Summary
It’s a summer day and a 45-year-old is out for a drive. As she accelerates her stick-shift car, she starts to experience familiar, and scary, symptoms: facial tingling, numbness around her mouth, and a sharp pain in her hands. Her hands cramp and lock onto the steering wheel. Fortunately, she makes it home safely, but it will take many wrong turns and the help of Dr. Google to determine a diagnosis of hypoparathyroidism, a rare bone disorder. Dr. Michael Mannstadt, the Chief of the Endocrine Unit at Massachusetts General Hospital and Associate Professor in Medicine at the Harvard Medical School in Boston, shares this patient’s story and how a clinical trial changed this patient’s life.
Michael Mannstadt, MD
Michael Mannstadt, MD, is Chief of the Endocrine Unit at the Massachusetts General Hospital and Associate Professor in Medicine at Harvard Medical School, Boston, Massachusetts. His clinical and research interests focus on diseases of bone and mineral metabolism. He is particularly interested in hypoparathyroidism, and his NIH-funded research spans the basic, translational, and clinical realms of the disease. Mannstadt has served on numerous committees for the American Society for Bone and Mineral Research and the Advances in Mineral Metabolism and as Co-Chair of the International Workshop in Hypoparathyroidism and Primary Hyperparathyroidism. Mannstadt is an active physician in the Endocrine Associates Practice at the MGH, focusing on patients with disorders of mineral metabolism. He serves as a clinical advisor for the national patient group Hypoparathyroidism Association.
Transcript
DDx SEASON 10, EPISODE 5
The Bumpy Road to Hypoparathyroidism Diagnosis and Treatment
Dr. Raj Bhardwaj: This episode of DDX was produced in partnership with the American Society for Bone and Mineral Research and sponsored by Ascendis Pharma A/S.
Details of this case have been changed to protect patient privacy.
It’s summer in Boston. A 45-year-old woman is driving on the Massachusetts turnpike. As she accelerates to 70 miles an hour, she starts to experience familiar symptoms that fill her with dread.
Her face tingles, an unsettling numbness forms around her mouth. Sharp pain courses through her hands as they cramp up like claws and lock onto the steering wheel.
She’s driving a stick shift, a simple task that’s now become an impossible challenge.
This is DDX, a podcast from Figure 1 about how doctors think. I’m Dr. Raj Bhardwaj.
This season is all about the treatment of bone diseases.
Today, a case from Dr. Michael Mannstadt, the Chief of the Endocrine Unit at Massachusetts General Hospital and Associate Professor in Medicine, Harvard Medical School, in Boston.
Dr. Mannstadt has no financial or other relationship to Ascendis Pharma A/S. He has received no compensation for his participation in this podcast and the views represented are his own.
What you heard in our opening was how one woman’s unusual symptoms caused a routine drive to take an unexpected turn.
Prior to this incident, our patient’s symptoms were annoying, but not debilitating.
Dr. Mannstadt: She had some occasional crampings in her hands, numbness around the face and her lips, and that was going on for several months.
Dr. Bhardwaj: She went to see her family doctor.
Dr. Mannstadt: She told her physician and they didn’t quite know what to do with that.
Dr. Bhardwaj: Then she sought a second opinion.
Dr. Mannstadt: And she saw actually another physician who didn’t quite know what to do with that. She felt frustrated, obviously, that there was no diagnosis.
Dr. Bhardwaj: Without a diagnosis, she tried ignoring the problem, hoping it might resolve on its own.
Dr. Mannstadt: And so she was sitting in her chair and having these strange feelings, this humming feeling in her legs and her arms, and she was thinking, this is just my new normal.
Dr. Bhardwaj: But that day on the highway, when her hands cramped around the steering wheel, stubbornly resisting any attempt to change gears, she reached a tipping point.
Dr. Michael Mannstadt: She was afraid that something bad would happen, that she would have an accident, that she couldn’t control her car, and fortunately, nothing bad happened. She was able to stop her car. But at that point, she knew this is not normal. Something is totally wrong. She has to get to the bottom of that.
Dr. Bhardwaj: But without a physician to validate her concerns, she did what many patients do.
She turned to Dr. Google.
Dr. Mannstadt: In addition to Dr. Google, there’s Dr. Chat GPT and other AI helpers these days. And if one of the searches is for diagnosis and the computer produces a number of differential diagnoses, all it means is have you thought about A, B, and C. And especially in cases where we don’t have a diagnosis I find it helpful. You can easily say it’s not A, it’s not B, it’s not C, but D sounds interesting. Let me look into that. So I’m not opposed to that.
Dr. Bhardwaj: She went back to her doctor with what she’d learned.
Dr. Mannstadt: There were two diagnoses coming up. One of which was hypoparathyroidism. She had never heard about this and read about this and learned there’s something to do with her calcium. And so then she went to her doctor, saying, okay, look, I have these symptoms. We have to find the cause. And this is what Google tells me, please check on me.
Dr. Bhardwaj: Her doctor did the two standard tests for hypoparathyroidism: checking calcium and parathyroid hormone levels.
