Iron deficiency and dysregulation

D

DokaGirl

Senior Member (Voting Rights)
"Iron Deficiency Without Anemia – Common, Important, Neglected
Esa Soppi

Depatrment of Internal medicine, Eira Hospital, Laivurinkatu 29, FI-00150 Helsinki, Finland

DOI: 10.15761/CCRR.1000456


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Abstract
A serum ferritin concentration of <30 µg/L is the most sensitive and specific test for the identification of iron deficiency in patients with or without anemia. However, patients may be iron deficient at much higher concentrations of ferritin. Iron deficiency without anemia and with normal red blood count is a clinical challenge, and many patients have been diagnosed with a multitude of conditions ranging from hypothyroidism to depression to chronic fatigue syndrome over the years when they have sought help for their often debilitating symptoms. The key to a correct diagnosis are assessment of the serum ferritin concentration and a meticulous medical history focusing on the possibility of life-long blood losses and diseases such as celiac disease. Differential diagnostic causes for the symptoms must be sought for. The mainstay of therapy is oral iron in sufficient doses for at least 6 to 9 moths together with serum ferritin monitoring. Some patients who do not respond to oral iron treatment may need intravenous iron. The longer the iron deficiency has lasted, the more challenging the therapy may be. Some iron deficient patients without anemia may have had the condition for over a decade, and may not fully recover. The amount of human suffering, the loss of quality of life and the indirect costs to society caused by iron deficiency are huge.......

During my 30-year carrier as a consulting internist I have met hundreds of patients, mainly menstruating females, who have sought medical advice for prolonged (1–35 years) fatigue, brain fog, muscle and joint pains, weight gain, headache, dyspnea, palpitations (sometimes associated with sleep disturbances), arrhythmia, lump in the throat or difficulty in swallowing or restless legs. Over time, the patients have often received a spectrum of diagnoses and corresponding treatments: subclinical hypothyroidism, fibromyalgia, burnout, overtraining, asthma, somber mood extending from melancholy to severe therapy-resistant depression, chronic fatigue syndrome and chronic Lyme disease. It is important to include iron deficiency without anemia as a differential diagnostic possibility, because this type of iron deficiency is very often associated with symptoms that severely impair the patient’s performance and quality of life and may even hinder the patient from overcoming the ordinary challenges of everyday life and may cause permanent disability."
(my bolding)

https://www.oatext.com/iron-deficiency-without-anemia-common-important-neglected.php

This 2019 article is I think relevant to some with ME, who may also suffer from iron deficiency without anemia. As well as those with anemia. I believe that just as iron deficiency without anemia can masquerade as ME, so can ME mask iron deficiency without anemia. Several of the symptoms are similar, and this iron deficiency can go unsuspected by both patients and physicians. It's my understanding the go-to lab test for fatigue/anemic type symptoms does not include measuring the ferritin level. Something that the author of this article emphasizes as very important. Once missed, this iron deficiency is passed by, and other reasons may be sought for these symptoms, which may lead to further misdiagnoses.

Thank you for your comments.
 
Arnie Pye said:
I'm curious what you think of this paper?

Effect of iron supplementation on fatigue in nonanemic menstruating women with low ferritin: a randomized controlled trial
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In isolation not that much. As the authors say there is a problem with blinding because it is easy to tell you are taking iron. Rather like the PACE authors they conveniently avoided asking people if they could tell whether or not they were on treatment. More than half the improvement was seen with placebo so this was a trial set up in such a way that 'placebo effect' was a big issue - although it may well be bias from factors other than true placebo effect.

I think it is quite possible that some people with low iron without technical anaemia feel fatigued but the idea that it might mimic ME seems to me much less plausible. I am also pretty sure that a lot of physicians sell iron supplements to patients as a way of pretending they know what is wrong when they do not.

My own experience with people who were seriously iron deficient and anaemic with it is that fatigue was not an issue. In most cases I was seeing them for something else and iron deficiency came up on tests or they were pale.
 
A doctor finally tested my ferritin a few years into ME and my level was at 4. I took iron supplements regularly for years. My doctor didn't understand why my levels dropped so quickly and later realized that I had absorption issues, and undiagnosed h pylori.

I felt a different type of fatigue and dizziness from my ME symptoms when my levels dropped below 20. I was out of breath climbing just a few steps. I found that keeping levels above 50 made a difference.
 
Mij said:
A doctor finally tested my ferritin a few years into ME and my level was at 4. I took iron supplements regularly for years. My doctor didn't understand why my levels dropped so quickly and later realized that I had absorption issues, and undiagnosed h pylori.

