Biologic Half-Life of Hydrocortisone.  Why is this important?

As Derek lives with Adrenal Insufficiency, we started looking into his steroid doses to work out whether he was on the best dosing schedule possible for him.

In 2016 we had an Endo appointment and asked for a Day Curve to confirm his dosing was right.  It was refused.  So we asked for 1 random cortisol blood test.  This was agreed to, more to keep us quiet than that the endocrinologist was actually looking for something.  What we didn’t tell him was what WE were looking for.

We both believed that his dosing at 3 times a day was leaving him with low cortisol in the middle of the day.  The only way to show this was to have a random cortisol taken right before his second dose of the day was due. His dosing at the time was:

6.00 am – 10mg / 12.00 noon – 7.5 mg / 4.00 pm – 5 mg

The problem with this dosing was that by 2.00 pm every day he was feeling like he wanted to sleep, and felt “blah”.  Some days he was also showing clear signs of low cortisol.

We had seen tables that said that cortisol had a Half Life of 8-12 hours, but that didn’t make sense.  We had also seen other tables that said 2 hours.  That was a big difference.  We needed to know what was going on for Derek.

1 Blood Test Tells It All

On the day we had set for the test Derek took his morning dose as usual at 6am.  We then did the things we normally do on a weekend, very little.   At 11.15 we went to the Lab for the blood draw.  We wanted it as close to his second scheduled dose of the day as possible.

When we got the results it showed what we already believed.  He was under range.  Not just under range for that time of day, but below range completely.  His cortisol was not lasting long enough in his body.  But we had been shown tables that said it had a biologic half-life of 8-12 hours, so how could he be below range in 5.5 hours?

This didn’t make sense even though we knew it was right.  So we started looking into what was meant by biologic half-life.  What we found out is very scary, very concerning, and actually very dangerous.

What did we find?

BIOLOGIC HALF-LIFE CAN BE RUBBISH.  It can be a false number, it shouldn’t be used in the way the below table indicates.

The table here is beening used by many groups/forums and on medical sites including on websites such as Endotxt.org, NCBI, and NADF so it must be right, surely.

Do NOT use this to work out the half life of your Hydrocortisone or Prednisone for dosing!

 

Here it was, the table we got shown constantly.  So Derek started looking further to try and find out where the biologic half-life came from.  The first thing he found was the definition for biological half-life:

 

“Time required by a body to process and eliminate half the amount of a substance introduced into it. Also called biological half-life, biological half time, metabolic half-life, or metabolic half time.”

A number of variations of this table appear on the Internet and use the column heading Duration of Action.  Other variations of this table simply classify the corticosteroids as short-, intermediate- or long-acting.  The same numbers apply no matter what the column is referred to as.

If this column truly is a (biologic) half-life, and we apply the rule of 5 half-lives for complete elimination, then that would mean that Hydrocortisone would be visible in the body for up to roughly 2 days (40 hrs).  Yet when Derek had a blood test before his morning dose, his cortisol was undetectable having had HC at 4pm the night before.  That was 17 hours and no detectable cortisol.  What would happen for the other 20+ hours?  It was clear there was something seriously wrong with this table.  None of this would be consistent with the title Duration of Action.

Also, if that was the case, you would only be prescribed cortisol once a day, not 3x, or more often now, 4x a day.

Where did this Table column come from?

There is no clear ownership of the table that we could find.  It is used, copied, and the copy is referenced, but tracking back to the original hasn’t been possible by us.  We do know it was created before 1980

He became very curious and decided to look further for the source of the information and came across this quote from “Principles of Endocrinology and Metabolism”,3rd edition, 2001, Chapter 78 “Corticosteroid Therapy” by Lloyd Axelrod.

This paper references the definition of:

“The commonly used glucocorticoids are classified as short-acting, intermediate-acting, and long-acting on the basis of the duration of the corticotropin (ACTH) suppression after a single dose, equivalent in anti-inflammatory activity to 50mg of prednisone.”

This is all about suppression of ACTH on high doses of prednisone, nothing to do with the amount of time you will remain within a safe cortisol range when you have Adrenal Insufficiency, yet Dr’s and patients alike use the table to justify twice a day dosing on HC.

So what are the implications of this table?

If someone uses this table to tell you that half-life is 8-12 hours for hydrocortisone they are wrong.

After looking for the original source of the table we discovered that the test was done as above, with a normal healthy person being given 50mg prednisone (approx 200mg HC).  The only thing that can be taken from the original research is that 50mg prednisone will suppress ACTH production for a period of time.  The hydrocortisone, and other drugs, were extrapolated from there (guess work based on poor knowledge).

