Adrenal fatigue does not exist: a systematic review.

[RogerBlack]

https://www.ncbi.nlm.nih.gov/pubmed/27557747

BACKGROUND:
The term "adrenal fatigue" ("AF") has been used by some doctors, healthcare providers, and the general media to describe an alleged condition caused by chronic exposure to stressful situations. Despite this, "AF" has not been recognized by any Endocrinology society, who claim there is no hard evidence for the existence. The aim of this systematic review is to verify whether there is substantiation for "AF".

METHODS:
A systematic search was performed at PUBMED, MEDLINE (Ebsco) and Cochrane databases, from the beginning of the data until April 22nd, 2016. Searched key words were: "adrenal" + "fatigue", "adrenal" + "burnout", "adrenal" + "exhaustion", "hypoadrenia", "burnout" + "cortisol", "fatigue" + "cortisol", "clinical" + "burnout", "cortisol" + "vitalility", "adrenal" + "vitality", and "cortisol" + "exhaustion". Eligibility criteria were: (1) articles written in English, (2) cortisol profile and fatigue or energy status as the primary outcome, (3) performed tests for evaluating the adrenal axis, (4) absence of influence of corticosteroid therapy, and (5) absence of confounding diseases. Type of questionnaire to distinct fatigued subjects, population studied, tests performed of selected studies were analyzed.

RESULTS:
From 3,470 articles found, 58 studies fulfilled the criteria: 33 were carried in healthy individuals, and 25 in symptomatic patients. The most assessed exams were "Direct Awakening Cortisol" (n = 29), "Cortisol Awakening Response" (n = 27) and "Salivary Cortisol Rhythm" (n = 26).

DISCUSSION:
We found an almost systematic finding of conflicting results derived from most of the studies methods utilized, regardless of the validation and the quality of performed tests. Some limitations of the review include: (1) heterogeneity of the study design; (2) the descriptive nature of most studies; (3) the poor quality assessment of fatigue; (4) the use of an unsubstantiated methodology in terms of cortisol assessment (not endorsed by endocrinologists); (5) false premises leading to an incorrect sequence of research direction; and, (6) inappropriate/invalid conclusions regarding causality and association between different information.

CONCLUSION:
This systematic review proves that there is no substantiation that "adrenal fatigue" is an actual medical condition. Therefore, adrenal fatigue is still a myth.

Seems relevant given that some claim this is the cause of 'burnout' - which is often conflated with CFS.

 

[boolybooly]

Interesting.

At the risk of courting controversy, I have never been particularly convinced by the concept of adrenal depletion in my own case because the biochemical precursors are too common and its easy for the body to make steroids if the tissues of the adrenal gland are intact. Where the pituitary is involved this can be seen as a regulatory issue rather than simply pituitary pathology.

In ME with immune symptoms I think its possible steroid production might conceivably be downregulated over time consistent with the biological priority for immune activation to fight an immune threat like viral activity.

This is because steroids tend to prepare for activity and suppress the immune system. Where an immune threat response is under way the biochemical logic is to reduce steroid production and minimise stress inducing physical activity which takes energy away from the immune system.

This would be consistent with the way unavoidable stress and therapies which compel activity can be so harmful for PWME.

When a previously active person stops making as much steroid, you would expect them to experience stressful phenomena in a different way, as Dr Paul Cheney characterised it, they will be less able to cope with complexity due to steroid reduction.

This does not mean that stress causes ME, its more the other way round, when ME strikes the impact of stress is greater.

This might also have a bearing on the apparent gender bias in ME, though that may be complicated by other issues and may deserve more study to get an accurate picture of reality.

 

[keenly]

Adrenal glands can literally shrink due to b5 deficiency.

 

[Mary]

@RogerBlack - I don't think this proves that adrenal fatigue does not exist. It seems to be saying that the studies which were analyzed were poorly designed for various reasons and so do not provide "proof" of adrenal fatigue. But it does not therefore follow that adrenal fatigue is a myth. Poorly designed studies do not prove anything.

