Sleep problems are common in people with pituitary disorders
Dr Claire Ellender (Sleep Fellow) and Dr David Cunnington (Sleep Physician) from Melbourne Sleep Disorders Centre discuss common sleep problems seen in pituitary disorders.
- 00:00 – 05:20 Brain mechanisms that regulate sleep
- 05:20 – 11:10 Common sleep problems in pituitary disorders
- 11:10 – 15:25 Sleep apnea
- 15:25 – 16:40 Cushings disease and sleep
- 16:40 – 21:58 Sleep apnea treatment
- 21:58 – 23:35 Circadian rhythms
- 23:35 – 24:48 Pituitary hormones and their effect on sleep
- 24:48 – 25:56 Summary
Dr Claire Ellender is the current Sleep Fellow at Melbourne Sleep Disorders Centre. She has recently completed Respiratory Physician training, working at the Princess Alexandra Hospital in Brisbane and The Alfred Hospital in Melbourne. She has a wide range of interests, including respiratory and sleep physiology, pulmonary hypertension, medical education and insomnia. Claire has published in the areas of pulmonary hypertension, chronic dyspnoea and interstitial lung disease.
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David Cunnington: Hi. I’m David Cunnington and I’m here with Dr. Claire Ellender who’s a sleep fellow who’s working together with me at Melbourne Sleep Disorders Centre and we’re going to talk to you a bit about how the pituitary interacts with sleep and some of the things we think about when we’re seeing people with pituitary problems who have got problems with their sleep.
Claire Ellender: So we’re having a look at how the pituitary gland interacts with sleep. Certainly if we’re having a look at the anatomy of it, there are lots of associations of the pituitary gland with structures that control sleep.
Before we sort of go into all of the anatomy side of things, it’s really interesting to try and make a definition of what sleep is. It’s different things to different people. If you think about it yourself, sleep is when you’ve got quietening of the body, quietening of the mind, not aware of what’s going on around you and when we see it in another person, we see them being quite still, lying down often, not a lot of movement in their body.
There’s restorative functions to sleep, helping to reset some of the chemicals in the brain and in the body as well. Then when we’re looking at sleep studies in the sleep lab, there are specific findings that we look for in the brain activities and the muscle activities to actually define sleep.
So it’s a pretty tricky thing to actually put in a sentence and say exactly what it is. So it’s not surprising when I show you this picture of a brain here, that there are lots of different structures that are involved.
So there’s the filter that sort of filters out a lot of the information coming in from your senses, your hearing as well as your body position and that’s one of the roles of the thalamus and sort of an important filter.
In terms of being – that feeling of wakefulness versus sleepiness, the hypothalamus is very important with that. It’s the site where there’s a build-up of hormones and different proteins and chemicals in the body during the day and that sort of helps. The combination of all of these and the balance of them influences the feeling of sleepiness versus wakefulness during the day. The cerebrum or the cortex as it’s also known is where a lot of our thinking and our fine motor skills go on.
So they’re all in similar areas around the body and there’s a very important structure that we will talk a little bit more about in a few minutes called the pineal gland and that’s a gland that makes a very important hormone called “melatonin” and that’s one of the master switches between day and night and the body clock that sort of governs lots of other areas of the body including things like control of blood pressure, influences insulin sensitivity, and also influences the release of other hormones like cortisol hormone.
The sort of minute by minute control of sleep is by something called the “homeostatic sleep drive” and that is mainly controlled in the hypothalamus which is very near the pituitary gland. You can see here on this picture.
These structures here, they’re controlling sleep through the night and there are stages of sleep that we go through. This picture here shows us sort of over time, down here on the bottom axis, the different stages of sleep.
Stage one and two, sleep tends to be your lighter sleep and stage three, sleep tends to be the deeper sleep where a lot of hormonal releases is regulated such as growth hormone and most people in a normal situation would go through every 90 minutes of the cycle from the lighter sleep down to the stage three sleep and then have periods of dreaming sleep or REM sleep which is when the muscles are paralysed. So there are cycles that we all go through during a normal night’s sleep.
