they lost the, the greater the benefit for the patients.

Yeah, that's a great point. And that's a really nice transition into the second paper I wanted to talk about, which looked specifically at women with osteopenia versus osteoporosis and and what were the postoperative outcomes. So this was a recently published article in 2024 titled PARATHYROIDECTOMY Improves Bone Density in Women with Primary Hyperparathyroidism and Postoperative Osteopenia.

And of this patient cohort, 80% were relatively asymptomatic. They had mild disease [00:11:00] and you know, historically a lot of the papers have looked at osteopenia versus osteoporosis, but they've pooled men and women of of all age groups. And so this particular study looked at primarily postmenopausal women with osteopenia versus osteoporosis.

And their aim was to study their post-surgical bone mineral density in these two groups. And they looked at pre and one year post bone mineral density in all sites and biomarkers. And what they found is that. There was an improved bone mineral density in all sites. In all groups, so both osteopenia and osteoporosis showed similar improvements in bone mineral density in the lumbar spine, forearm, and the hip, and they also showed decreased biomarkers that indicated bone loss.

So to circle back on our clinical question, this 55-year-old female with biochemical evidence of mild hyperparathyroidism, osteopenia, would she benefit from surgery? And I think that this data clearly [00:12:00] answers our question that yes, that she would. Yeah. So Dr. Sip. Yeah. How do you clin counsel your patients?

Yeah, I think that realistically, like I don't think, you know, even though the NIH consensus guidelines say of a diagnosis of osteoporosis, I don't think there's any reason why we need to wait till they have frank osteoporosis to intervene. We know that we can never reverse a hundred percent of the changes on their bones.

At best, we're gonna improve 10 to 20% of their bone density that they've lost. And so I think the sooner we intervene the closer we can get to re maintaining the strongest bone density. Bone density in the long term. And so I think anytime somebody has osteopenia and we start to see them heading in the wrong direction, if we can reverse that loss and as the first study showed, really maintain that bone density, then for another 10 to 15 years we can really have a significant reduction on their future risk of fracture.

And that's really ultimately what we're trying to provide for patients.[00:13:00]

I think the second case is the one that's really gonna help us to sort of highlight that specific question related to fractures. All right. Now let's go into our second case. Alright. We have a 65-year-old female who was diagnosed with a recent forearm fracture at her osteoporosis clinic. She was found to, in fact, have osteoporosis with a DEXA scan revealing a T-score of negative 2.7 at the forearm.

She was also di diagnosed with primary hyperparathyroidism with a serum calcium of 10.5 PTH of 95 and a 24 hour urine calcium of 2 75, which is high normal. Her vitamin D was normal. She has no other comorbidities and no prior surgeries. So the clinical question here is is this patient.

Impacted by primary hyperparathyroidism and will parathyroidectomy decrease her risk of a future [00:14:00] fracture. This brings us to our third article. So our final article today was a practice changing article from Dr. Hayes Group at Kaiser in 2008, named effect of bone mineral density and parathyroidectomy on fracture risk in primary hyperparathyroidism.

This study from the World Journal of Surgery retrospectively reviewed 533 patients with primary hyperparathyroidism. T-score data. The study revealed that 30% of the study population had a parathyroidectomy while the other 70% were just observed. Patients with higher calcium labs were more likely to have undergone a parathyroidectomy.

And patients in the observation group were more likely to have osteoporosis patients who were offered parathyroidectomy. Had less fractures than patients who underwent surgery. Whether or not oh, sorry, than those who underwent observation, whether they had [00:15:00] normal bone mineral density, osteopenia, or osteoporosis.

In other words, the conclusion was that patients who underwent parathyroidectomy had a lower rate of fractures in the study than those who did not have surgery regardless of their bone mineral density. And so, you know, when we're talking about whether or not we need to wait for patients to have osteopenia or osteoporosis or whether or not we can intervene early, I think that this study.

Really kind of drives some of the point that Dr. Sippel was sort of commenting on from our own clinical practice where you really don't need to wait until these patients, you know, become osteoporotic. In hopes that then you're going to build back that bone mineral density because these patients start to you know, have a benefit over the course of those 10 years after surgery, even if they started with normal bone mineral density because they're having you know, less fractures.

You know, I mean, am I interpreting that the same way you would or do you have other thoughts? [00:16:00] Yeah, no, I, I think that you know, and there's other papers on this, but the way that I try to explain it to patients is that, you know, parathyroidectomy is never gonna restore your bone density to normal, but you're gonna improve by potentially 10 to 20% after surgery.