Just look at how the medical profession treats ME/CFS - there is no definitive biomarker (well, some may argue this point) and therefore, it's all in our heads.

Just because proper testing or studies are lacking, does not mean that something does not exist.

I've had severe fatigue which appeared to be related to my adrenals. It followed periods of severe stress, and the fatigue was alleviated by adrenal glandular products.

 

[TigerLilea]

I've had severe fatigue which appeared to be related to my adrenals. It followed periods of severe stress, and the fatigue was alleviated by adrenal glandular products.

Could it be that the severe stress caused the fatigue and once the stress was relieved that your fatigue went away? Having known people that have had adrenal issues and how sick they were before diagnosis, I find it suspect that an MD wouldn't be able to find "adrenal fatigue" if it existed.

 

[Philipp]

I think what's important to keep in mind that when using the term 'adrenal fatigue', people in medical science usually mean very literally adrenals 'fatiguing' (whatever this may actually mean). That does not mean there is no HPTA axis dysfunction, cells losing their sensitivity to whatever hormone is implicated, disturbed circadian rhythms or whatever else may be affected by or have an effect on cortisol etc etc - usually it literally just means 'the adrenal tissue itself works as it should when stimulated'. And if, like here, conflicting methodologies and contrary findings are what one gets out of a review then this suggests that better research is needed more so than that anything is proven/disproven.
Apart from that, for pretty much the reasons I just mentioned ye olde 'AF' is a bit of a stupid term to describe anything. We don't call hypothyroidism 'thyroid gland fatigue' either. Same problem as ME has, in my mind - or are we sure yet that all cases of what we call ME today are actually a -myelitis type illness?

What annoys me personally about the discussion surrounding this topic is the logical leap from 'there is no evidence that whatever symptoms you are describing are adequately explained by a very vague term with no agreed upon definition' to 'therefore, you do not have the symptoms you described and are completely fine so get out of my office', or 'this cortisol test gave us a result of you having an abnormal daily rhythm, but does not tell us why you have that' to 'therefore, there is nothing wrong with you and it is not possible for you to feel tired'.
I have witnessed stuff like this a couple of times with young MDs of whom I thought (up until that point) that they generally knew what they were talking about and how logic works.

 

[ljimbo423]

My view of adrenal fatigue is that the gland itself is working okay. I think it's the HPA axis that is probably dysfunctional and causes the adrenal gland to become dysfunctional. It seems like HPA axis dysfunction might also cause many other symptoms.

These organs and their interactions constitute the HPA axis, a major neuroendocrine system[1] that controls reactions to stress and regulates many body processes, including digestion, the immune system, mood and emotions, sexuality, and energy storage and expenditure.

LINK

Jim

 

[Esther12]

I've got not idea about the details, but have noticed that those offering treatments for 'adrenal fatigue' often seem to be those who are a bit quacky in others ways too. I give the whole thing a wide berth.

 

[Mary]

Could it be that the severe stress caused the fatigue and once the stress was relieved that your fatigue went away? Having known people that have had adrenal issues and how sick they were before diagnosis, I find it suspect that an MD wouldn't be able to find "adrenal fatigue" if it existed.

No. I first took Drenatrophin PMG (adrenal glandular by Standard Process) in the 1990's - I felt weak as a kitten and didn't have a clue as to why. I had had severe lifelong stress, the origins of which were (I think) from childhood abuse. So I was constantly stressed - the stress never went away. And within a few days of starting Drenatrophin, my energy started to return.

Then a few years later my house flooded. I thought I was handling it fine but about 3 or 4 days after I was hit with bone deep fatigue, and realized my adrenals had taken another hit, and I restarted the Drenatrophin and energy returned again.

Now maybe as some are saying it's HPA axis dysfunction instead of the adrenals in particular - maybe. All I know is my adrenals seem to be my Achilles heel. I avoid stress as much as possible but it's not always possible to avoid and generally my energy starts to tank when under stress, and up my glandular and feel better.

