A 23-year-old presents to the emergency department with progressive symptoms. It starts with tingling in the fingertips that lead to leg cramps that turn into feeling like she’s turning into stone, frozen in one position with stabbing pain. And perhaps most troubling, she can’t concentrate. In fact, the brain fog is so severe that she’s afraid to drive.
Over the course of three days, her life has been turned upside down.
She takes a taxi to the emergency department and is seen after waiting six hours. She provides a quick medical history, noting she recently had neck surgery for parathyroid overactivity — an important clue to her diagnosis.
Parathyroid glands produce parathyroid hormone that regulates the blood calcium level, which maintains bone strength and helps muscles and nerves function. Calcium levels in the blood have to be kept at a very specific level. Just like in your physiology lectures: HYPERcalcemia and HYPOcalcemia. And calcium levels that are either too high or too low can be deadly.
But in moving quickly in the emergency department, testing for serum calcium is overlooked. A patient with recent neck surgery has symptoms consistent with low blood calcium levels — why not check her calcium?
It’s true that in a chaotic ER things can be overlooked. But a lot of time, calcium isn’t ordered because it’s not part of the regular “electrolyte” or “chemistry” panel — it has to be added specifically. With computer systems and the way test panels like these are built, they can shape the thinking of physicians, putting certain symptoms front of mind, while others might get neglected.
Fortunately, a diagnosis was caught early enough for this patient that no long-term damage was done. But this case serves as a reminder that although rare diseases are rare, it doesn’t mean as a healthcare professional, you’ll never encounter them.
Bart L. Clarke, has been compensated by Ascendis Pharma for his participation in partnership with The American Society for Bone and Mineral Research.
Bart L. Clarke, M.D. is Consultant and a member of the Metabolic Bone Disease Core Group in the Division of Endocrinology, Diabetes, Metabolism, and Nutrition at the Mayo Clinic, and Professor of Medicine in the Mayo Clinic College of Medicine. His current clinical research interests include parathyroid disorders, postmenopausal osteoporosis, and glucocorticoid- and transplantation-induced osteoporosis. He is Past-President and a former Council member of the American Society for Bone and Mineral Research, and a member of the Endocrine Society, American Association of Clinical Endocrinologists, and the American College of Physicians. He is on the Editorial Boards of Osteoporosis International and Journal of Bone and Mineral Research, and a chair of the Mayo Clinic Institutional Review Board.
DDx SEASON 6, EPISODE 2
Overlooked Diagnostic Test for Blood Calcium Levels Leads to Rare Diagnosis
RAJ: A 23-year old woman presents to the Emergency Department with progressive symptoms….
It started with tingling in her fingertips… she didn’t think much of it…
Then she’s woken from sleep by leg cramps… cramps which eventually spread to her hands.
She feels like they’ve turned to stone, frozen in one position with stabbing pain. Her entire body hurts…
And perhaps most troubling, she can’t concentrate. In fact, her brain fog is so severe that she’s afraid to drive.
Over the course of three days, her life has been turned upside down.
RAJ: This is DDx, a podcast from Figure 1 about how doctors think.
I’m Dr. Raj Bhardwaj.
This season is all about rare bone diseases.
Today, a case from Dr. Bart Clarke, an endocrinologist at the Mayo Clinic in Rochester, Minnesota, who specializes in bone and calcium disorders.
CHAPTER 1 – MISDIAGNOSIS
RAJ: Our patient took a taxi to the ER.
Dr. Clarke: She went, she waited for about six hours before she was seen.
RAJ: And her symptoms didn’t let up.
Dr. Clarke: During that time she was having active symptoms, muscle cramps, and she had tingling in the fingertips, the toe tips, the lips, the nose tip with associated muscle cramps.
RAJ: When she was seen by the ER doc, she quickly gave her medical history.
Dr. Clarke: Many patients who come in like this on a busy ER, afternoon or evening, you get two minutes to tell ’em what’s wrong with you. and of course, sometimes things get overlooked.
RAJ: And with that medical history was an important clue to her diagnosis.
Dr. Clarke: She had just undergone neck surgery for parathyroid overactivity.
RAJ: We all have parathyroid glands.
Dr. Clarke: In the front part of your neck, just at the hollow of the base of your neck, above collarbone level.
RAJ: They’re about the size of a grain of rice.
Dr. Clarke: And there’s four of them. There’s two on the right, two on the left.
RAJ: Parathyroid glands produce parathyroid hormone that regulates the level of calcium in the blood, which maintains bone strength and helps muscles and nerves function.
As you might have guessed, calcium levels in the blood have to be kept at a very specific level.
Remember your physiology lectures? The classic constellation of HYPERcalcemia – too much calcium – is “bones, stones, groans, and moans”…
Painful bones, kidney stones, abdominal groans (belly pain, constipation) and psychiatric moans (lethargy, fatigue and memory loss)…
HYPOcalcemia is equally dangerous… with the classic constellation of CATS – Convulsions, Arrhythmias, Tetany, and Spasms, seizures, and stridor…
Calcium levels at either extreme can be deadly…
But back to our patient.
At this point the ER doc was thinking about the differential diagnosis.
Dr. Clarke: And so the other things that we think about that could cause these symptoms would include low sodium, low potassium, low magnesium, low phosphorus. And so in this particular population, we think about iron overload; people who cannot not reabsorb iron. They absorb a lot of iron. They store this in the parathyroid glands and other tissues in the body and the glands malfunction. So that was one possibility too. And so laboratory testing was sought to clarify what was going on.
RAJ: But there’s one thing they didn’t test for.
Dr. Clarke: They tested her for other things, but not for serum calcium, it turned out.
RAJ: Now, you might be wondering, what were they thinking?
A patient with recent neck surgery has symptoms consistent with low-blood calcium levels – why not check her calcium?