What we see is that the fracture risk reduction is actually greater than expected by the improvements in their bone density. And there are studies that show that that bone that you build back is actually really strong bone and is very fracture resistant. And so their risk of fracture really can return to almost normal or you know, and it doesn't necessarily correlate with their bone density after a year that their fracture is.

Reduction is much greater than we would expect based on their bone density. And the good thing is based on that first study that we talked about, is that that improvement in their bone density sustains for 10 to 15 years. So we're not just reducing the risk of fracture temporarily, but we're really providing a sustained impact on their bone [00:17:00] health.

You know, I gave a talk at the osteoporosis symposium at uw last year, and as I looked at all the data on the medical therapies for osteoporosis, parathyroid, the data on parathyroidectomy is so much better than all of the existing medical therapies for osteoporosis. It really has. The most sustained and profound impact in improving bone health in the long term for patients.

And so I think it's really important that we think about osteoporosis as a true indication for, for parathyroidectomy and to the point where we really need to be screening patients with osteopenia and osteo. For an underlying diagnosis of primary hyperparathyroidism. Because I do think that those patients would absolutely benefit from intervention and it's gonna be probably way more effective than any medical therapy that we're gonna be able to offer those patients.

And in fact, if they have an underlying diagnosis of primary hyper parathyroidism, the medical therapy may actually make things worse for them, not better. And so I think it's something that we [00:18:00] really need to educate our primary care. Providers to sort of think about this as a potentially one of the only correctable causes of osteoporosis.

Yeah, that's, that's a really good point. Dr. Sippel, and maybe we didn't mention this when I presented the first paper, but they actually, in that non-surgical group, they did have some patients that under that did have medical therapy and hyper therapy for osteoporosis. And at the 15 year mark, none of those patients showed any kind of significant long-term improvement in their bone density.

And I think some of the newer osteoporosis medications are such that even though there can be some short term improvements, as soon as you stop the medications, those improvements are lost and they actually get a rebound loss. And so again, the choice to go on medical therapy is really for many of these.

Patients a commitment to be on medication for life. And these are not inexpensive medications. And so I do think that in, in a comparison as far as both benefit [00:19:00] and, and cost, that Parathyroidectomy ends up being a much better option for many of these patients.

Very good. Reading through this third article did stimulate a few other questions. I was hoping Dr. Sippel could comment on. You mentioned that patients with higher calcium were more likely to get a parathyroidectomy. Why do you think patients with higher calciums are offered surgery more often than those with, you know, calcium, let's say 10.3, you know, which is kind of high normal for our lab as opposed to maybe 11.

I think when the disease is obvious, they're much more likely to get referred for treatment because the diagnosis is easier. If your calcium is 11 and you check a PTH and it's 200, everyone knows and feels very comfortable with the diagnosis. It's these mild patients, either normal hormonal or normal calcium that are harder to make that diagnosis.

But unfortunately sometimes those are the patients who've had the disease for the longest time period and have [00:20:00] had the most negative impacts. Both on their bone health as well as on their symptoms. I think sometimes the patients that I see in my clinic who have this relatively mild disease are actually the most symptomatic patients and the ones who potentially could benefit the most from surgery.

You know, I think part of this is educating providers about how to make this diagnosis and, and it's not always clear cut when they're mild disease, and so that's when sending them to a specialist, either a surgical specialist or an endocrinologist to sort of help clarify that diagnosis is important. I think the other thing to recognize is that oftentimes these patients who have mild disease tend to have negative imaging.

And I think unfortunately, that often happens where somebody thinks they have the diagnosis and they get some imaging and it's negative, so they say, oh, you must not have it, or You don't need surgery. And I think that that is not the case. When I think about patients with primary, hyper prepared thyroidism, I always think you have to make the diagnosis.

You have to be convinced that this is what it is. [00:21:00] You have to determine if there's indications for surgery. These patients with bone loss and fractures absolutely already have that indication. And then the localization studies are really just to help us to define what is the best approach to take for this patient?

Are they a candidate for a more focused surgery because they likely have an adenoma? Or do they really need a four gland exploration? 'cause they're most likely to have multi gland disease. And so really the imaging should never make your decision about whether to offer surgery. It really just helps you to plan what is the best surgical approach for this patient.

Yeah, I really appreciate that perspective. And I see the same thing in my own practice, where you look back on a patient who's been observed for several years and you realize that they had imaging previously from someone and it came back. N negative and therefore the patient was put back into a wing until, into an observation sort of, you know, trial until something else happened.