If you had Primary Adrenal Insufficiency (Addison’s) and Hydrocortisone had a half-life of 8-12 hours, then taking HC every 6 hours would mean constant suppression of ACTH, and you would not have high ACTH after starting the steroid.  But we know this isn’t correct because many with Addison’s still have some part of their Addison’s “Tan” due to raised ACTH.  This is supported by the document below.

Professor Peter Hindmarsh is Professor of Peadiatric Endocrinology at University College London and Consultant in Peadiatric Endocrinology and Diabetes at University College London Hospitals and Great Ormond Street Hospital for Children. He is currently Divisional Clinical Director for Paediatrics at University College London Hospitals.  He also runs a website called CAHISUS.  He has written an article called GETTING CORTISOL REPLACEMENT OPTIMAL IN ADRENAL INSUFFICIENCY

The major goal of cortisol replacement in patients with adrenal insufficiency is to mimic as closely as possible, the normal pattern of cortisol production known as the circadian rhythm. The reason why we try to achieve this, is primarily to minimise side effects of over and under replacement and promote improved overall health. The two key factors are understanding the circadian profile and the pharmacology of hydrocortisone.

In this article Prof Hindmarsh talks about getting optimal dosing, and also looks at the absorption and clearance of people.  What he showed is that there is a very large variation between people. The article is well worth a read.  He also pointed out that the half life of hydrocortisone is a lot shorted than 8-12 hours, in fact, it is more like 70-90 minutes.

Another CAHISUS leaflet states this:

Hydrocortisone has a quick onset and the cortisol peaks to the highest level usually around 2 hours after being taken.  The cortisol obtained from the tablet lasts in the blood circulation between 4-6 hours.

This is a change from an old document by Prof Hindmarsh which included the old figures as above.  Things have changed, research has improved, and there is more knowledge out there.

What Does All This Mean in Steroid Dependant People?

For me?  Gobbledygook.  If you have a clear understanding of Half-Life, Clearance, and metabolism you may follow what is talked about in the studies.  Personally, it confuses the heck out of me.

I do however, understand the concept of half-life.  I first heard about it when watching a movie years ago about a child who had a certain amount of a chemical in his body at point C, and they claimed he had been given the chemical at point A.  It was pointed out that he would have drunk a gallon of the chemical to have the amount still in his system because of the half-life of the chemical.  The chemical had been very bitter and it would not be possible for the child to drink that much.  I became very interested in half-life.  I didn’t think then that it would be so important in Derek’s everyday life.

I had to ask Derek what everything he had found, and what the implications of half-life on hydrocortisone meant in layman’s terms, but even he struggled to explain it in a way that I could be easily understand. One thing he reminded me of is that while your Cortisol is going up, it is also being used.

I have also learned through this research is that even legitimate medical websites actually have misleading or wrong information.

When you are looking at a good way to dose for you, it must be an individual choice, based on how you feel between doses, whether you are willing to take multiple doses a day, and base it on signs and symptoms.  The fact that Derek felt low at the scheduled time of his second dose of the day, and this was supported by a blood test that showed low cortisol, meant we could get the Endo to agree that dosing more frequently was the right option for him.

Now that he is on a better regime of 4 times a day, he functions a little better, he has a low base level of HC, and in the last 6 months, has lost weight without trying, but not in a bad way.

I wish you all luck with this as I understand that there are many Dr’s out there who are not interested in listening to their patients on more dosing throughout the day.  One of the reasons for this is they don’t believe that you will be compliant, even though you are the one asking.

If they think you are asking for something that shouldn’t be done, then show them Prof Hindmarsh’s document above.

Advertisements

Worst-Case Scenario

What if I had an accident, not bad enough to require an ambulance, but that required me to go to Hospital?

Since Derek became ill I have had a “worst-case scenario” played over and over in my head.

For two years, I have imagined what would happen if I became incapacitated. For some reason, I couldn’t drive. What sort of impact would that have on the fact that I was the only driver in the house.

I have played it over in my mind many times, thinking “what would I do”, “how would I deal with the problems”. “What if I had to get Derek or Bevan to a medical appointment, or I had to do grocery shopping”.  “What are all the problems I would have to deal with?”

Who could I call.

My worst-case scenario? To break my right leg at home.

 Actual Event

Stepping down off the back lawn onto the steps. I felt my ankle roll to the outside. My mind immediately went to the thought of, “NO, This can’t happen”. So I tried to correct. But to do that I had to put my left foot down on the step. Great, I will be fine.

