Dr. Lee is the chief of endocrine surgery at Columbia University Irving Medical Center. He serves as Co-Director of the multidisciplinary Thyroid Center, Parathyroid Center and Adrenal Center at Columbia.
Dr. Lee joined Dr. Hyesoo Lowe on an episode of Columbia Surgery’s podcast Conversations and Curbsides. (Click this episode link if you wish to listen). Their discussion explores whether sleep quality, brain function, and mood might improve after surgery in patients with primary hyperparathyroidism—a question that the endocrine team is currently researching. (Click here to learn more or join the ongoing study).
The following is a transcription of the discussion, and is lightly edited for context and clarity.
Jump to a Section:
- Stones, Bones, Groans & Psychic Overtones: Common Hyperparathyroidism Symptoms
- Sleep & Hyperparathyroidism
- Measuring Sleep
- Can Treating Hyperparathyroidism Help Sleep Disturbance?
- Going from Anecdotes to Data
- Potential Implications Down-the-Line
- Further Reading
Stones, Bones, Groans, & Psychic Overtones: Common Hyperparathryoidism Symptoms
Dr. Hyesoo Lowe:
Can you tell us more about the link that you're looking into between parathyroid disease and sleep?
Dr. James Lee:
Yeah, so it's really interesting. Every medical student learns that the symptoms of hyperparathyroidism, a high calcium level, high parathyroid hormone levels, are: stones, bones, groans, and psychic overtones.
And so “stones” refers to kidney stones. Obviously the “bones” are manifested as osteoporosis. The “groans,” some people get pancreatitis and other GI complaints. But the “psychic overtones” is really interesting.
A lot of patients who have hyperparathyroidism will complain of things like overwhelming fatigue. They get what they call brain fog, where their short-term memory is affected. And some people have difficulty with simple calculations. Basically, they just feel like their brain isn't functioning well. And there are a whole host of what we call “non-specific symptoms.” Currently, we just can't quite figure out why patients with parathyroid disease have those symptoms.
As you mentioned, if we can cure you with an operation, about 80% of those patients will feel better after the operation. It's 80% not a hundred because there are lots of reasons to feel tired and have some brain fog, et cetera. But the majority of patients do notice an improvement.
Sleep & Hyperparathyroidism
Dr. James Lee:
This is a long way of getting back to your original question about how sleep and parathyroid disease may be linked. So there's some evidence to suggest that patients with parathyroid disease actually suffer from worse insomnia than patients without. And so one of the things that we're looking at is whether there's a link between parathyroid disease and insomnia, which manifests as some of these psychic overtones or these nonspecific symptoms.
I don't know if you read this book, Why We Sleep by this guy named Matthew Walker. He is a sleep scientist at UC Berkeley. It's a fascinating book. Dr. Walker looks at the effect of insomnia and sleep disorder on all systems of the body. So what they've found is that there's lots of research to show that disordered sleep impacts cardiac disease, lung function, diabetes, weight, et cetera.
So one of the things that we're looking at is whether neurocognitive function is worse with disordered sleep. We're doing a cohort study where we're looking at patients who have parathyroid disease and comparing them to patients who have thyroid disease. We're looking to see how well their brain is functioning prior to the operation. And we're also correlating that with measures of how well they're sleeping.
Measuring Sleep
Dr. James Lee:
So basically there's this thing called “actigraphy,'' where we can figure out if you have disordered sleep. You basically put on a wristwatch that monitors your oxygen saturation and how many times you're moving during the night, et cetera, just to see the quality of your sleep.
We're asking them lots of questions about how they subjectively feel about how they're sleeping, called “Sleep Quality Studies.” And we're comparing those results with measures of cognitive function like short-term memory tasks. So an example of a short-term memory task is we give you 10 words to memorize. And then 30 minutes later, we ask you to repeat those words back to us.
Dr. Hyesoo Lowe:
Wow, things that are really hard to measure and that are sort of what we call soft symptoms, but not necessarily quantitative. So you're giving everyone an Apple watch or a Fitbit or what? Or is it more complicated technology for sleep measurements?
Dr. James Lee:
No. I mean, that's essentially what it is! It's a special watch called an actigraph, which just basically measures a lot of the things that the Apple watches will measure, plus some very specific things. But the theory is the same, right? Just as the Apple watch can measure how many times you get out of bed, how many times you wake up, and your heart rate and your vitals during a night of sleep, the actigraphy catches a lot of that as well.