They had a fracture, they went from CKD three to CKD [00:22:00] four and then all of a sudden interest in surgical perspective, you know, gets reignited and that's. What spurs that, that surgical consult and I think a lot of endocrine surgeons see that. And I think these are just, you know, useful perspectives to sort of, you know, allow their surgeons to think about, you know, how we're looking at it and see how, see if they're experiencing something similar.

And I would say that a lot of times the first imaging test that's ordered by a primary care doctor is AIB scan. And I think that that's a historic gold standard for parathyroid localization. But I think most practicing endocrin surgeons have have evolved away and are not nearly as reliant on system I scans just 'cause their sensitivity just isn't that high.

Especially for these patients who have mild disease. It's good for picking up kind of obvious adenomas. But for mild disease, the, the yield is really quite low. I think in our practice, really ultrasound is our imaging of choice. We ultrasound every patient and I would. Say that, [00:23:00] you know, if you know where to look for parathyroid, you can find obvious adenomas in most patients with a good neck ultrasound.

And I would say that if the ultrasound is negative, occasionally I will order a system Bibi scan. But really my second line test if I feel like I need better localization is often of. Board, ECT scan. And, and partly the reason I do that is the reasons I would order it is if I don't have a good ultrasound, they have a big neck, their thyroid is really low lying, and I just really have limited views on ultrasound.

Or if they've had prior neck surgery and there's gonna be scar tissue. I think the 40 CT scan gives you better visualization of the structures deeper in the neck, as well as the upper mediastinum, which are the areas that you often miss with ultrasound. So I would say from a localization standpoint, I think ultrasound is probably the go-to for most surgeons.

And, and I think 40 CT scan has become oftentimes the second line for many patients. Yeah, that's a really good point. I had the [00:24:00] privilege to train with Dr. Sippel and so I did a lot of clinical ultrasounds and I use this primarily in my practice, and it also allows you to, to pick up potential thyroid disease.

If they've got thyroid nodules, you may pick up an incidental thyroid cancer or nodules. And so it's a great tool. And I just wanted to comment that this was a drive home point that Dr. Sippel taught me, and I tell this to the students I work with and even the patients, is that this is a biochemical diagnosis.

Imaging does not make the diagnosis. It's just it's a tool for the surgeon to plan their surgery. And it's a, it's a surgical planning tool, but it's a biochemical diagnosis. Yeah, absolutely. And I do think that the ultrasound is key, as you said. We're not that we're looking for thyroid nodules and thyroid disease, but you much rather know that there's a nodule in the thyroid that looks suspicious for a cancer ahead of time just because the thyroid and the parathyroid are directly adjacent to each other, and you'd much rather deal with it at the same [00:25:00] time.

And so, even though I'm an imaging minimalist, I require everybody to get a neck ultrasound because I don't wanna have a surprise. Finding of an unrecognized thyroid cancer at the time of surgery. If there's a nodule that's suspicious, I try to get it biopsied and so that we can plan thoughtfully about whether or not we wanna consider a concurrent thyroidectomy at the time of their planned parathyroid operation.

A lot of my practice is reoperations, and so I'm always trying to think about trying to prevent somebody from having a for gland exploration for their parathyroid disease now and then seeing me two years from now for their thyroid cancer diagnosis. I'd much rather deal with it both at the same time. I think that's better for the patient.

Yeah, that's a great point. So just for our listeners, Dr. Sipple then do, are you referring to ordering a thyroid ultrasound for patients to go to radiology, or do you simply just do the ultrasound yourself in the clinic and go from there? So for the most of my patients, I just do it myself in clinic as a screening test.

But I do [00:26:00] get a lot of patients who come from a distance for surgery. And since I'm not meeting those patients off until the day prior to surgery, I may not have time to do a biopsy then and get the information to guide my surgery. So I am getting that ultrasound locally to screen for thyroid nodular disease.

And I'm also, even though I'm not expecting the radiologist to find the parathyroid, if they actually capture cine clips of the neck, I can still review those ultrasound images and I may actually see the parathyroid on those imaging tests. So it also is helpful, I think, for patients to sort of get an idea if they have a massive goiter if they have you know, or their thyroid is really low line and the ultrasound's really limited.

Then I know that those cases are gonna potentially be more challenging. Those are cases where I may consider getting additional imaging with a four D CT scan or assessment, maybe scan.

Fantastic. Thank you for all the perspectives. I think our listeners probably learned a lot today and I appreciate everyone tuning in [00:27:00] for our journal club on primary hyperparathyroidism and the benefit. Benefit of Parathyroidectomy especially on the skeletal system, bone mineral density, and risk of fracture.

Thanks everyone and dominate the day I.