Adrenal insufficiency: a general information post (does not replace medical advice)

[Lysistrata]

Hi all - I just wrote an absolute essay in response to a question about adrenal insufficiency (AI from now on in this post) from steroids. Since this is a question that may crop up periodically (I know I've answered it before), I thought I would copy it here for general information, and to link to in other posts if anyone wants to know about tests, what AI is, how it's treated etc. This may start to be more common if asthmatics who were previously steroid dependent are able to taper down their steroids after responding well to biologics. Or for weirdos like me who don't respond to pred but took too long to realise... Obviously be aware I'm not a doctor and this isn't medical advice - it's my experience plus some basic knowledge you can find online.

This website, plus two others I have linked to below, may be helpful. Please note that it talks about Addison's Disease which as I explain below is actually just one type of AI, but it does include information about secondary AI and about adrenal crisis: addisonsdisease.org.uk/addi...

This is really long, apologies in advance, but I hope it’s useful! I have added extra information about basic cortisol blood tests as well as the short synacthen tests that Mark-F asked about (please note you can also have a full day test to measure cortisol levels more closely but it seems uncommon for secondary AI from steroids and I have no personal experience, so haven't included that here).

I have adrenal insufficiency from long term pred (in my case 15 months and 1 year long courses with lots of short courses in between). I have very weird asthma and I don't really respond to oral steroids, so my specialist clinic managed to get me off pred which I'm very grateful for - sadly the weirdness also means I'm not eligible for any mAbs! However, coming off pred also revealed that my adrenals weren't happy so now I have AI.

Usually with AI that results from steroid use it's technically not Addison's disease, though you may hear that used as a general term for AI. Addison's is usually used to refer to a type of primary AI; with Addison's your adrenals don't work to produce cortisol and some other hormones that regulate salts. With AI from steroids it's generally a type of secondary AI, and usually the issue is just with cortisol production and not other hormones. The pituitary gland usually tells your adrenals to produce cortisol with a hormone called ACTH, but with secondary AI from steroids, the pred basically told your pituitary gland that you already had cortisol, so it didn't bother to keep stimulating the adrenals with ACTH to produce any more. When you stop the pred, your pituitary might not pick up the idea that it needs to produce ACTH again, and therefore the adrenals won't bother to produce cortisol. Sometimes the pituitary can start working again and sending ACTH (so you can sometimes recover from secondary AI if it's steroid-induced, which you cannot from Addison's), but sometimes the adrenals just stop bothering and won't produce what they need even when stimulated with ACTH.

This link may help: hopkinsmedicine.org/health/...

EDIT: It is possible to get AI from inhaled steroids only, but it is fairly uncommon and would usually happen with higher doses. This isn't a reason not to take your inhaled steroids: AI can be managed, dying from asthma because you were worried about the risk of AI cannot (to put it bluntly) - so don't run the high risk of a serious asthma attack to avoid the much lower risk of AI. (This actually applies to all kinds of steroids: if you need them for asthma, you need them).

It's also possible to get AI from multiple repeated short courses of oral steroids. Everyone is different, and some people can tolerate high doses without much effect, others will have a lot of side effects and get AI on lower steroid doses.

You might get an initial cortisol test with your GP/clinic: this will not be massively helpful if you are still on higher levels of steroids and/or it's done randomly. You need to have got down to about 5mg and be able to stop steroids for a short time, usually 24 hours, for this to be useful, and it needs to be done at 8-9am so they can compare reference ranges: time of day is very important for cortisol! If this is very low it shows you have a problem. If it's normal, and was done properly (ie right time, off steroids for long enough) then you probably don't have AI. If it's in between, they should do a short synacthen test to get more information about your adrenals and pituitary.

The short synacthen test is basically looking to see what happens to your cortisol levels when they’re stimulated with ACTH, so they ask you to stop steroids for at least 24 hours beforehand (that includes any nasal sprays and also your steroid inhaler as well as pred.) I would definitely talk to your asthma team if there are any problems with stopping. My original instructions said try to stop steroid inhaler for 48 hours; I did 36 and had an admission shortly after which my endocrine nurse specialist felt might be related to missing 3 doses of Fostair, so she said not to stop for more than 24 hours - this is fine for the test. EDIT: I've now been asked to stop my Avamys nasal spray for *72* hours before the test; the others are the same so far.

The test should be scheduled to start at 9am and you might feel a bit grim from stopping the steroids, so if you're travelling to have it it may be worth staying nearby the night before – though not the end of the world if you can’t. Also a good idea to take something to do as you just sit there in the test for an hour plus.