I felt a different type of fatigue and dizziness from my ME symptoms when my levels dropped below 20. I was out of breath climbing just a few steps. I found that keeping levels above 50 made a difference.
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I am familiar with a result of 7 for ferritin. Testing the ferritin was done at the patient's request after the patient was advised they could not have low iron because their hemoglobin level was good. The two main symptoms for this person were fatigue and shortness of breath with exertion. This instance was decades ago, however it seems this same scenario still plays out today. When ferritin is not tested, despite symptoms that point to that as a possibility,
other avenues may be explored, delaying treatment for iron deficiency without anemia.

ETA: minor change for clarity (hopefully).
 
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Jonathan Edwards said:
but the idea that it might mimic ME seems to me much less plausible.
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@Jonathan Edwards in answer to your comment that it's doubtful that iron deficiency might mimic ME, the CDC cautions regarding other diagnoses causing symptoms similar to ME:

"Several conditions can cause symptoms that may resemble ME/CFS. If suggested by the history and physical examination, these conditions should be appropriately tested for, and treated if confirmed. Based on clinical presentation and history, these conditions could include:

  • Any active medical condition that may explain the presence of fatigue such as untreated hypothyroidism (including Hashimoto’s disease), hyperthyroidism, diabetes mellitus, iron deficiency anemia, other treatable anemia, iron overload syndrome, adrenal insufficiency, Cushing’s syndrome, anorexia nervosa, or iatrogenic conditions such as side effects or interactions of medication(s) or supplements." (my bolding)

https://www.cdc.gov/me-cfs/healthcare-providers/diagnosis/other-conditions.html

Physicians very well versed in ME would clearly see the differences between ME and iron deficiency.

Physicians not well versed in this complex disease may not, as per the ME Research UK article: https://www.meresearch.org.uk/research/other-resources/misdiagnosis-on-a-grand-scale/

From this ME Research UK article:

"... Yet, how valid a diagnosis of ME/CFS really is depends crucially on the rigour of the initial clinical assessment, and the efforts made to exclude other treatable conditions that might be causing the collection of symptoms. If the examination is cursory – and if the clinician is sceptical, alienated or just plain disinterested – the “diagnosis” can easily become a convenient lay-by for clinically complex cases that don’t fit into any other category.

Every year ME Research UK gets about 400 calls or e-mails from patients.... patients reporting that they have improved after being re-diagnosed with and treated for another condition. These conditions have included Addison’s disease, multiple sclerosis, sleep apnoea, primary mitochondrial disease, primary liver disease and paranoid schizophrenia – and in every case the caller has been content with the re-diagnosis and/or the new treatments it has brought....

In the first – originally published in 2010 in the Journal of the Royal College of Physicians Edinburgh (1) – researchers examined the records of every patient referred by local GPs to the Newcastle CFS/ME Clinical Service. The key finding was that 103 (40%) of referrals were eventually diagnosed with other conditions which could explain the concatenation of symptoms. The main alternative diagnoses in these patients were fatigue associated with a chronic disease (47% of all alternative diagnoses); a primary sleep disorder (20%); psychological/psychiatric illnesses (15%, most commonly, depression, anxiety and post-traumatic stress disorder); and cardiovascular disorders (4%).

The second, recently published report examined the prevalence of alternative diagnoses in patients referred by GPs to the specialist clinic at St Bartholomew’s Hospital, London (2). Its major finding was that a diagnosis of “CFS” was eventually confirmed in only 54% of patients. Of the rest, 53 patients (21%) were given alternative medical diagnoses (most commonly primary sleep disorders, endocrine disorders, nutritional disorders and pain disorders), while 54 patients (22%) received alternative psychiatric diagnoses (most commonly a depressive illness or anxiety disorder)." (my bolding)


Although this article doesn't mention iron deficiency specifically, it does note "nutritional disorders", as one of the misdiagnoses.
It is shocking, but not surprising the range of misdiagnoses noted in this article.

I think sound knowledge of ME, which we know has been seriously lacking for decades, lack of rigour in clinical assessments, health policy restraints, protocols etc., could add up to someone being diagnosed as having ME, when they are iron deficient. This could be the case as ferritin does not appear to be included in the first round of testing patients may receive. If more in-depth testing is not done, iron deficiency could be missed.
 
