This transcript has been edited for clarity.
Kaniksha Desai, MD: Welcome to another episode of the Thyroid Stimulating Podcast, which is created in conjunction with the American Thyroid Association to discuss up-to-date diagnosis and management of thyroid diseases. I'm your host.
Our thyroid gland plays a crucial role in regulating many bodily functions, including metabolism, energy levels, and even our sleep patterns. Whether you're dealing with hypothyroidism, hyperthyroidism, or are simply curious about how this small thyroid gland impacts your nightly rest, this episode is for you. We'll explore how thyroid imbalances can lead to sleep disturbances, such as insomnia, and how poor sleep quality can impact your thyroid gland.
Joining us today is Dr Skand Shekhar from the National Institutes of Health (NIH). He completed medical school at the University of Delhi in India, completed a master of health sciences at Duke University School of Medicine, and went on to complete clinical and research training and an endocrinology fellowship at the NIH, focusing on reproductive endocrinology.
His research involves studying the interaction between lifestyle, sleep, diet, and the hypothalamic-pituitary-gonadal/hypothalamic-pituitary-adrenal axis in humans. He is developing clinical trials to enhance our understanding of sleep metabolism and reproductive endocrinology interplays. He's here today to discuss the interactions between the thyroid gland and your sleep.
Skand Shekhar, MD, MHS: Thank you very much, Dr Desai, for inviting me to your podcast. I'm happy to be here and excited to talk about this important topic. Before we move any further, I do want to clarify that everything I say today reflects my personal views. I do not speak on behalf of the NIH or the US federal government.
Desai: How did you get interested in this topic?
Shekhar: That's a good question. I have a deep-rooted interest in neuroendocrinology and its interaction with our environment. Inevitably, sleep is at the center of this interaction, which integrates things like puberty onset, growth hormone secretion, and, of course, a number of metabolic disorders that tend to have an association with sleep.
Therefore, it was natural to think about the thyroid and how it is related to sleep, which really sparked my attention. In addition, from a clinical factor standpoint, we also see that many patients who have thyroid problems tend to also complain of sleep issues. It was a natural subject that piqued my attention, and I decided to delve deeper into this topic.
Desai: Speaking of that, I know that many thyroid patients have sleep problems, and many sleep problems can cause thyroid problems. How common of an issue is this?
Shekhar: It's a fairly common issue. I'll try to answer this question by breaking it up into individual issues. First, as far as hypothyroidism is concerned, it's a widely prevalent issue. In fact, the NHANES data published a few years ago demonstrated a steady increase in the rates of hypothyroidism such that it has doubled from the estimate of about 5% in the late 1990s to approximately 10% in 2019. It tends to impact women disproportionately. Similarly, hyperthyroidism is also a common problem, although not as common as hypothyroidism, and it affects about 1% of the general population. Again, women are more widely impacted.
In terms of sleep problems, the CDC has released data that indicate that 15% of the adult population tends to be impacted with one or more sleep problems. That, again, tends to be more common in women, where about 17% of women have sleep problems compared with 11% of men.
As far as the overlap of both of these problems is concerned, there's not a tremendous amount of data. The available data are indirect. There was one important study that showed that 1 in every 4 people who had hypothyroidism were affected by obstructive sleep apnea. Similarly, there is no reason to believe that sleep problems will be any less common in patients who have hyperthyroidism. Certainly, those of us who see patients with hyperthyroidism could attest to this issue. It's clearly an important issue that affects a significant percentage of our patients.
Desai: I want to get into the physiology and the pathophysiology behind that. What are some of the underlying mechanisms by which thyroid hormones influence sleep patterns and sleep quality?
Shekhar: Let's start with circadian clocks. Circadian clocks are internal timekeeping mechanisms that regulate many physiologic functions in humans. These endogenous clocks are integrated at the level of the suprachiasmatic nucleus and the pineal body, and they create oscillations for a 24-hour period, which is what we call the circadian rhythm.
Thyroid hormone secretion has a distinct daily rhythm, and it is heavily influenced by the circadian rhythm such that thyroid-stimulating hormone (TSH) has a distinct day/night pattern. As an example, TSH levels are lowest between 3:00 in the afternoon and 7:00 in the evening, and they tend to be the highest between 11:00 PM and 5:00 AM.
For circulating thyroid hormones, the data are a little less clear, but the most robust studies done to date, by Gundersen and colleagues and Russell and colleagues, have demonstrated, again, a clear diurnal circadian pattern of triiodothyronine (T3) and thyroxine (T4) secretion such that free T3 rises by about 15% and free T4 rises by about 11% at nighttime. It's also interesting to note, but not that surprising, that these peaks tend to be shortly after the peak of TSH, and there's a time lapse of about 90 minutes or so.