Imagine my shock when I realised too late that the step I was aiming for wasn’t there. I didn’t stop with both feet on the same level.

I stopped when I was layed out flat on the ground, having landed very heavily on my left knee. It hurt, but not as much as my right foot. That was screaming.

But over riding it all was the thought, “Crap, Derek is going to get a headache, need to go to bed, and I think I should probably go to A&E”.

I lay there for a few minutes, running everything through my mind, tears running down my face. I wasn’t sure if I was crying because of the pain, or because my worst-case scenario might be coming true.

While there, I worked out that I have hurt my left knee. I knew that because I could feel the blood, and I could feel the hole in my jeans. I still hadn’t risked moving my right foot. It was still yellowing for attention, and I was refusing to give it.

The reaslisation that I was the only one with a Drivers Licence, or that could Drive dawned on everyone. Offers of “I’ll call and ambulance”, “Do you want me to call an ambulance?” and other phrases including the word ambulance were used.

No, this was not bad enough for an ambulance. I felt sure I could get to my bed, rest it, and then see what was happening.

All this time I was pumping adrenaline like crazy.

This is a good example of how fast Derek reacts to an emergency. He walked over to me at his normal speed, and just stood there asking if I was ok. Not able to actually react in a normal way. I could tell that, because all he did apart from asking me if I was ok, was to call Bevan, who was already running to my aid from inside the house.

I finally managed to sit up and reassess the situation. My foot hurt, my mind jumped to “crap, broken it”, then moved slightly more slowly to “nah, it’s just going to be a bad sprain”. Ice, rest, and then a trip to A&E to get it strapped, and find some crutches for a couple of days.

I worked out how to stand up, with assistance. I then tried weight bearing. Great, I can stand on my foot.

1 step, 2 steps, that was it. No more. I was NOT able to stand on my own two feet.

Somehow, in that short time, Bevan had come up, assessed the situation, realised I needed help, and went and found my mother-in-law’s walking stick. Well done that son. I hadn’t even noticed he had left before he was back.

Bevan and our Boarder helped me inside (with me sliding down the stairs from the top of our back yard) to my bed, I was given ice.

As I lay there I realised that, even though I knew my eldest son who lived at the other end of town needed to go to bed at a reasonable hour, and that I was about to spend 5-6 hours in A&E, I sucked in my pride, accepted it as a fait accompli, I phoned him and told him the situation. He said he would turn off his dinner (which was almost cooked) and come get me.

No, I wasn’t having that, I wasn’t going to inconvenience him that much for a sprained ankle.

I took pain killers and lay there for an hour waiting for him. At first it was fine, I didn’t mind waiting as I knew it was just a sprain. I had time to go through each plan of how to get to work the next day as spraining my ankle wold mean not being able to drive for 24-48 hours.   I would need crutches but that was it.

By the time my eldest arrived to take me to hospital I was desperate. I couldn’t walk, I was in a lot of pain, even with pain meds,  and shock was setting in.

Derek on the other hand, was laying there, he looked worse than flat but not as bad as he has been some times. He took panadol, and just deal with the headache as best he could.

I worked my way to the car and got in the passenger seat. My instructions to my son was, on arrival at hospital, get me a wheelchair. I was NOT going to try and walk.

We checked in, we could see it would be a 4 hour wait at least. What was a girl to do. Post on facebook of course, where my daughter read about it.

At some point my daughter and her boyfriend (a paramedic in training) turned up. This was a great opportunity to send Derek home. He had taken extra meds, but still looked worse than me.

Finally I am taken out the back and seen, very quickly, by a Dr. Quick exam, “yes, think we might get an x-ray”.

1 found of x-rays and a 5 minute wait later and I get the good news. “Yes, you have sprained the outside of your right foot. But I need another x-ray of it. A slightly different one. That spot you say is the extremely painful, is where you broke it! But there may be another break as well”

Boom!

There it was!

Worst-case scenario now a Reality!

I am cast. Both figuratively and literally.

Oh, and I have to get Bevan to a Medical Appointment tomorrow a long way from home!

Boom! There it is again.

For the next two weeks I will probably be in a plaster case, at which time I have to see an Orthopaedics Specialist to see what they want to do. Even if taken out of the cast and put in a moon boot, I will not be able to drive for another couple of weeks.

Up to 4 weeks of not having a driver in the house.

Yup. My worst scenario is now playing out in real life.