So, normal sleep is a balance between the hormones and the pathways that make us feel sleepy and the balance of turning those on and turning off the wakefulness pathways and sort of a balance between the two in the normal situation.
Overriding those sort of shorter term mechanisms I spoke about before, there’s something called the “circadian rhythm” which is that master body clock, the 24-hour clock, and the circadian rhythm gets triggered off by the release of a hormone from that pineal gland we saw earlier and that controls the balance between sleep and weight but it also controls a number of other pathways such as the release of hormones like cortisol, our temperature, clocks as well, things involving metabolism, like insulin sensitivity and diabetes, and also blood pressure control. So it’s a really important major – a major sort of switch in pathway.
In terms of the types of sleep disorders we see, one of the most common ones you might have heard about fall into the category of sleep-related breathing disorders and lots of us have heard of OSA or obstructive sleep apnoea. You might know a friend who’s on a CPAP machine. I will show you some pictures about that a little bit later.
There are also some disorders where – the signal down from the brain to tell us to breathe at night time can go a little awry and that’s something called “central sleep apnoea” and there are complex interactions in people when they carry a bit much weight as well and we know that it’s obesity hypoventilation syndrome.
Insomnia is something a lot of us have heard about and suffered over our lifetimes and that’s a category in its own, right? There are different types of insomnia. So that’s certainly an important type of sleep disorder.
Those body clocks I mentioned earlier can go a little out of whack as well. So there’s a whole category of different disorders with the circadian rhythm, that body clock rhythm. We classify them as circadian rhythm disorders.
Some people have problems with controlling the boundaries between wake and sleep and are really sleepy during the day. That’s disorders of hypersomnia and then I’m sure we would have met someone around the traps who has had some sleep walking or sleep talking. They fall under a category called parasomnia.
Finally, the category of sleep disorders called “movement disorders,” things like the restless leg syndrome that you might know someone who has – these are the major categories that we see of different types of sleep disorders.
So the common pituitary disorders that also have associated sleep disorders fall under sort of two main categories. So you can have difficulties where there’s too much hormone production and then there’s another category where the pituitary gland gets enlarged and it causes a physical – we call that a mass effect squashing other structures.
So with the functioning problems where there’s too much hormone production, there are three main hormones that can cause problems with sleep. One of the most common ones is acromegaly and that’s a disorder where the pituitary is making too much of growth hormone or the precursor hormone that tells the body to make growth hormone and that can lead to the obstructive sleep apnoea and we will talk a little bit more about how that happens.
You can also get central sleep apnoea as well, Cushing’s disease, which is too much cortisol or ACTH, the precursor that can also cause obstructive sleep apnoea and problems with thyroid secreting tumours and structures can lead to difficulties with maintaining or initiating sleep and that’s characterised by insomnia.
Then certainly there are conditions where the mass effect can squash the pineal gland and that’s that gland involved in the body clock rhythm and causing circadian rhythm problems.
Sleep actually can also have an impact back on both the hypothalamus and the pituitary and that access the interaction between the two.
For example in people with sleep apnoea, they have trouble with their sex hormone secretions and also if you’re not getting enough of that deeper sleep, the slow way of sleep, it can influence the amount of growth hormone that your body makes. So there are interactions both ways.
I’ve mentioned obstructive sleep apnoea a couple of times but it would probably be good for me to explain a little bit about what that is. So obstructive sleep apnoea is a problem where when people are off to sleep at night, they get relaxation of the muscles in their upper airway and the tongue is one of those big muscles that is in and around the airway and relaxation, sleep comes on, leads to the muscles relaxing and narrowing down, the tongue flopping back and causing there to be less air being able to get down into the lungs and that’s the obstruction part, like the tongue flopping back in the air pipe narrowing down.