Multiple studies have demonstrated that there is a close relationship between sleep and thyroid hormone secretion. This is partly influenced by the circadian rhythm, but it's also independent of that rhythm. To give you an example, restful sleep, or what is called slow-wave sleep, decreases the amplitude of circadian TSH secretion and also of circulating active thyroid hormones. It has been suggested that lower TSH and thyroid hormones, in turn, are permissive for what is called slow-wave sleep, or restful sleep, and maintenance of normal sleep architecture.
I think it's safe to say that sleep quality and architecture also influence TSH secretion, and this association tends to be bidirectional such that decreased slow-wave sleep can negatively impact thyroid hormone secretion and vice versa.
Talking a little bit more about the active thyroid hormone, namely free T4, it has been proposed that the widely reported increase in T4 levels in response to sleep deprivation is actually a physiologic adaptive mechanism. Thyroid hormones tend to upregulate mitochondrial numbers and also increase their function. This is to thyroid hormone receptors present in neural mitochondrial membranes. One could easily understand that in the setting of increased energy demand, there is an increase in the number of mitochondria, which is able to produce extreme levels of adenosine triphosphate (ATP) that can keep up with that neuronal energy demand.
The final piece of this puzzle is dopamine. Many of you in the audience may already know that dopamine inhibits prolactin secretion and also inhibits TSH and thyroid hormone secretion. On the other hand, dopamine is important for sleep regulation and actually promotes sleep.
Good evidence for dopamine as being intermediary in the sleep-thyroid interaction comes from studies of restless leg syndrome, where there's actually a decrease in dopamine tone and an increase in kinetic activity, which has also been associated with states of excess thyroid hormone. It's a complex interrelationship, interacting at multiple levels. Both sleep and thyroid hormone function depend on each other.
Desai: Can you discuss how the different sleep stages are affected by the thyroid gland?
Shekhar: As many people may already know, sleep consists of two phases. One is called the non–rapid eye movement (NREM) stage of sleep and the other is the REM stage of sleep. Within NREM, there are three stages: stage 1, stage 2, and stage 3, also known as N1, N2, and N3.
N3 corresponds with the slowest waves of EEG activity, and it also is known as slow-wave sleep. It corresponds to the most restful sleep that we experience. Taken together, NREM and REM are anywhere between 70 and 90 minutes for one cycle, and multiple such cycles occur over the course of the night. It's important to understand that slow-wave sleep is the most important element of sleep that helps promote restfulness and energy.
As far as your question about specific stages of sleep is concerned, as I alluded to earlier, N3 is the most important stage of sleep from a resting standpoint. Unfortunately, regardless of thyroid hormone excess, which is seen in hyperthyroidism or thyroid hormone deficiency seen in hypothyroidism, N3 tends to be the most impacted.
There are other elements of sleep, such as sleep architecture, which includes total sleep duration, sleep latency, number of awakenings, and many other elements. The data are most clear about N3 being negatively impacted by hormonal imbalances.
Desai: Can you talk about how hypothyroidism and hyperthyroidism are different?
Shekhar: Hypothyroidism is a state of inadequate circulating thyroid hormone that occurs due to a number of different reasons, which I'm not going to go into too deeply. I'll give you an example. There was a study conducted on 30 hypothyroid patients where there was an increase in N1 and N2 and a decrease in N3 and REM sleep compared with controls. There was no change in sleep duration. Again, this was one of the initial studies that indicated a decrease in restful, or slow-wave or N3, sleep.
Similarly, a recently published analysis of the NHANES data, the national database here in the US, concluded that increased sleep duration was related to decreased free T3 levels. However, this association was significant only until subjects reached a threshold of 7 hours or more of total sleep duration. After reaching that 7 hours of sleep, this relationship was no longer significant.
In other studies, patients who have hypothyroidism have been shown to have an increase in the number of awakenings at nighttime, meaning they wake up or there are microarousals overnight and a reduction in slow-wave sleep occurs consistently. Mechanisms have been proposed, but a paucity of active thyroid hormones tends to be the most important element that is driving this.
Desai: That's a large amount of information for our listeners. I want to distill it. How do you differentiate between sleep problems caused by thyroid issues vs other sleep disorders? Should patients with sleep disorders get screened for thyroid problems? What would be the benefit of that?
Shekhar: Unfortunately, there is no great clinical way to do that. The best way would be to screen for thyroid function and thyroid dysfunction by blood tests. I think that it's important to also consider the specific circumstance of a patient who comes to you in the clinic. For instance, if you have someone in the clinic who's reporting daytime sleepiness, fatigue, cold intolerance, and weight gain, I think it's a no-brainer and you should go ahead and order a thyroid screening.
If somebody only has isolated sleep problems and they don't have other risk factors or other complaints that indicate thyroid dysfunction, it's probably important to consider other primary sleep problems. I still think it may be reasonable to screen for thyroid dysfunction on a case-by-case basis. The most important thing is to have a low index of suspicion for simple screening with blood tests in these patients.