A nurse will check your vital signs, put in a cannula, ask what steroid-containing meds you take and when you last had them. A doctor should then come and talk to you to explain the test and get your consent. The nurse will then take your blood at 9am (or as close to it as possible – cortisol levels vary throughout the day and are highest in the morning, and they use 8am or 9am reference ranges). Then you’ll get an injection of synacthen (artificial ACTH) and they will take blood half an hour later, then half an hour after that. Once that’s done the test is over and you can take all your drugs again – yay! So make sure to bring them to the test. I am the person who makes noises and ends up needing Ventolin every time I have this test (3 times now), because apparently lungs need those inhaled steroids even if I don’t do much with pred.

They’re looking to see what your baseline cortisol and ACTH levels are and what they are at 30 mins and 60 mins. If you can get above a certain level of cortisol then most likely everything is fine. If you don’t, it means your adrenals aren’t producing the cortisol they should and you need to replace it. In my case my baseline cortisol in all three tests has been above the ‘concerning’ level but below the ‘ok’ level, but then doesn’t rise to the level it should at 30 and 60 minutes despite the ACTH (and my own ACTH levels are fine too), so I have secondary AI - which I may still recover from and they are retesting to see.

If you do turn out to have AI, you should be referred to an endocrine specialist – I see a fantastic nurse specialist who I wish I could clone as an asthma nurse lol. Most drs/nurses who are not in endocrinology appear to be deeply scared of the entire area and will do all sorts of odd things, so it’s worth educating yourself as you will probably need to guide non-endos if you are admitted to hospital. (My endo nurse clearly knows this and has provided me with various numbers for the endo dept ‘in case you have any trouble). Your asthma team should know the basics but they should not be trying to manage AI without endocrinology input, so push them if they don’t refer you.

For treatment: you can take pred but it’s more usual to take 20mg of hydrocortisone in divided doses (20mg hydrocortisone =5mg pred; hydro is less strong than pred and lasts less time, but is closer to your natural cortisol). That dose may vary but 20mg is the usual starting dose. The highest dose is in the morning as that’s when your natural cortisol production is highest and you need to try to replicate that - dose timing is important. I was prescribed it twice a day but do 10mg about 6am (I wake up earlier than I need to, take it then go to sleep again), 5mg at about 11.30am with my Phyllocontin and 5mg at 4pm. This was after I joined a Facebook group (Adrenal Diseases Self Help Group – lots of useful info if you’re on FB). I did start with one dose of 5mg pred in the morning but I was feeling absolutely dead by the evening on that, so the switch to hydro split doses really helped. Also as it’s a low dose and replacing your natural cortisol, you are unlikely to get the side effects as with high pred doses.

They tried seeing if I could reduce my dose to get my adrenals working again but it didn’t last so I’m back up to 20mg total in the three doses.EDIT: made it down to 10mg baseline total daily dose again in 2021 EDIT: made it all the way off hydro with restored adrenal function in June 2021. It helped not having lots of pred courses, but I didn't need to adjust my asthma meds. If I'd needed pred for asthma I would have taken it (though how much it helps is another question).

You will also need to updose (usually double each dose, so for me it was 20mg 6am, 10 mg 11.30am, 10mg 4pm) if you are ill or seriously injured, because illness is physiologically stressful for the body, and that uses cortisol you're not producing. There is guidance on this but you may find you need to tweak it eg it says you don’t need to for colds, but I find I often need to because colds trigger my asthma.) In general my asthma absolutely gobbles cortisol so I will updose if it’s flaring even if not hospital level. You’ll also need it for some procedures (including major dentistry, surgery, and things like colonoscopy – never had any of those so far thankfully but I know I’d need to updose). Fevers also tend to mess with cortisol. You do not usually need to updose for 'normal' emotional stress like exams (unless that really sets off asthma), but may need to for something like a bereavement or a major shock.

The one time I have had an adrenal crisis so far was a virus setting off asthma – I tripled what was my baseline dose then and it wasn’t enough. (Should it be relevant, official advice for COVID if you have AI is to quadruple the baseline dose). My endocrine nurse has commented that there is a bit of a lack of information for people who have steroid-induced AI in terms of how it works for illness, taking steroids for the asthma etc so be aware of that.

You should definitely ask whoever you see for advice on updosing and how to recognise low cortisol and crisis in yourself, though that may also be individual. For me low cortisol - which isn't the same as crisis but might become one if I don't get on top of it - is feeling very very sluggish, hard to wake up, very slow brain, bit dizzy. When I had a crisis I also threw up twice and thought I had norovirus, but since the injection sorted me out it clearly was the crisis itself (though vomiting from other causes has specific guidance - ask about this as you may need to take special steps if you have eg a stomach bug with AI, such as visiting urgent care when others wouldn't need to).