Not enough oxygen getting down into the lungs leads to there being not enough oxygen getting to the brain at night time and there are lots of signals and lots of receptors that the brain has of course to be able to register that and when that’s noticed by the brain, a big alert system gets sent off. A big surge of activity in the brain is sending some activity to those muscles to tone back in those muscles and that leads to then people getting activity in their brain when they should be asleep, so they’re not getting a nice, restorative quality night’s sleep. So that’s sort of the principles of sleep apnoea.
David Cunnington: Some of the common things I see people present with or the symptoms people get either with sleep apnoea or other sleep problems with pituitary problems is feeling more tired during the day than they would expect, even though they’re getting adequate amounts of sleep or feeling that they’re sleeping pleasantly well.
Sometimes it can be trouble getting to sleep, trouble staying asleep or not sleeping at the right time. So that’s often a sign of the circadian rhythm problems where people can’t get to sleep at the time they want to get to sleep or can’t wake up at the time they want to wake up.
Less commonly with pituitary problems, what we do see is movement disorders during sleep where people get involuntary movements either of the legs or other limbs and sometimes it will just be an observer saying that this person is restless, moving around a lot and the person who has got the problem might actually be unaware of it.
Claire Ellender: Acromegaly is really quite commonly associated with obstructive sleep apnoea. So depending on what study you look at, some of the original studies, they found about 20 percent of people having sleep apnoea but in the more modern studies, there’s more like two-thirds of people or more having obstructive sleep apnoea, so certainly a common association.
Why is that? Well, sleep apnoea in acromegaly is common because there’s often an enlargement of the mandible. There are often slightly different shaped jaws and that means that often there’s crowding of the back of the throat. The tissues tend to be enlarged because of the influence of growth hormone on soft tissues like muscles and fat and that squashes your airway and your windpipe as well.
The strength in those areas tends to be a bit weaker. So you’re more likely when you take a big breath in, to have collapse down of the air pipe and that can lead to air not being able to get in, which is one of the main problems in obstructive sleep apnoea.
The tongue can certainly get very big. You often see in people with acromegaly, lots of teeth marks on the side of their tongues. It’s sort of a really key giveaway sign that we look for.
Big enlarged thyroid glands or something called a “multi-nodular goitre” can be seen. That sort of also can put some pressure on the windpipe and carrying too much weight in anyone is a bit of a risk factor for sleep apnoea, but particularly in people with acromegaly-associated sleep apnoea.
So if you’re having a look at the back of the mouth, we’ve got the big tongue contributing to sleep apnoea, crowding from those increased tissues. So it’s no wonder that there’s a really strong association between those two conditions.
Acromegaly also can lead to that central sleep apnoea I mentioned. Central sleep apnoea is that under-breathing problem where the message doesn’t get down from the brain well and in acromegaly, the levels of growth hormone and the precursor can sort of lead to cyclical under-breathing, so the message is not getting down properly and then the message is not getting back up properly, so problems with the feedback mechanisms.
So you kind of got a two-pronged difficulty in getting the signal down to breathe properly and that can lead to people having really poor quality of sleep, either from the signal not getting through properly and then oxygen levels falling and the brain getting really stimulated as sort of a panic response through the night from that low oxygen level.
Also from the sort of forces on the body overnight from that under-breathing leads to the brain not getting that restorative deep quality sleep that makes people feel refreshed.
Interestingly, the different types of sleep apnoea tend to respond differently when the problem in the pituitary is treated. So the central sleep apnoeas, that under-breathing from the signal problem, that does tend to improve as by chemical control of the hormones is achieved whereas interestingly, the obstructive type with the problem of the mechanics and the blocking from the big tissues and problems with the structures, that doesn’t always improve despite getting good control of hormone levels.
So one of the predictors is really if your tongue volume gets smaller over time, that’s more likely to help and if your jaw structure changes improves that – those two things are most strongly associated with obstructive type of sleep apnoea getting better controlled.