Also I was getting chronic sore throats and then learned that they could be a symptom of pantothenic acid deficiency and pantothenic acid of course is crucial for adrenal health, so I started taking that and it helped as well.

You know how good doctors are with issues like these - one gave me Prozac - yes with no tests or anything just gave me Prozac. I hated the way it made me feel and stopped it after 2 days. We all know that if you go to the doctor complaining of being tired or weak, they want to give you an antidepressant. Maybe they'll look for anemia first, but that's about it.

eta: I'll revise my answer a little: yes, apparently the fatigue was due to severe stress and I think the mechanism of stress causing the fatigue was the adrenals being overloaded or weak by the stress.

 

[bspg]

Just because proper testing or studies are lacking, does not mean that something does not exist.

Absence of evidence ≠ evidence of absence.

I feel like this concept is severely underappreciated.

 

[RogerBlack]

I do agree that lack of good research is not proof of absence, and had considered highlighting that.

But where absence is limited, selection of patients to treat, and what to do to be effective remains unclear, and any doctor who uses the term while claiming to treat, without making it clear precisely what they mean, and how they propose to treat, and verifying what their treatments have done is very, very likely to be inaccurate.

 

[boolybooly]

I completely agree this paper is rubbish. It was probably naive of me to focus on the subject rather than the paper itself in my post above.

The last line of the summary is a bit flip but could convey truth

Therefore, adrenal fatigue is still a myth.

were it not for the title which extends the conclusion well beyond the legitimate bounds of certainty.

Adrenal fatigue does not exist: a systematic review.

Showing that an idea has not been well researched is not the same as proving it does not exist.

If anything, it shows that an opportunity remains to undertake more definitive study.

So this appears to be a study with an agenda biasing the conclusions, potentially acting as propaganda for unknown agencies which might wish to persuade others that adrenal fatigue does not exist.

The kind of agencies which might have that kind of agenda could include medical insurers. So one has to raise an eyebrow and it suggests this kind of research should not be allowed to go unchallenged just because it is so bad and illogical.

 

[bspg]

So one has to raise an eyebrow and it suggests this kind of research should not be allowed to go unchallenged just because it is so bad and illogical.

Hmmm. This sounds strangely familiar...

 

[Philipp]

I don't think this review is done badly as far as I can see. They wanted to check if there is substantiating evidence for this AF condition, there apparently still isn't, the papers that exist are apparently pretty bad on average and that is what they reported.
I would have been surprised if they found anything else, since a paper showing actual problems with the adrenal tissue is something we of all people would have heard of by now.

 

[Mary]

So this appears to be a study with an agenda biasing the conclusions, potentially acting as propaganda for unknown agencies which might wish to persuade others that adrenal fatigue does not exist.

I get the same feeling from it.

I don't think this review is done badly as far as I can see. They wanted to check if there is substantiating evidence for this AF condition, there apparently still isn't, the papers that exist are apparently pretty bad on average and that is what they reported.
I would have been surprised if they found anything else, since a paper showing actual problems with the adrenal tissue is something we of all people would have heard of by now.

The problem isn't the paper per se, but its conclusions (and title). I'm not a scientist so would have no way of examining this paper (if I wanted to spend the energy on it), but I would be curious to see if someone who was knowledgeable about study design took a look at it to see if its conclusions were biased.

I am just reminded again of how the medical profession decided a priori that ME/CFS is all in our heads, so therefore scant research has been done and researched has actually been discouraged. You don't study a chimera.

With all the people taking things for their adrenals and HPA axis with this illness (hydrocortisone, licorice, other herbs, adrenal cortex extract, etc.), and abnormal cortisol levels seen in ME/CFS, you would think there would be some properly designed research carried out so that we would know what we were talking about - adrenal problems or HPA dysfunction etc. Unless it's been decided ahead of time that there's no point and we are all delusional.

