Adrenal Insufficiency

We unfortunately had to educate ourselves recently on the issues surrounding cortisol replacement since my partner is in the same boat – in his case ipi/nivo caused hypopituitarism, so this is technically secondary adrenal insufficiency, but this is immaterial.

How do the doctors know how much cortisol you need? The answer is, they don’t . Yes it is to an extent weight dependent, but it also more importantly depends on other factors, and most importantly it changes depending on your stress levels, your current health condition, whether you exercised recently etc etc. There is no good way to reproduce the way your body controls your cortisol levels. What is true though is that cortisol levels that are too high cause morbidity and excess mortality, mainly from cardiovascular disease. Doctors used to think that 30mg hydrocortisone is the correct physiological replacement dose for most people, but in the last 20 or so years they realised that lower doses, like 20-25mg is actually better for most people. This is equivalent to 5mg prednisone. So this is why sing123 your doctor is advising you to take this dose provided you have no side effects on it. But it is unlikely you will be able to go down under less than 15 mg  unless your body starts producing some cortisol again, which can be tested easily, and I am sure your doctor will schedule tests from time to time (an easy test is just morning cortisol). I am sure she also told you that you can take more hydrocortisone if you feel stressed and that you need to take more if you are sick (sick day rules).

In general the problem with cortisol replacement is that it is hard to replicate the natural cycle of cortisol production. Cortisol concentration raises at night while you are asleep, is highest in the morning and goes down during the day, then is low in the evening. Taking replacement of 15mg in the morning causes your cortisol to peak higher than natural levels and then quickly dip, taking 5mg causes another peak and another dip. There is no solution to this problem currently. I attach a link to an article that explains all this (I suggest you get a full version access)

https://www.sciencedirect.com/science/article/abs/pii/S1521690X08001085?via%3Dihub

Lucas, prednisone is longer acting than hydrocortisone, hence you only need one dose in the morning. It is also a cheaper drug. I think hydrocortisone has other advantages over prednisone though in terms of long term side effects as far as I know, which is why most people on long term replacement would be on hydrocortisone. So you might want to read on it, or ask your doctor to try and switch to hydrocortisone if he feels that it is appropriate.

As far as I am aware there is just one slow release drug in existence, called Plenadren. It is approved in the UK, don’t know about the US. It is relatively inexpensive (around 300 pounds per month). It doesn’t emulate the night time rise in cortisol though. You could try it if your endocrinologist agrees and see if it is better? For my partner it is still early days but perhaps he will try it later on. Right now he just splits hydrocortisone into smaller and more frequent doses.

We will be trying to find good endocrinologist with experience in hypopituitarism. Hypopituitarism caused by imunnotheraphy is no different from hypopituitarism caused by other things – in the end you just have hormonal deficits and the question is how to replace and manage them best.

The damage as far as cortisol production is concerned is nearly always permanent, sadly. So the replacement is for life.