Transcript: 3 Simple Steps for a High Calcium Workup (Plus, Do-Not-Miss Diagnoses)

​Liz Rohr:
Well, hey there, it's Liz Rohr from Real World NP and you're watching NP Practice Made Simple, the weekly video series to help save you time, frustration and help you learn more faster so you can take the best care of your patients, because that's what we all want, right? So today I want to talk to you about high calcium. I know lab interpretation as a new grad is really confusing. It was for me, and it's definitely coming up as a topic for a lot of new grads that I've talked to. So I want to focus on calcium today, high calcium, and really break it down into three simple steps of investigation and workup. And I'm going to do it by using a case study, a really interesting case study of my first year. A quick note is that I want to keep it interesting, concise, and brief because I know that you're really busy.
 

So it's a little bit of a longer video today, but I've really kept it straight to the point without any fluff. So I hope it's really helpful. One more quick note is that it is a case study and patients are not one-dimensional, so that there are many moving parts to this case. I'm really going to focus on one aspect of it and touch on some of the other management aspects. If there's a topic in particular that you want to hear more about, definitely leave me a comment below with the topic or question that you have and hopefully I've made it as clear and concise as I can. So without further ado, I'm going to share my screen with you.
 

All right, so let's get started. So this is the hypercalcemia case study. We're going to start with Laura. She's 36 years old, she's a new patient to the clinic. The PHI, Personal Health Information, has been removed. This is not her real name or her photo. She's a little too happy, unfortunately, based on her clinical scenario. But no that is not her. So Laura is a 36-year-old female, new patient to the clinic. She's there to establish care. She has never been there before. She's coming from a different clinic. She got her healthcare at a different clinic a couple years ago. So she's actually here for an ER follow-up. She had a DVT and it's her first one she's ever had. She's on a Lovenox bridge until she's therapeutic with her coumadin, with a goal of INR 2-3. If you don't know what a Lovenox bridge is or you haven't heard of it before, it's when patients will get Lovenox and coumadin at the same time until their INR is in within goal and then you stop the Lovenox bridge.
So she's a former smoker. She smoked half a pack a day and she just stopped. She was a little scared by the DVT I think. So she's taking Queen Anne's Lace herbal supplement for contraception. So this was actually the first time I've heard of this and it's not common at all. This is her words. I've never seen any recommendations about this. I could say a lot of things about this, but let's stay focused for today, her past medical history is only significant for a therapeutic abortion a few years ago. No past surgical history, family history, that she knows of. And she's sexually active with one male partner and they're monogamous. And she's a working professional. She works a nine-to-five job.
 

So the plan, we're going to check her labs, we're going to check that her INR is therapeutic or not and see if she can stop that Lovenox. We're going to check a CBC today because we don't have any labs from the hospital and we want to get a baseline hematocrit and hemoglobin because of the risk of bleeding for coumadin. And I'm also going to get a CMP for her because I want to get her baseline renal and liver function. Most likely it's normal because she's presumably a healthy 36-year-old female aside from this DVT. But it's important to check that, and I didn't have any records from the hospital. So today I'm going to focus on hypercalcemia specifically, but I'll touch on the other components of holistic care at the end, because clearly we're not just focusing on one thing when we're with a patient.
 

So here are her lab results. Surprise her calcium is high. You probably saw that coming. So right here... Oops, I'm going to get my little points are going. So right here is going to be the BMP, basic metabolic panel. You've got your renal function, calcium is high, carbon dioxide, creatinine, GFR, renal function is normal. I spliced it over here with the abbreviated CBC, because I wanted it to fit all on one slide. But her potassium's normal, her sodium is normal. Hematocrit and hemoglobin also baseline normal, so it's a good thing in case later we check it and it's lower, she could have a risk for bleeding somewhere because of the coumadin. So platelets are normal. White blood cells are normal. Her INR is showing up as abnormal at 2.1 because it's greater than the expected 1.1, but it's actually normal for her as you saw before. We're looking for a goal of 2 to 3 for her coumadin.
 

And another note is that her hepatic panel is also normal. I didn't include it, again because I wanted it to fit on one slide, but her albumin, her protein is normal at 3.7, which will be important in a moment. So for hypercalcemia, I want this to be really easy. I want it to be the three steps that you automatically think of when you see a high calcium level. So step number one, is it truly high? So calcium is bound to protein and so you need to correct for the albumin level. So if you have low albumin, you're going to have a superficially low calcium and vice versa. If you have a high albumin, you're going to have a higher calcium level, which is not necessarily concerning. So you're going to use a calcium correction calculator. On the ultimate resource guide, there's MDCalc is one of the apps that you can download or you can just Google it and see what the actual corrected calcium is.
 

And then the other thing, the expert opinion based on no randomized controlled trials, but expert level of evidence, and this is kind of consensus. I see this all the time and I recommend it as well even though I'm not super fond of that level of evidence. It's not as strong as a meta-analysis of course. However, it's recommended to repeat the test and make sure to confirm that this calcium is truly high with another repeated BMP with the albumin or a complete metabolic panel that includes the albumin. Or you can repeat it with an ionized calcium, which is a little bit more of a specific test if that's available with your laboratory. It's not in my current clinic unfortunately, but I have used that in the past. So step one, is it really high? You rechecked it, you confirmed it, it is actually high.
 