 

[Philipp]

The title being an issue is actually a pretty good point, you're right - and the problems mirror those in CFS.
If you are aware that what they are talking about is literally just the minor point of the glands themselves having tissue damage instead of e.g. reduced signaling originating higher upstream, then it is fine (and also pretty inconsequential to patients).
If you are aware that the word 'fatigue' in CFS describes the same situation as in cancer fatigue, and the 'chronic' distinguishes one from the other mostly in terms of origin and length of time and you also know that this is not a vague term but has a clear set of definitions, it is fine.

But we know from experience that average doctors don't do that, much less people from outside the medical field. Like I said, my jaw dropped a bit when I witnessed the otherwise smart MD 'helping' someone by explaining that he 'likely just had htpa downregulation' without offering any actual help at all.

It mirrors the situation in research a bit as well, where we have decades worth of fighting about psychological treatments being worth +6% or -2% in functioning to the patients for ME/CFS which is not something any of us would care about if this debate wasn't tied to literally letting us live. No patient really cares about the academic debate of why his cortisol is too low in the morning unless it affects what can be done about it. Both fields, however, probably suffer a big deal from not really having a good idea at what to look at next or which technique would be best (for long stretches of time), so the low amount of meaningful research might actually be a bit of an artifact of that without any malignant intent behind it.
Of course, this only applies to the actual meaningful research, I am decidedly not talking about the sea of bullshit that was created to drown us out, but I hope this goes without saying at this point. Or at any point in the last couple of decades, really.

 

[bertiedog]

What I will never understand is when one has adrenal issues how traditional Endocrinologists will say that if on testing they find they just about respond to the ACTH test then everything is fine but that when you get to 99% loss of function and you are at the stage that any major stressor could kill you, then you have Addisons and it's an emergency and you need steroid replacement.

My point being they don't seem to accept that there is a stage when the adrenals are well under functioning which will drastically affect your quality of life and it can go on for many years. You can experience very low bp with things like severe disabling dizziness, blackness on bending down to tie up shoelaces or just to pick something up that you have dropped; you might find it impossible to get your blood sugar under control with it constantly dropping so low you get horrible symptoms of severe sweating, heart pounding, panic attacks, weakness and not to mention pain in one's muscles because of the inability of the thyroid to function properly because there isn't enough adrenal reserves. Naturally you won't be able to sleep well because your body is completely out of balance and it's a horrible place to be in but the traditional view is that you just have to wait and have no life until you reach the Addison's stage before you get any treatment.

Whether you want to call what I have described above as adrenal fatigue or not I know that it exists because I suffered with it for about 20 years before by chance I was lucky enough to find a private Endo who would treat me following a very thorough history and also because of the results of saliva cortisol/DHEA tests. I remember that taking hydrocortisone was the first drug that I could remember made me feel that I was glad I had taken it because up to then I always had horrible reactions to drugs and often couldn't tolerate them, in fact I would have reactions to so many things it was ridiculous.

Over time all that has stopped and though still sensitive to medications and needing low doses my body doesn't go into an overreaction the way it used to do and I don't have low bp anymore and no more blackness plus blood sugar is so much more stable. I got my life back and don't have hypo functioning adrenals anymore but only because I have to take a daily dose of steroid replacement but will never forget those years from 1979-2003 when I felt I had no control whatsoever over my body.


Pam

 

[Snow Leopard]

There certainly a lack of evidence that the adrenals play a role in ME...

 

[heapsreal]

I dont understand the drs that say adrenal fatigue/dysfunction seen in some cfsers and other condition with low dhea, morning cortisol in the lower third of the range when healthy people are in the upper third of the range, they refuse to acknowledge these results saying nothing can be found. Yet they will then turn around to that same person and say they have depression which itself has no biological diagnostic test and they diagnose purely of symptoms even in some cases when they dont have sad thoughts or feelings, which one would think would atleast be at the top of diagnosing depression??

 

[keenly]

There certainly a lack of evidence that the adrenals play a role in ME...

They play a role in everything.