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.
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.