Dr. Mannstadt: A very low calcium was found which is typical for this disease and a low or undetectable level of parathyroid hormone, PTH, which is the cause of the disease causing hypocalcemia, low calcium levels. And so that made the diagnosis of hypoparathyroidism.
Dr. Bhardwaj: Hypoparathyroidism is when the parathyroid glands — tiny glands in your neck, which play a crucial role in regulating calcium in your body, aren’t working as they should.
When there’s a drop in parathyroid hormone levels, the body struggles to maintain the right balance of calcium.
People feel muscle cramps, twitching, and tingling sensations. It’s like your body’s sending out distress signals.
Fatigue, difficulty concentrating — they all become unwelcome companions in the world of hypoparathyroidism.
And since calcium is vital for nerve function and bone health, untreated hypoparathyroidism can lead to long-term complications.
Hypoparathyroidism can be a result of surgery, where the glands get inadvertently damaged or removed. Sometimes, it’s due to genetic diseases or autoimmune conditions, where the body’s immune system turns against its own parathyroid glands.
With some patients, it can be challenging to diagnose.
Dr. Mannstadt: I think that the rarity of the disease, the lack of a cause, and the symptoms that are somewhat nonspecific all contribute to some delay in diagnosis.
Dr. Bhardwaj: Once our patient was diagnosed she began the standard treatment: an oral calcium and vitamin D supplement, calcitriol.
But things didn’t improve for a couple of reasons.
Dr. Mannstadt: She didn’t really find a treatment option that was good for her. She had to take in the range of kind of six tablets a day. So it really is almost more than a nuisance for daily life.
Dr. Bhardwaj: Not only was this patient struggling to follow the prescribed dosing for her medication, the treatment itself wasn’t relieving all of her symptoms.
Dr. Mannstadt: The current standard of care, it does not replace the functions of parathyroid hormone. PTH keeps the serum phosphate levels normal, and it keeps also bone turnover normal. And all of these functions of parathyroid hormone are not replicated by us prescribing calcium and calcitriol. All we are doing really is by all means just increasing the serum calcium so that there are fewer symptoms of hypocalcemia, but we by no means can replace the functions of PTH.
Dr. Bhardwaj: Now, some people respond really well to this treatment, but unfortunately this wasn’t the case with our patient.
Dr. Mannstadt: She had these crises, hypocalcemic crises or crashes, what patients often call it. And what is that? You start a normal day and you feel like you have numbness around the mouth. Your face gets numb. When you talk, you feel like the muscles in your face cannot do really what they are supposed to do and feel differently. Your hands feel numb, you have muscle cramps, and you know it is coming. Really, all you can do at that time is to call 911 and go to the emergency room. And she had that several times. And the treatment of choice there is intravenous calcium as a bonus in the emergency room. And often patients and doctors don’t know why these crashes occur.
Dr. Bhardwaj: The other treatment option was parathyroid hormone replacement therapy. But because of the rarity of the disease and lack of resources put towards research, this form of treatment was only available in a clinical trial, which she participated in.
It changed her life.
Dr. Mannstadt: The advantage of this treatment is that you get back the actions of parathyroid hormone that are on many different organs, bones, kidneys, and indirectly on the intestine. And in the ideal situation we are able to almost normalize the biochemical constellation and the symptoms of patients.
She just had a normal life and with one injection a day. It worked really very well and her blood calcium normalized. Her urinary calcium actually normalized. So we were very happy on the electrolyte laboratory and for sure this changed her life for the better.
Dr. Bhardwaj: Let’s review some of the lessons from this case.
Our patient had to wait months before she was diagnosed with hypoparathyroidism.
Lesson 1: How might a delayed diagnosis in cases of hypoparathyroidism be avoided?
It sounds deceptively simple. And it comes down to the DDx.
Dr. Mannstadt: Always listen to the patient and if a symptom that is unexplained doesn’t go away after a certain time, then we have to look broader, right, every physician knows that. And certainly numbness around the mouth and the face and cramping of your muscles is a typical constellation for low calcium levels.
And our normal battery of blood tests that we often use to just check on the kidney function electrolytes contain calcium. And so you want to really look carefully for that and don’t dismiss even a slightly normal level at that time, because at other times of the day, it could be very low.
Dr. Bhardwaj: Lesson 2: What do you do when the standard of care isn’t cutting it?
Dr. Mannstadt: Treatment options that are not optimal, like the conventional treatment in hypoparathyroidism, it is much appreciated that patients, industry, and physicians make a concerted effort, actually, to develop new drugs and colleagues from all over the country are attentive to new trials and connect patients with the centers that conduct these clinical trials.
In those patients who have had a hard time with conventional therapy and now finally get the PTH replacement, you see already when the patient comes in, that they are happy and that they talk more about their family and their normal life than about the calcium and magnesium. Some of the patients tell me they even forget that they have hypoparathyroidism.
Dr. Bhardwaj: Thanks to Dr. Mannstadt 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.
Head over to figure1.com/ddx where you can find full show notes, speaker bios and photos.
This episode of DDX was produced in partnership with the American Society for Bone and Mineral Research and sponsored by Ascendis Pharma A/S.
Thanks for listening!