The interesting thing is that there's a lot of really sophisticated backend interpretation of that data that we've partnered with our sleep experts in our sleep lab here at Columbia with.
Can Treating Parathyroid Disease Help Sleep Disturbance?
Dr. James Lee:
And so our hypothesis is that patients with parathyroid disease have a higher rate of disordered sleep. They're not sleeping as well. And their cognitive function is affected proportionately. And then when you fix their parathyroid disease, their sleep disorder improves, and their neurocognitive function or their brain function improves proportionately. And so we're using thyroid patients sort of as a control to see if it's really parathyroid disease that's really causing this problem.
There's some compelling data that was done maybe 10 or 15 years ago. There's a very small study out of MD Anderson, where they were looking at disordered sleep, through sleep questionnaires, et cetera. And they found that there seems to be a link, but they didn't have enough patients in that study to really determine that there was a correlation.
Dr. Hyesoo Lowe:
Fascinating. So I guess the first question is do people with hyperparathyroidism have worse sleep than people without parathyroid disease? So that's your comparison between the parathyroid patient and the thyroid patient who presumably has no parathyroid problem. (I hope the thyroid patients are not hyperthyroid because obviously they would have a disordered sleep).
So that would be question number one. That could explain a lot of some of these neurocognitive symptoms, which have to some degree been studied, that definitely patients have reported a lot more brain fog and other cognitive issues with hyperparathyroid disease.
And then I guess part two of this is the intervention, right? And so that's where the patient would serve as their own control because now you're going to look at them pre- and post-surgery.
Then you're going to compare the patient to the patient pre- and post their treatment. And that would be interesting to see—if they do have worse sleeping issues—do they actually get better?
Going From Anecdotes to Data
Dr. Hyesoo Lowe:
It's interesting that many patients sort of report those symptoms getting better. And we hear anecdotes every day. And anecdotes are great when you put enough together, but they don't really make science.
Having some actual data, because we are always data-driven in terms of everything we do, is extremely important. So it really helps to have a trial like this, to really be able to show a little bit more definitively that symptoms are not only stories, but they're actually things that we can quantitatively show get better. So that's very interesting.
Dr. James Lee:
You're absolutely right. There's actually some preliminary data to show that patients with parathyroid disease do actually have higher rates of disordered sleep or insomnia, and that's mostly done by sleep questionnaires.
The main issue that we've had with trying to figure out the relationship of parathyroid disease and these neurocognitive symptoms is that most of it is self-reported. It's just like people saying, "Oh yeah, I feel better," or, "I feel worse." But with this study, we're actually putting hard quantitative measures to it.
So with actigraphy we can monitor the quality of sleep in a very precise way. And then also we can measure the neurocognitive symptoms with this battery of tests that we do, which are very easy to apply. But to your point, it puts hard data to some of these measures that have just been subjectively reported previously.
Dr. Hyesoo Lowe:
Terrific. And when are you starting to recruit for this study?
Dr. James Lee:
We're recruiting right now.
Potential Implications Down-the-Line
Dr. Hyesoo Lowe:
Fantastic. And I don't want to overextend study results. But for example, if this link is confirmed, is it possible that people with these symptoms may kind of fall into a category where we offer them treatment maybe before they have other hard symptoms of the known criteria for surgery? I wonder. What do you think?
Dr. James Lee:
No, I think that's absolutely right. And actually that's a big part of this is that I think you've talked previously on the podcast before about what we call the classic indications for surgery, the hard indications, kidney stones, age, et cetera. And so many people feel like those guidelines maybe a little too restrictive, meaning we're not helping enough patients because they have sort of mild disease or they have these non-specific symptoms that you can't really quantify very well. And so our hope is that if we can really prove a correlation, that this will help more people get the treatment that they need at an earlier time point. So I think you're exactly right.
Dr. Hyesoo Lowe:
Hyperparathyroidism, a disease of many different angles. Thank you, Dr. Lee, for bringing us up to date with all of that.
Dr. James Lee:
Been a pleasure!
Further Reading
- Sleep & Cognition in Hyperparathyroidism Study | Columbia Surgery
- Parathyroid Center | US News Best Hospitals | Columbia Surgery