DokaGirl said:
I think sound knowledge of ME, which we know has been seriously lacking for decades, lack of rigour in clinical assessments, health policy restraints, protocols etc., could add up to someone being diagnosed as having ME, when they are iron deficient.
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I can see that someone with iron deficiency might be assumed to be depressed or hypochondriac and diagnosed as chronic fatigue - or let's call it ME to give them a name - by a careless physician. Sure, there are careless physicians all over the place. But for a physician who actually thinks there is a specific condition called ME/CFS I would be surprised if they would mistake iron deficiency for it. The CDC is probably just covering its back.

I am assuming that we are dealing with a competent physician. Th physician in the opening post looks to me to be someone blinkered by a hobby horse interest. A competent physician genuinely interested in the problem confusion of iron deficiency without anaemia with other things would have done a more professional piece.
 
I was also diagnosed several times with low ferritin while HB was normal.

A well meaning non ME doctor thought to have found the reason for my "fatigue" and put me on iron IVs. They did raise ferritin for a short period of time and then it always dropped again quickly.

Ferritin levels never correlated with severity of my symptoms so I gave up on it but it's probably good to check again anyways.

Edit: A ME doc told me as a hypothesis later that, if I remember correctly, the body might try to keep ferritin down to not feed the pathological process that's going on in ME.

This happens with another mineral or vitamin in another illness, I dont remember what it was called..but you're then not supposed to substitute it.
 
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Jonathan Edwards said:
I can see that someone with iron deficiency might be assumed to be depressed or hypochondriac and diagnosed as chronic fatigue - or let's call it ME to give them a name - by a careless physician. Sure, there are careless physicians all over the place. But for a physician who actually thinks there is a specific condition called ME/CFS I would be surprised if they would mistake iron deficiency for it. The CDC is probably just covering its back.

I am assuming that we are dealing with a competent physician. Th physician in the opening post looks to me to be someone blinkered by a hobby horse interest. A competent physician genuinely interested in the problem confusion of iron deficiency without anaemia with other things would have done a more professional piece.
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Thank you @Jonathan Edwards
 
Leila said:
I was also diagnosed several times with low ferritin while HB was normal.

A well meaning non ME doctor thought to have found the reason for my "fatigue" and put me on iron IVs. They did raise ferritin for a short period of time and then it always dropped again quickly.

Ferritin levels never correlated with severity of my symptoms so I gave up on it but it's probably good to check again anyways.

Edit: A ME doc told me as a hypothesis later that, if I remember correctly, the body might try to keep ferritin down to not feed the pathological process that's going on in ME.

This happens with another mineral or vitamin in another illness, I dont remember what it was called..but you're then not supposed to substitute it.
Click to expand...

@Leila your info is interesting. I wonder how many Members have had iron deficiency and/or iron deficiency anemia since being diagnosed as having ME. I also wonder if pwME don't utilize iron very well; or some may have food insecurity and have a less nutritious diet, or have food sensitivities, or other things, the list could go on.

:)
 
About the separation of iron deficiency from iron deficiency anemia, I wonder why the separation in the first place. Why were these two seemingly related conditions separated?

As said earlier, ferritin level seems to be a second string consideration if hemoglobin is OK.

This may create some problems: treatment delays, wasted time and health care funds pursuing other avenues, misdiagnoses etc. And in the meantime the patient isn't feeling any better.
 
DokaGirl said:
About the separation of iron deficiency from iron deficiency anemia, I wonder why the separation in the first place. Why were these two seemingly related conditions separated?

As said earlier, ferritin level seems to be a second string consideration if hemoglobin is OK.

This may create some problems: treatment delays, wasted time and health care funds pursuing other avenues, misdiagnoses etc. And in the meantime the patient isn't feeling any better.
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I wonder why iron deficiency and iron deficiency anaemia are separated as well. My iron and iron-related results tend to be inconsistent - in the past I've had, for example, one measure suggesting I have enough iron and another will suggest I have far too little. Since ferritin is an acute phase protein any infection or inflammation is likely to raise it i.e. the body will store iron in ferritin to help reduce the chance of a pathogen getting access to your iron. (Pathogens need iron to reproduce, like most organisms.) So people can be ill with an infection, for example, and their ferritin may look okay or quite good. But the iron levels in serum could be very low indeed.

So how do doctors interpret okay levels of ferritin and below range serum iron? In my experience they don't, because they almost never test serum iron. But it could indicate infection or inflammation that should be investigated.