Desai: If you find somebody with hypothyroid or hyperthyroid, how long does it take for sleep patterns to improve after starting either levothyroxine or treatment for hyperthyroidism with methimazole, radioactive iodine, or surgery? What is the expected time for improvement?
Shekhar: There are not many data published in terms of the timeline for recovery of sleep and treatment of these conditions. I will cite maybe one study, which was able to demonstrate subjective improvement in quality of life a few weeks after initiation of levothyroxine in patients who had hypothyroidism.
More than setting community standards, I would probably suggest to most patients that improvement in symptoms, especially if you have hypothyroidism, can take weeks — and in some cases, even months — and sleep dysfunction will also improve along that same timeline.
Now, if after a few weeks of treatment, they are not experiencing relief and they're snoring, they have sleep apnea, or they have other conditions, in those circumstances I think the first task of the endocrinologist is to assess whether the treatment is even working. It may be possible that they may be underreplaced, they are not absorbing, or they are not taking the medication.
If you've ensured that those elements are not at play, then I think it's quite reasonable to recommend that these patients undergo a specialized sleep assessment because there may be some other primary sleep disorder underlying their thyroid dysfunction. I think it has to be monitored over time, but after a few weeks, there should be some response in most patients.
Desai: Can thyroid hormones themselves, like levothyroxine, cause any sleep disturbances? My patients often ask me, "Is there an optimal time of day to take my thyroid medication to minimize any sort of sleep disruption?"
Shekhar: Unfortunately, again, this is an area that has not been as deeply studied as we would like it to be. I will point you to one study, published out of the Netherlands by Bolk and colleagues in 2010. It compared thyroid function tests and clinical outcomes such as lipid values and quality-of-life measures, which included fatigue scores, in patients who were taking levothyroxine at bedtime vs levothyroxine first thing in the morning. In both conditions, patients were supposed to take it on an empty stomach, meaning there was some gap between their previous meal and intake of levothyroxine.
The authors found that there was no difference in quality-of-life measures between those who were taking these medications at bedtime vs in the morning. While sleep was not directly addressed in the study, I think there is adequate reason to believe that sleep measures would also be equally treated whether the patient takes it in the morning or at bedtime. The key is to take it on an empty stomach, especially in the case of levothyroxine, and follow the other instructions that come with it. Timing of day doesn't tend to be a major factor.
As far as anti-thyroid medications are concerned, they are usually taken two to three times a day initially. Most prescribers will end up prescribing once a day when it comes to maintenance dosing. There's not any report on them being directly responsible for any sleep disturbances, which is good news.
Desai: In summary, it doesn't really make a huge impact, what time of day you're taking your thyroid hormone, as long as you're taking it on an empty stomach and waiting an appropriate amount of time to take food and medications.
I want to switch topics a little bit. We talked about hypothyroidism and hyperthyroidism, but conversely, I want to talk about how sleeping, the amount of sleep, and the quality of sleep you get can impact your thyroid gland.
Shekhar: That's an important question. I think we touched on it very briefly earlier. What has been shown is that sleep disruption tends to alter thyroid physiology. Some studies that come to mind are studies of sleep disruption and performing frequent thyroid hormone assessments. Multiple studies, most of them published in the 1990s and early 2000s, have shown that those who have sleep disruption or restricted sleep have, in many cases, increased levels of circulating thyroid hormones.
That tends to be an adaptive mechanism because their neurons require more energy, and more mitochondria need to fire. There tends to be that increased thyroid hormone secretion, and by contrast, there tends to be a decrease in TSH amplitudes at bedtime. In other words, one could extrapolate and say that sleep restriction tends to be associated with subclinical forms of hypothyroidism as an adaptive mechanism.
Desai: I think you've briefly covered that if you're getting less than 7 hours of sleep, your T3 levels decrease, with one particular study showing that.
Shekhar: That was based on data from NHANES. From a very clinical standpoint and practical terms, ensuring healthy amounts of sleep, making sure it's good sleep hygiene, and some of the other measures that tend to be associated with good sleep can go a long way in restoring thyroid physiology.
Desai: Can you quickly review those, like 8 hours of sleep, and what are some of the other recommendations that you have to help patients improve their sleep?
Shekhar: Absolutely. I think the most important element, which unfortunately is not adequately emphasized, is sleep hygiene. The general recommendation is that most adults require anywhere between 7 and 9 hours of sleep, and it has to be uninterrupted for them to be at their optimal capacity.
Some lifestyle measures can assist with adequate sleep. I'll start with room temperature. Most patients will set a temperature between 65 °F and 70 °F. It may be somewhat different in patients who have thyroid dysfunction because there may be cold or heat intolerance. You have to individualize that temperature based on their clinical status.