So it’s one of the reasons why we always follow people up after they’ve had treatment for their pituitary disorders, to make sure if they’ve got a response and if not, then make sure they’re on the right therapy.
Cushing’s disease is also associated with obstructive sleep apnoea. Through the mechanisms I mentioned earlier but also obesity is a really important risk factor in the relationship between Cushing’s disease and sleep apnoea. Some of those other mechanical structures are not quite so much of an issue.
This is something that we really like to make sure we screen for and provide good quality treatment advice for our patients because both sleep apnoea and Cushing’s disease increases the risk of cardiovascular disease in patients.
So the combination of the two can lead to serious increase in the risk of cardiovascular disease, so things like heart attacks and strokes.
We also can see insomnia in our patients who have Cushing’s disease from that high level of cortisol and we think that two of the mechanisms might be – first of all, there’s less slow way of sleep so that deeper sleep and also less sleep efficiency of the amount of time that you’re spending in bed. The amount of time you’re actually asleep is less. So people can complain of insomnia.
So we’ve talked a lot about obstructive sleep apnoea. Why is it so important? I’ve alluded to that a little bit with relation to the cardiovascular risk. So we know that people who have severe obstructive sleep apnoea and moderately severe obstructive sleep apnoea certainly have all cause mortality, so an increased risk of dying for any reason much greater than people who have lower obstructive sleep apnoea scores.
This busy table is just showing you that from a number of different studies all around the world, when we look at really important problems like stroke, heart disease, high blood pressure, problems with insulin and diabetes, problems with abnormal heart rhythm, arrhythmias, there’s certainly an increased risk compared to people who don’t have sleep apnoea with these conditions.
So it’s certainly something that we want to make sure we pick up. So we can try and help prevent some of these risks.
CPAP therapy is often one of the things that we recommend for patients who have got obstructive sleep apnoea. So there are two photos here, his and her CPAP machines. You can see that there’s a box that sits by the bedside and then a long tube that goes to a mask that goes on people’s faces.
Now these two people both have masks that go over their whole faces but there are many, many different types of masks and one of the things we do spend a lot of time on is making sure that people get the right mask for their face shape and I’ve mentioned face shape is a big contributor to sleep apnoea and a lot of conditions.
So there are many different types and basically the way these machines work is blowing air in to try and hold open that windpipe so that the oxygen can get down and then these people can get a better night’s sleep.
We’ve got evidence again from a number of trials showing that using CPAP in people who’ve got sleep apnoea, have improvement in their sleepiness scores, improvement in their blood pressure scores, improved insulin resistance, so less likelihood of diabetes and some smaller trials showing some improvement in risk of stroke.
So certainly we have evidence to show that if we treat severe sleep apnoea, we improve people’s profiles with those risks I just mentioned.
David, I’ve just talked about CPAP a little bit, the mask and machine. But are there some other options that patients can use if they’ve got sleep apnoea?
David Cunnington: There are a lot of options in terms of treating sleep apnoea and what options we use just depends on how bad the sleep apnoea is. So if sleep apnoea is severe, really then CPAP is the option that we use.
But if sleep apnoea is relatively mild or moderate, the other options are things like a dental appliance so that’s called a mandibular advancement splint. A device that fits in the top and bottom teeth and the aim is to bring the lower jaw forward, which in turn brings the tongue away from the back of the airway and opens up the airway.
Another option is looking at surgery. So, surgery can be used to reduce the soft tissues in the upper airway, so things like taking out the tonsils, removing the adenoids. We do tend to do that much more in young people than older people because it seems to make a difference particularly in kids and adolescents but less of a difference in adults.
There’s some other surgery on the palate or reducing the size of the tongue. That can be used. Another treatment is a thing called Provent, some nasal valves. So they’re adhesive valves that sit on the nostrils that increase the pressure in the back of the airway and that connect – in some respect, it’s a bit like CPAP but rather than having to be connected to a machine, the little valves sit on the nose. They can be a bit fiddly and don’t work for everybody but that’s another option we will sometimes use.