Number two is, how high is it? And it's actually not quite number two because you have to think about this at the same time as step number one of the, is it truly high? Because if it's super high and it's the first lab, I'm going to be more concerned about that and I'm probably not going to wait to recheck it depending on the picture. So just stick with me for a second. So how high is it? So the normal range for calcium, and this is dependent on your laboratory, but typically it's 8.3 to 10.3. So if it's greater than 14 with your calcium correction score or you did an ionized calcium and it's greater than 10 and the normal for that is up to 4.9, and/or they're symptomatic, they need to go to the ER because that's really concerning. We should correct that pretty quickly with some IV fluids. And a quick reminder about symptoms of high calcium, that's confusion, feeling thirsty all the time, peeing all the time, dehydration, lack of appetite, nausea, muscle weakness, a little bit vague symptoms, but something to think about.
 

So is it truly high? How high is it? Is it less than 14? And is it confirmed that it's actually a repeat true high score with the corrected calcium score? And then two causes. So pretty easy here, right? So 90% of all cases, more than 90% actually are going to be from two different things. 90%, number one is going to be primary hyperparathyroidism, that's just across the board, that's going to be your number one. And number two is cancer. So that's really concerning. So you should really not dismiss high calcium. 90% hyperparathyroid and cancer. Really pretty easy. Three steps and the top two diagnoses.
 

So what's next? For her, we've determined it's safe to do an outpatient workup because, again, the first check, it was less than 14 and she had a normal albumin, no symptoms. We called her up on the phone the next day when we got the result and she wasn't having any of those symptoms. Regardless I'm going to advise her of high calcium precautions, and that's staying hydrated, avoiding prolonged bed rest, which I'm not really concerned about because she's ambulatory, she works, she's a working professional, she's not bed bound, she's not wheelchair bound. And avoiding a super high calcium diet, which is a little bit hard to quantify, but if you can do a quick ask of, "You know what, are you chugging gallons of milk per day or other high calcium foods?" That can hopefully be helpful.
 

So a quick med check. This is a quick win in terms of for high calcium, does she take any thiazides or lithium? Which we know in this case she doesn't. We've done a med rec when she first arrived to the clinic. But hydrochlorothiazide, tons of people take, and chlorthalidone as well. And lithium, depending on your patient population, I used to see a ton of lithium. So if you see lithium, that's definitely something to think about.
 

So we're going to start her workup because it's safe to do outpatient. So hyperparathyroid is going to be the very first one because it's the most likely cause. So you're going to start by ordering an intact PTH. The cancer workup, most common cause number two, you're going to start that after you rule out the hyperparathyroid because it's just less common and the labs are a little bit more involved. Most of the time in terms of reassuring you that you're not staying awake at night thinking this person has cancer and that you're missing it, most of the time calcium is going to be on the higher side, like a 12 or a 13, and it's also going to be an acute increase and it's not going to be chronically high. And a note about acuity, if someone is has acutely high calcium, they're more likely to be symptomatic than someone who has chronically high calcium, in the case of chronic hyperparathyroidism that hasn't been detected in a while. So don't worry about her, it's okay.
 

So other causes, I do not want to overwhelm you by listing these, but it's important to know because it's relevant to the workup. So if you can just start by keeping in your mind the cancer and the hyperparathyroidism, here are some other causes, and it's going to make sense in a second when I show you the algorithm. So granulomatous diseases, lymphoma and tuberculosis, not very common, but they can cause it. Vitamin D toxicity, if someone's taking a ton of a vitamin D supplement, that's really important that you do that supplement med rec when someone comes in. If they're taking over-the-counter things, you're kind of getting that out of the history. Multiple myeloma, in my mind I lump it in the cancer category. It's a neoplastic process and it's a little bit complicated, but kind of a topic for another day, but keeping in your mind that it's a less common cause. But it'll be relevant in the second I'll show you.
 

And then hyperthyroidism. If you have a hyperactive thyroid, you can get high calcium. Medications again, thiazides and lithium are the most common causes. There's a couple of other ones that are pretty rare. So if you have a patient who has rare medications, like Forteo is one of them, which is that injectable osteoporosis medication. The other one, I have never seen it before. So weird meds, double check the side effects. Uncommon meds, I should say, not necessarily weird. And other endocrine hereditary abnormalities, but this is outside the scope of primary care. So if you've done your workup and you're getting to this point, they definitely need... In my mind that's fine. I don't even need to remember the names of those things because they're going to be going to an endocrinologist and I've done my job as a primary care provider, and doing the initial workup and labs for safety.
 

So here's the algorithm. I really don't want to overwhelm you, but I'm such a visual person that I find this really helpful. And if you're listening to this instead of watching it, hopefully I can go slow enough that it makes sense. So number one, just reiterating again, we're going to confirm that it's hypercalcemia. Step number two is we're going to check the intact PTH. And if it's high, that's one way, you're going to evaluate that further. Or if it's low, and I have a star asterisk there because on the next slide, I'm going to get into that in one second, just a little note about PTH. If it's low and it doesn't seem like a type of parathyroid, you're going to move on to that cancer and other cause workup. So this is based on the UpToDate algorithm, which is congruent with the other resources that I found. So PTHrp is PTH-related peptide or protein, which is related to kind of a neoplastic process.
 

