Of Mice and Men: the importance of diurnal rhythm
It was five past six on one of those cold winter mornings when you need your slippers on before you shuffle onto the icy tiles of the kitchen floor. As I entered the kitchen, I had the impression of a leftward-moving blur below the rim of my specs. I blinked, rubbed my eyes and approached the hallway door, towards which the blur had been moving. Opening the door, I saw, for definite, a speedy mouse running along the skirting board and under the vacuum cleaner. My heart was racing, and I suddenly felt very much awake. I grabbed a Tupperware container and slowly lifted the vacuum with my left hand. Sure enough, there was the mouse and, slightly to my amazement, I was fast enough to catch it. Job done — and more excitement than I needed before I had even boiled the kettle.
So what has all this got to do with cortisol and diurnal rhythms?
In people with healthy adrenal glands, blood cortisol starts to rise at around 3am, and the daily cortisol concentration peaks between 6am and 8am.
This is one of the reasons we wake up and get out of bed in the morning.
Blood cortisol concentration gradually falls for the rest of the day, so levels are much lower in the afternoon.
By 10pm or 11pm, levels can be undetectable, even in healthy people. This is what makes you want to go to bed. That is why your endocrinologist will always recommend that your first hydrocortisone dose of the day is the biggest one, and that you should try to minimise doses after 3pm or 4pm.
Rodent adrenal glands are different in several respects from human and other primate adrenal glands. Firstly, they do not make cortisol; they make a similar hormone, corticosterone, instead. Also, they do not make sex steroids after birth, so the steroid DHEA that humans have is not found in adult mice. Importantly, nocturnal animals such as mice have a steroid rhythm that matches their activity: low during daylight hours when they are asleep, and high at night when they are active. This means that mouse corticosterone concentrations start to rise at 18:00 every day, and by 06:05 the next morning, the mouse I mentioned earlier had low steroid levels and was thinking about bed.
In contrast, at the same time, I was pumped full of cortisol and ready for a fight, even with a poor mouse. I am pretty sure that if we had had the same encounter at 19:00, the mouse would have been faster, I would have been slower, and it would have got away. However, because our diurnal steroid rhythms were in opposite phases, I had the advantage.
There is an emerging scientific field of research called chronobiology, which explores how biological processes differ at different times of the day. Cortisol and corticosterone rhythms are a central part of this research. You have probably already heard that food calories taken late at night are more fattening than exactly the same calories eaten first thing in the morning. There is also good evidence that you get a better response to a morning immunisation than you do if you have exactly the same vaccine in the afternoon. We are just starting to understand much more about how timing really matters.
This is also relevant to the advice we give steroid-dependent people who have to work late in the evening or do night shifts. If you are keeping the working hours of a mouse or an owl, then most likely you will feel better if you adjust your hydrocortisone dosing pattern accordingly. Moreover, if you want to catch a mouse, you have probably got a better chance first thing in the morning!
Professor Simon Pearce, Professor of Endocrinology, Newcastle
Managing Pain and Sleep Issues in Pituitary and Adrenal Conditions