Then really for people, if it’s trouble just when they’re sleeping on their back will keep them off their back, so use a positional device, so that people are just sleeping on their side rather than on their back. Of course there are the general meters about making sure weight isn’t an issue and ensuring that your nose is nice and open and people aren’t getting a blocked nose.
Claire Ellender: In patients who have got pituitary disorders and sleep apnoea or any sleep problems in particular, there are some specific things that you sort of see a little bit more commonly causing troubles with getting established on therapies.
David Cunnington: It can be nasal congestion. So that can be an issue particularly in people with pituitary problems. Sometimes if the pituitary problems are related to craniofacial abnormalities, it causes the nose to be narrow at the back or other times, it can be just nasal congestion that we need to deal with like a non-allergic rhinitis that we need to deal with.
Also in people with pituitary problems, some of the problems we get is a partial response to treatment. So if the main response people are after is I want to feel less tired during the day, often the sleep problem is only part of it. There are other aspects of the pituitary condition that’s going to make them a bit more tired. So yes, we manage the sleep apnoea or we manage the insomnia but it’s not expecting that’s going to be all of the problem and necessarily fix all the people’s tiredness symptoms.
Claire Ellender: So there’s often more than one thing going on. So I talked a bit about the circadian rhythm before. That’s the master body clock and sunlight is really crucial in triggering off these symptoms. So in the back of our eyes, we have some receptors that then trigger off signals down to the pineal gland, that master hormone-secreting gland I mentioned and that secretes a hormone called “melatonin”. That has influences in the hypothalamus to override those switches of day and night with the 24-hour day/night cycle.
Also influences the release of other hormones like cortisol and influences things like body temperature. So it’s a very important master switch in the whole body.
We sometimes see people who have some mass effects with big pituitary glands, squashing that little pineal gland, have troubles with their body clocks. So here’s an example of what we call a sleep diary. So this is where our patient – for different days of the week has noted down and shaded in boxes when they’re asleep.
A normal one would usually pretty much go to bed around the same time and pretty much wake up after a similar amount of time.
But this person here has had – you can see over time them getting – their bed time getting later and later and that’s because that body clock isn’t sending off that master signal switch at the same time. This person has got a problem with their body clock.
So changing tact a little bit, what about sleep disorders and how they influence the pituitary? Well, we know that many people who have got severe obstructive sleep apnoea have reduced libido and people have looked into why that might be and found that some of the sex hormones such as testosterone and one of the precursors, the luteinizing hormone in men, is certainly a lot lower if they’ve got uncontrolled severe obstructive sleep apnoea, even when you control for things like being overweight and other precursors that are – can influence testosterone.
The good news is if we can get people appropriate therapy, for example the CPAP, the mask and machine, those levels of testosterone have been shown to improve over time. So certainly there are influences both ways.
So in summary, there’s certainly lots of links between pituitary disorders and sleep disorders. Sleep disorders are common especially in people who have got pituitary disorders. They are a little bit more complicated. There’s often an increased impact because there are other reasons for having difficulties such as tiredness and there’s certainly common links with cardiovascular risks and disease.
So it’s really important for people who have got pituitary disorders to be screened for sleep disorders particularly obstructive sleep apnoea in people who have got acromegaly and Cushing’s disease.
So we always like to help GPs and endocrinologists and anyone involved in the care of people who have got pituitary disorders to keep sleep disorders, particularly sleep apnoea in mind.
Well, I hope that was helpful information for everyone, a bit about the combination of problems that pituitary disorders and sleep problems can lead to.
David Cunnington: Thanks for all the work you put into that Claire. I think that has been a really helpful explanation for people and if people are looking for more information, there are the resources at the Australian Pituitary Foundation or also resources about sleep on the SleepHub website.
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