A problem I have that I simply don't understand is my TIBC. If it is low it is supposed to indicate that iron levels are good, or possibly even high. But I've had TIBC which is substantially under the range with serum iron which is under the range and ferritin which is very low in range. I had been suffering from a GI bleed for several years at the time. But even after that was fixed my TIBC has a tendency to drop when my levels of iron are low. And it really shouldn't according to the reading I've done.
 
I've struggled with anaemia on and off since I was a kid.

Even without overt anaemia my HBC is at the very low end of "normal". My ferritin stores are always below normal. I have yet to find an iron supplement I can tolerate when taken as directed for more than a couple of weeks.

Even if I do struggle on and get iron levels to low "normal" they tend to drop back again quickly, even with a diet optimised for iron absorption.

I am not permitted IV iron as I have been told the risk of adverse reaction is simply too high - even with the newer safer product.

I wonder if it's related but I also struggle with other trace elements such as manganese, chromium, zinc, magnesium etc.

Jonathan Edwards said:
My own experience with people who were seriously iron deficient and anaemic with it is that fatigue was not an issue. In most cases I was seeing them for something else and iron deficiency came up on tests or they were pale.
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Thanks for that comment @Jonathan Edwards. I've often wondered if I could push the iron levels up would I feel enough of a significant improvement to feel different.

I've discussed taking steroids as a safety precaution pre IV iron but even so, no doc is prepared to take the risk even when I have. Sounds like it probably wouldn't be worth it anyway.

Leila said:
Edit: A ME doc told me as a hypothesis later that, if I remember correctly, the body might try to keep ferritin down to not feed the pathological process that's going on in ME.
Click to expand...

Interesting notion.
 
Leila said:
Edit: A ME doc told me as a hypothesis later that, if I remember correctly, the body might try to keep ferritin down to not feed the pathological process that's going on in ME.
Click to expand...

That doctor needs to do some revision on ferritin. Pathogens can access free iron in the blood stream, and this helps them to reproduce. But they can't access iron which is stored in ferritin. So the body stores as much iron as possible in ferritin (in cases of infection/inflammation) and leaves as little as possible as free iron.

See page 8 in this newsletter : https://web.archive.org/web/2020021...ers.org/Websites/idi/Images/4QTR2008FINAL.pdf
 
Invisible Woman said:
Even if I do struggle on and get iron levels to low "normal" they tend to drop back again quickly, even with a diet optimised for iron absorption.
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I have never understood why doctors would assume that giving someone iron to raise a low level will fix anything very much for very long. If someone has low iron/ferritin it must be for a reason. Just giving people iron supplements doesn't fix that reason it just raises the numbers temporarily. Whatever caused iron/ferritin to drop in the first place will do it again... and again... and again... each time the patient raises their levels for a while, then stops their supplements.

I am not suggesting that people shouldn't raise their iron and ferritin if they are both low. But once iron/ferritin have been raised to better levels the dose needs to be reduced so that iron levels can be maintained but not allowed to go up or down. Ideally of course, it would be good to find out why iron/ferritin were low in the first place. But that very rarely seems to happen.

Jonathan Edwards said:
My own experience with people who were seriously iron deficient and anaemic with it is that fatigue was not an issue.
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In my own experience of very low iron, fatigue and breathlessness were the two main symptoms. When it got really, really bad I got tachycardia and excruciating chest pain too.

Jonathan Edwards said:
I am assuming that we are dealing with a competent physician.
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Unfortunately, patients can't always assume that. I have, more than once, gone into a doctor's surgery for an appointment, the doctor barely glances at me, looks at his computer almost the entire time, then "Computer says No".
 
Arnie Pye said:
I have never understood why doctors would assume that giving someone iron to raise a low level will fix anything very much for very long. If someone has low iron/ferritin it must be for a reason. Just giving people iron supplements doesn't fix that reason it just raises the numbers temporarily. Whatever caused iron/ferritin to drop in the first place will do it again... and again... and again... each time the patient raises their levels for a while, then stops their supplements.
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Because they don't ruddy well listen I expect.

Every time a new doc realized my iron & ferritin stores were low they were Aha! We can fix that! Very common in women of menstruating age.

When I pointed out I have tried virtually every iron supplement you can think of I was assured but this one will work. Only to be told to take a fairly common product that didn't help. Again.

Made no difference pointing out that like many hypothyroid women my periods were generally quite light.

Apart from.the odd occasion when there was some concern over coeliac disease, which I don't have, it was never particularly connected to anything else.

As @Mij mentioned there's definitely an absorption issue as far as I'm concerned.
 
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