You will also need to ask for an emergency hydrocortisone injection and be shown how to use it (I was convinced I would not be able to, but I did it despite the fact that adrenal crisis can make you into an absolute idiot in my limited experience. I took far too long to work out I should use it - but I did it and I have no experience of injecting myself.) Always take the kit with you on trips, and ideally have two so you can keep one with you at work, one at home etc.

EDIT: Hilary39 has also reminded me that keeping a strip of hydrocortisone tablets on you at all times is also a good idea. Even in hospital steroid treatment can be delayed/withheld, or you might be out and have forgotten you need a dose.

Please also see below for Hilary's reply if you are pregnant and have AI.

Finally, you will need to get some kind of medical alert bracelet/tag that says you are steroid dependent and have AI - that doesn't have to be an expensive official one, I have a bangle from Amazon which does the job where I told them what to engrave. The Pituitary Foundation also has useful resources and advice: pituitary.org.uk/informatio...

I’ll stop now as this is already a huge essay - if you got all the way to the end well done and I hope it was helpful! 😊 Please feel free to add any comments from your own experience of AI, or ask questions if I wasn't clear.

[Hidden]

I have AI too, my adrenals are functioning at about 5% cortisol production. This is a very useful summary, thank you Lysistrata. I've found the ignorance around this problem amongst the medical profession absolutely astonishing.

[hilary39 in reply to Hidden]

Me too! I was sent away from the emergency room during my adrenal crisis in spite of the fact I was shaking and vomiting everywhere (like literally all over the hospital bathroom). The doctor on call wanted me to wait until the morning to get a cortisol test and THEN take HC when the common protocol in any medical school book is to do an IV of 100 mg of HC asap along with saline.

Thank goodness I figured out what was going on from doctor google and a kind pharmacist reopened her pharmacy and filled the HC prescription they gave me at the hospital. I immediately took 100 mg and started to recover but I'm still traumatized if you can't tell Their ignorance could have killed me, literally!

And no doctor ever warned me AI was a possiblitiy in spite of the fact that they prescribed me prednisone constantly. The ignorance really is a big issue in the medical community.

[Lysistrata Administrator Community Ambassador in reply to hilary39]

Ugh that's terrible! What a dangerous and scary experience The Pituitary Foundation has some useful materials for that kind of situation (see link in my post).

I thankfully haven't had to deal with that level of ignorance myself, but they wanted to reduce my hydrocortisone to 10mg on the ward once, 2 days after I had a crisis and when I still had acute asthma and the virus that had triggered it. It was just ignorance and they fixed it when i insisted, but a good job I knew it was a stupid idea and was able to insist.They seem to really struggle with the concept of updosing for illness sometimes.

They also like to forget/debate for absolutely hours about what I should be having, causing me to miss doses - I learned not to give up all my steroids to them so I could have a sneaky dose if they're being ridiculous. Also got told once while on 40mg pred that as I'd had an extra dose yesterday at 1pm I should skip my dose today and start again tomorrow. errr no. If pred worked for my asthma that would be a bit of a gap and it was definitely too big a gap for my adrenals.

[Lysistrata Administrator Community Ambassador in reply to Hidden]

Glad it was helpful - and yes it is quite scary the way endocrinology is kind of a black hole. And then they still think they know better than me and mess with the hydro dose! I'm always impressed when they actually listen and get it right (for me the danger point is when they realise I don't need pred, but then don't register that I need more hydro if I don't have pred. It seems to confuse them so much).

I find that there is often a LOT of confusion over steroids for asthma vs for adrenals and it's hard to get across - to doctors and in groups. I explain I don't take pred for asthma and why, but that I need hydro for adrenals and get 'so why do you take hydrocortisone instead of pred for asthma then?' or 'You do know you need steroids for asthma too'? ' AGHHHH I JUST EXPLAINED!

[Tugun]

Thank you so much for the information. I had no idea that illness etc uses more cortisol but it makes sense when you think about it.

[Lysistrata Administrator Community Ambassador in reply to Tugun]

I have to explain this sometimes (yes asthma counts!) and am always pleased when they get it.

[Angelgoth]

thank you for posting this, lots of really good and helpful information.

[Lysistrata Administrator Community Ambassador in reply to Angelgoth]

Thanks! Glad it's helpful.