Vitamin D 25 is the active form of vitamin D and vitamin D 1,25 is the inactive form, which is relevant in just a sec, hold on, stick with me. And then the next step after that is to check the SPEP and UPEP and free light chain assay, which is that kind of bottom step where you're moving towards the multiple myeloma. So that's kind of a lot of information, but just stick with me for one second.
 

So we're going to move to the workup for this particular patient, Laura. Her calcium is 11.5. So number one, again, order intact PTH. If you only take one thing away from this is just don't ignore a high calcium and check a PTH, step number one. The really important note here that I want to make is that the normal range is 10 to 60. And I'm sorry I left off the markers, the units of measurement here, but UpToDate algorithm, which also agrees with other sources, is that mid to upper normal range is also considered to be abnormal, so 35 to 65, even though technically it's only elevated above 60. So don't ignore that. So when you're going through your labs and you're looking through the PTH, don't just scroll over it because it's not a bright red color or a bolded abnormal range. It's still important to pay attention to the actual number. And you can look up that reference range. I look it up every single time.
 

So for this patient, I order the intact PTH, the vitamin D, and the TSH. And I know I just said that the most common causes are the PTH and then cancer. So why am I ordering things that are farther down the line? And my kind of a real world point here is that as a primary care provider, I'm going to order the tests that I can do something about in the clinic. But vitamin D and TSH are also just quick wins. Let's just make sure it's not that, because the other labs are kind of involved. The PTHrp, I did not order that at the time and I did not feel comfortable ordering that. Again, the 1,25-OH and SPEP, UPEP, free light chain assay, I think four years in and having an internal medicine physician that I work with, I'd feel much more comfortable ordering those. But for this patient, in my first year of practice, I ordered those first three to start.
 

And the other note about that is that because she's a working professional... I'm going to go back real quick. So if you're looking at this management algorithm, it says step one, you check the calcium, step two, you check this lab, step three, you check this lab. Step four, you check... That's a lot of times to come back and get some labs drawn. So for this patient, I just kind of lumped them all together because number one, I don't want to lose her to followup, because I work in a federally qualified health center and a lot of my patients have kind of tumultuous lives and it can be very hard for them to get to the clinic. And I also just don't want to lose her to follow-up, and I want to make patient-centered care, holistic care. I want to make sure that she's not getting stuck three different times and that she's able to get the good care that she needs.
 

So those are my real world notes about that, is that personally I started with the intact PTH and vitamin D and the TSH. Now as a more established primary care provider with supportive supervision, I feel like I could also order that, but I probably wouldn't order that right away. I'd probably batch it into two different blood draws just to kind of conserve resources and based on the likelihood.
 

So results, here are her results. So I rechecked the ionized calcium at the same time instead of doing a recheck and then coming back again. Ionized calcium at that time was still elevated, so it truly was a high calcium. Her intact PTH is 59. Her vitamin D is 40, which is normal. TSH is normal. But yeah, note here, high normal. So she still needs a workup even though it's technically within the normal range.
 

So let's go back to Laura. She is looking happy still, but she was not at the time, she was a little bit worried and concerned, and I was too. But step one, I referred her to endocrine, because at that point the testing that she needed for a hyperparathyroid workup, I didn't even have access to the type of labs that she would need to do. And so that's an easy place to draw a line as a PCP in terms of specialty versus in-house. And I'm certainly not going to do the treatment for it. And hyperparathyroid is its own topic, so I'm not really going to get into that right now. But refer to endocrine. And in terms of her other holistic care, because she came there originally for the DVT, I'm going to stop her Lovenox because her INR was therapeutic. I'm still going to manage her coumadin in-house, and you might not necessarily do that at your clinic, but I've got a great algorithm for management if you are interested in looking at that. Some people go to coumadin clinics, but it really depends.
 

So smoking cessation, reinforcing, she's already stopped, but we're going to continue, "That's probably related to your DVT." We talked about contraception and that I didn't really recommend her to do that. Not high levels of evidence, but anyway, longer discussion for another time. Heme referral. So I was pretty uncomfortable at the time, and I'm getting more comfortable in terms of DVT and blood clot management. There's a topic with blood clots of whether this is a provoked or unprovoked DVT and that determines how long you need to take coumadin for. And I didn't feel comfortable with it at the time, so I had her see hematology. I probably would feel a lot more comfortable with that now. So at the time I had her follow up with me in a month, and then three months after that just to kind of make sure that she was still feeling okay, things were going well, and she was able to get connected to the specialist that she needed to go to the endocrine [inaudible 00:18:15].
 

So that's it. Leave me a comment below. I'd love to hear from you. What is the number one takeaway that you've had from this presentation? Hopefully rechecking your calcium and checking your PTH. But yeah, definitely leave me a comment below.

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