It’s true that in a chaotic ER things can be overlooked.
But a lot of time, calcium isn’t ordered because it’s not part of the regular “electrolyte” or “chemistry” panel – it has to be added specifically.
The computer systems we use and the way test panels like these are built can shape our thinking as physicians, putting certain symptoms front of mind, while others might get neglected.
In the meantime, our patient was sent home.
Dr. Clarke: As oftentimes happens when they’re not sure they’ll tell you to maintain hydration, drink plenty of fluids. Try not to overdo things, try not to exert yourself too much. To let time sort things out and see where things are gonna go. They didn’t give her any specific treatment because they hadn’t recognized what was going on.
RAJ: But the next morning she was back in the ER with symptoms that hadn’t improved.
CHAPTER 2 – DIAGNOSIS
Dr. Clarke: In her case when she went back the next morning things were less busy and they spent more time with her and discovered all these other things that led them to say, maybe it’s the calcium. They finally did test the serum calcium.
RAJ: And some additional tests were conducted as well.
Dr. Clarke: Calcium phosphorus. Kidney function. And because she had just undergone neck surgery for parathyroid overactivity, she actually had parathyroid hormone measured in her blood.
RAJ: The results now pointed to a clear diagnosis.
Our patient was referred to Dr. Clarke for treatment.
Dr. Clarke: We looked at the labs that they had done and because of that, we could tell pretty clearly what had been discovered. It turned out that the calcium was low, the phosphorus was high and kidney function was normal. she had no circulating parathyroid hormone to keep her blood calcium normal. So clearly she was deficient in parathyroid hormone.
RAJ: The fact that she’d recently had surgery made the findings even more conclusive.
Dr. Clarke: In this setting with these kinds of findings post-surgery it was very clear that she had developed post-surgical hypoparathyroidism.
RAJ: This is actually the most common form of hypoparathyroidism.
Dr. Clarke: So of all the people with hypoparathyroidism in the world right now, it turns out that about 75% of patients have a postsurgical cause for their hypoparathyroidism.
when I see a patient the very first time, and it’s not clear why they have it. The first thing I do is look at the anterior neck. And if in the front part of the neck, there’s a clear scar then usually it means they’ve had maybe thyroid cancer, thyroid nodule head or neck cancer sometimes, or even sometimes parathyroid overactivity that was treated by surgery. And they just went too far the other way. So that’s how we find out.
This case describes what we see periodically where patients have surgery. They only take out one gland and simply the manipulation of the structures in the neck during surgery is enough to make the three other glands fall asleep essentially and not wake up. And this is what turned out to be the case for her.
RAJ: The parathyroid glands can “fall asleep” temporarily because of changes in the blood supply to the glands, or just moving the glands around during surgery.
And as you might have guessed, once those glands fall asleep, they stop producing PTH, which significantly decreases the amount of calcium in the blood.
Which is what brought our 23 year old patient to the ER.
Dr. Clarke: Most patients complain exactly of what she had tingling in the fingertips, the toe tips, the lips, or sometimes the nose tip with associated muscle cramps. But most of them also tell us that they notice brain fog. They can’t think straight. They can’t remember things. Many of them say I can’t drive my car. I can’t go to my job and function because things are just not connecting. And it turns out all of these things tend to be mostly due to the low calcium in the blood. And typically this will not resolve until intravenous calcium is given at the emergency department.
RAJ: If left untreated…
Dr. Clarke: The body compensates by essentially taking calcium from the bones, putting it into the blood.
RAJ: Eventually bones become weak, kidney stones can form and the heart and brain can be affected.
But luckily things for our patient didn’t progress that far.
Dr. Clarke: We gave her a recommendation for something called calcitriol. That’s an active form of vitamin D that directly stimulates intestinal absorption of calcium. So that was a very key part of this calcium alone in this situation sometimes works, but many times doesn’t work very well. And so this is why the calcitriol and vitamin D are added in her case because her magnesium levels were normal.
RAJ: Post-surgical hypoparathyroidism usually isn’t a permanent condition.
Dr. Clarke: In her case, it’s well known that these glands after surgery can take as long as a year to wake up. It turns out. And in her case, fortunately, about nine months later, the three remaining glands woke up.
RAJ: And once they did, our patient’s calcium levels began to stabilize.
Dr. Clarke: And with that, her blood calcium actually increased and so over time it became evident that she wasn’t gonna need long term conventional therapy or that she would need parathyroid hormone treatment that could be given if she had never had recovery.
CHAPTER 3: LESSONS
RAJ: Hypoparathyroidism is uncommon – but that doesn’t mean you won’t encounter it as a care provider.
Dr. Clarke: Lots of people have this where it’s never clinically recognized. So when a patient comes in and has symptoms of muscle or nerve dysfunction, tingling, paraesthesia in the fingertips and muscle cramps or tetany clearly calcium should be one of the things that’s checked routinely and along with these other things and whatever else the patient might have. Those things can be looked for too. But keeping calcium and PTH in mind, especially with an anterior neck scar that won’t stir you wrong I don’t think anytime.
RAJ: Thanks to Dr. Bart Clarke for speaking with us.
This is DDx, a podcast by Figure 1.
Figure 1 is an app that lets doctors share clinical images and knowledge about difficult to diagnose cases.
I’m Dr. Raj Bhardwaj, host and story editor of DDx.
You can follow me on Twitter at Raj BhardwajMD.
Head over to figure one dot com slash ddx, where you can find full show notes, photos of classic findings of hypo- and hyper-calcemia, speaker bios and links to similar cases.
This episode of DDx was produced in partnership with The American Society for Bone and Mineral Research and sponsored by Ascendis Pharma.
For more information on hypoparathyroidism please visit Ascendis Pharma dot com
Thanks for listening.