[ninelives]

Bless you for such a detailed and informed post.

Have been on prednisolone for 17 years and told won't be able to come off it.

But your post will be really helpful for other folk on prednisolone and what the procedures are.

[Lysistrata Administrator Community Ambassador in reply to ninelives]

Thanks! You probably already know this and may well have one, but just in case - you should have a medical alert as well for steroid dependence. (I say this because it was never mentioned when I was actually on high dose steroids, when I still would have needed medical staff to know about it if I couldn't tell them myself).

[ninelives in reply to Lysistrata]

Thanks for thinking to remind me -yes have a meditag bracelet.

After a respiratory arrest a lovely hospital doctor said that since I was not breathing and no meditag they were working in the dark.!

[hilary39]

Lysistrata this post is SO GREAT and I really wish I'd had it to read a year and I half ago when I was diagnosed with secondary AI after having an adrenal crisis. Our experience / lessons learned are identical. This is a great resource to refer people to in the future who ask questions about AI--how lovely you took the time to type it up <3

The only thing I can think to add is that you also often need to updose during pregnancy during the third trimester (a common change is 20 mg to 25 mg) and then during birth, you need 100 mg of HC via IV every 6-8 hours.

Thanks again for doing this! This community is so supportive.

[Lysistrata Administrator Community Ambassador in reply to hilary39]

Thanks for adding that Hilary - I knew nothing about the requirements during pregnancy/birth as I haven't been in that situation, but it makes sense as it seems like pregnancy and birth is hard work and physiologically stressful in some aspects (I know it puts a strain on the heart for example). I hope it all goes smoothly for you!

I started typing and then didn't stop lol - but it really is, as you and others have found, an area where we need to be well educated because there's a scary lack of knowledge out there. I could probably write a book on '101 inventive ways to prescribe hydro wrongly' as there's apparently many ways to do that...

[watergazer]

An informative post thank you x

[Mogget]

This is really interesting and informative; thank you for taking the time to share. Is it something that is expected to improve? I.e. Will your adrenals start working normally again?

Do you know whether it’s something which can affect people who take multiple short courses of pred (but do not take it daily)? I often feel dizzy, foggy, tired and sluggish but don’t whether that’s down to my thyroid problems or asthma or something else.

[Lysistrata Administrator Community Ambassador in reply to Mogget]

Hi Mogget - with steroid-induced AI it is possible to recover and people do, which isn't generally possible with other types such as Addison's.

I know they were hoping mine might and they are doing synacthen tests yearly to keep an eye on things, but all 3 tests have been quite similar despite managing to lower my hydro dose by half for a while. However I was starting to struggle on that and needing to increase it a lot due to dodgy lungs/asthma flares so last time the endo nurse advised me to just have 20mg as a baseline dose; she did say she's starting to think mine may not really recover but they will keep monitoring. I am still on high dose inhaled steroids plus a nasal spray and also sometimes do get pred courses if it's not my usual hospital (it's unusual not to give them for asthma flares and many places are scared not to given it's in the guidelines).

It's definitely possible to develop AI from frequent short courses of pred, or even just from inhaled steroids, though that's unusual and shouldn't stop anyone who needs them from taking them, especially since using ICS to control asthma usually means less pred which has a higher risk for AI. They generally advise that you need to start being especially aware after about 2-3 weeks on pred above about 20-25mg, but frequent short courses can do it. I actually came off my long courses ok but then found I needed to taper off short courses which they usually say isn't necessary - well it isn't if you have them rarely but I did need to by then. I stupidly listened to someone who didn't get that (or really anything about my asthma), didn't taper and boom AI appeared - I think it was just waiting for the nudge, so I then stayed on 5mg pred till I could be tested.

If you're getting all those symptoms it's definitely worth looking into and thinking about how you come off those short courses, if you have a lot of them ie consider not just stopping even though that's the standard advice for isolated short courses. I also have a thyroid condition (well ok actually I don't have a thyroid at all lol) which is actually ok to manage but I know there can be some interaction with that and adrenals.

Perhaps talk to GP initially and see if they could do a cortisol test (but see above about timing for this)? And perhaps get thyroid checked if you haven't recently as well. As mentioned I do find asthma tends to use up cortisol, so if you have any problems with AI and are also struggling with asthma they're likely to be making you feel worse. If the asthma is bothering you a lot then also worth checking in with GP there too of course - not sure of your situation but it sounds like you're not very well controlled if you need a lot of pred courses.

Hope this helps!