Another measure is going to bed at the same time every day and waking up regardless of it being a weekday or a weekend, and avoiding the use of electronic devices, especially close to bedtime. I'm sure not many people are following that.
There's also the issue of the mattress being comfortable, making sure that the environment of the room is cool and dark, and that noise levels are kept to a minimum. Doing daily exercise can help, especially about 4-6 hours prior to bedtime; it is recommended that patients engage in some activity. It's important to not eat heavy meals right before bedtime. If people are hungry, they can have a light snack. Avoiding caffeine and alcohol right before bedtime is also important.
These are simple measures but they can go a long way in ensuring that patients get adequate sleep.
Desai: Important sleep habits to improve thyroid health. You talked about how thyroid disorders are more common in women, but are there different aspects if you have special populations, such as children, older adults, or pregnant women?
Shekhar: Sometimes they will just manifest with GI symptoms, having a high heart rate, or some nonspecific symptoms, but they'll also complain of sleep problems. I think many of these patients do get missed. I'm pretty sure we are missing some of these patients because they have nonspecific symptoms. It’s important to keep a low threshold for assessing thyroid function.
There is a distinct element called apathetic hypothyroidism in older patients, where they have one isolated issue. Again, keeping a low threshold when they are complaining of something is important.
Unfortunately there's also a rise with age in sleep disturbance. If there is an underlying thyroid problem and there is an aging individual, there tends to be a double hit on their sleep cycle, which can sometimes worsen outcomes. There has to be some special attention here.
As far as pregnant women are concerned, again, sleep tends to be affected by a range of issues, independent of thyroid function. Things like having to wake up in the middle of the night multiple times to go to the bathroom; having aches and pains; having gastroesophageal reflux disease; and having back pain — all those things can really impact their ability to have restorative sleep.
In addition, as your audience may know already, there is a high burden of thyroid dysfunction during pregnancy. Hypothyroidism tends to be worsened because of increased demand. The other extreme is hyperthyroidism, where an entity like hyperemesis gravidarum can lead to nausea but also can lead to hyperthyroidism and impact sleep. In fact, one study found that almost two thirds of patients who had hyperemesis gravidarum had sleep disruption. That tends to worsen along with hyperthyroidism.
Finally, there is also some association between restless leg syndrome, which can occur in pregnancy, and thyroid dysfunction. Again, it's complicated to put it in one sentence. I think screening these special populations is very important.
A last sentence, about children: They tend to have similar symptoms like adults, but sleep is also important for their growth. If sleep is not adequate, especially during important parts of pubertal development, their growth can be negatively impacted. It's important to keep in mind those finer details when dealing with these patients.
Desai: There isn't much research done on this topic. Is there emerging research or treatment options that may be coming out? Or do you just recommend those lifestyle changes?
Shekhar: First and foremost is to individualize treatment, and I think that's as far as clinical care is concerned. As far as research is concerned, I think it's quite fair to say that it has been lagging. There have not been many high-quality studies performed with these individuals addressing these subjects, which is due to a range of issues.
As far as the prospects of further research are concerned, I think the potential is immense. The reason I say that is because people are getting used to wearing smartwatches, trackable devices, and sleep monitors, which tended not to be the case 10 or 20 years ago. Many of them are relying on those activity and sleep monitors to dictate how they live their lives. That also presents an opportunity to assess sleep in real-world settings.
There are plenty of data out there to suggest that actigraphic sleep monitoring, which is using a Fitbit-like device, is very highly correlated with polysomnography, or the traditional sleep study. Using those data, plus the capacity to study so many individuals across geographical boundaries, really allows us to delve deeper into the subject. Unfortunately, we have not yet realized that. I think we are just at the tip of the iceberg at this point, but the potential is immense.
Desai: Thank you so much. What advice do you have for our listeners? What are the top three things to take away from this podcast?
Shekhar: What I would like most people to understand is that sleep and thyroid function are very tightly related. There are many overlapping and interacting fields. By helping one aspect, you can really help the other aspect.
It's also very important that we set expectations for our patients and we counsel them appropriately. For example, when we are starting somebody on treatment, we can advise that they also implement sleep hygiene measures and keep a low threshold for referring patients for things like obstructive sleep apnea assessment, which tend to be very common.
Finally, if there is some suspicion of an underlying primary sleep disorder, as endocrinologists, it is our obligation to refer them to a sleep specialist who can adequately assess those issues and treat them.
As long as we detect it, screen for it, and refer these patients out and counsel our patients, I think we will be doing the best we can.
Desai: Thank you. It was an honor to have you join us today to talk about sleep and thyroid. Please stay tuned for upcoming episodes of the Thyroid Stimulating Podcast.
Cite this: Sleep and Thyroid Function: Addressing One Improves Both - Medscape - Jul 18, 2024.
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