[Mogget in reply to Lysistrata]

Thank you for the comprehensive and informative reply! Fingers crossed that your adrenals do eventually recover.

I had a fair few pred courses throughout 2018 and 2019 as my asthma control declined a lot during those years. I started Xolair in Feb this year and have only had one pred course since then. But perhaps my adrenals have been messed about by those earlier courses.

Interesting that you have hypothyroidism too. I’m on levo and my blood results are within range but I still feel unwell (as do many other patients). Adrenals could be a factor but it’s not really a recognised thing in conventional medicine and there isn’t a whole lot of research dedicated to thyroid disorders and the wider bodily holistic piece. So I think I will indeed speak to GP but I’ll just stick to the asthma/pred side of things when discussing potential adrenal issues.

Thanks so much for your advice!

[Hidden]

Excellent post 🤩

Could I just add that it isn’t only on very high doses of inhaled steroids and isn’t as rare as doctors often think: FLUTICASONE is likely to cause varying levels of suppression even on medium doses. Other ICS are lower risk eg Alvesco.

Also, they have now identified a genetic risk too: homozygous rs511198 genotype with a preserved FEV1

Apparently using the spray with the spacer is much higher risk than using the powder version.

Source: thelancet.com/journals/lanr...

I’m researching this because I have complete HPA axis suppression ie undetectable ACTH and critically low cortisol, due to Seretide 500 Fluticasone a day. This is a MEDIUM level dose, albeit top of the medium range according to NICE.

Dreadful gap in doctor knowledge 😰

[Hidden in reply to Hidden]

Edited to add source

[Lysistrata Administrator Community Ambassador]

Not addressed to you Koala as you weren't suggesting this, but just a reminder to anyone reading this that you should not try stopping your ICS because you're worried about developing AI. Doctors may not always be aware that ICS alone can cause AI and they shouldn't dismiss it, but equally, plenty of people take ICS long-term and don't get AI.

Also, AI is not ideal and can be dangerous, but it can be managed. Asthma is also not ideal, can be dangerous, but can be managed in the majority of people - with ICS plus/minus other meds. The risks need to be balanced, so it isn't something to try yourself.

I'm sure most people wouldn't consider doing this, but I've seen some posts on this forum with concerns about ICS, so I really want to make this clear that uncontrolled asthma is a significant risk in itself.

[Hidden in reply to Lysistrata]

Reducing ICS needs to be done under consultant guidance and very gradually -

source: my doctors

I’m now on 175 a day down from 500 a day Fluticasone but this has taken over 3 months so far and Montelukast was added. Plus Biologics soon. GP and respiratory consultant and endocrinologist all know.

I agree with Lysistrata that ICS can’t be stopped without tapering. That could be fatal if there’s adrenal suppression involved (often undiscovered)

[Lysistrata Administrator Community Ambassador in reply to Hidden]

Agree re consultant guidance for reducing ICS. But also, as I've mentioned elsewhere, stopping ICS at all is not currently recommended for any asthmatic - you appear to be extremely unusual if your doctors are recommending no ICS at all. I'd imagine it's an approach not all doctors would agree on either - you might well find a different team wouldn't even try to address AI this way.

Guidelines are not laws, and they differ in terms of whether they approve of people at the 'mild' end being on ICS alone. However, they do agree that almost all asthmatics should be on some kind of ICS. GINA (Global Initiative for Asthma) no longer recommends reliever-only treatment for anyone at all, and recommends ICS for everyone to reduce risk of exacerbations and symptoms - there is a paper I came across at work which suggested that ICS seems to be helpful even in patients with mild asthma who don't have raised eosinophils.

That recommendation may change in future for some patients (eg trialling a non-ICS for certain patients). However, we're not there yet, and stopping ICS at all for patients with asthma, even with medical supervision, is generally not recommended. Again, I recognise you have that medical supervision but I want to emphasise to others that this is unusual.

Others who have problems with fluticasone and/or the spray (MDI) formulation could perhaps ask about trying a different ICS.

[Hidden in reply to Lysistrata]

I don’t have a letter yet but jn the appointment she said the team thought Montelukast + Biologics going forward without steroids.

Let’s see what the letter says I’ll let you know.

Endocrinologist just called. We agreed no hydrocortisone but have it ready. He’s testing cortisol and ACTH after Easter 👍

[Hidden in reply to Hidden]

I’m massively allergic with a mountain of allergies so maybe that’s why? They’re treating it as an allergy disorder first?

[Hidden]

I’m going to test my cortisol soon. Ordered a test from Forth. So far they’ve matched the hospital lab results so I think they’re reliable.