Why?

[ElizabethL]

Hi. I have had fatigue for my entire life to some extent. I am a 46 yo female. I was diagnosed with Hashimotos at 19. Recently I experienced some extreme fatigue and tingling in hands and feet. I asked to be tested for B12 since my mother had PA and Hashi's. Was given an endoscopy and colonoscopy to rule out gut issues. No inflammation and biopsies were normal. I am guessing they did not show IF antibodies. I eat a healthy diet and have no clue what could make B!2 drop to 211. I am to see a hematologist but am worries there won't be a determined cause. Any advice?

[Secondchance]

Hi there are lots of causes. Are you on any drugs? Were you tested for parietal cell antibodies and coeliac disease too?

[ElizabethL in reply to Secondchance]

I have taken Synthroid for all these years. Recently, however, it went through as generic. As well, the maufacturer changed. After three months, my levels made me hyperthyroid. Dose was lowered and changed to Synthroid, but I was then back to being hypothyroid. Bumped to original amount and levels are normal.

My biopsies were tested for celiac and parietal cells. Both were normal. This is my concern. Everything seems like PA (family history, symptoms) but no antibodies.

Thanks for the reply! I really love this group!

[Gambit62 Administrator]

The test for IFA is not particularly sensitive so a negative result doesn't necessarily mean you don't have PA. it's about 50% accurate so you can have the test done several times before you get a positive result.

It is good to know that the the investigations in your gut haven't thrown anything up.

There are a lot of possible causes of malabsorption

PA in the true sense is the most well known - and as it runs in families, despite the IFA coming back negative - given that there are problems with the sensitivity of the test - would still be the front runner.

Other causes include

- gastric surgery affecting the ileum (which is where most of the B12 absorbed from food is absorbed) or genetic deformities affecting the ileum - though the procedures you've already had would seem to rule that out.

- a number of drug interactions - eg anti-acid treatments, NSAIDs, some anti-convulsives (eg Gabapentin - which is also used to treat pain), Metformin - used to treat type 2 diabetes - it is quite a long list

- changes (lowering) in acidity levels in the gut - which generally happens as you get older.

About 1% of B12 is absorbed passively - outside the ileum - and the body is quite good at recycling B12 (though that also involves using the ileum) so it can take a very long time for a B12 deficiency to develop, ie you could have had problems for years or even decades going on in the background - though because the ileum is involved in the recycling as the malabsorption starts to take hold levels will tend to drop faster and faster.

From what you say about diet it should be quite clear that the problem is malabsorption of some sort and not your diet in which case the treatment is the same whatever the cause.

As you have neurological symptoms - the tingling you mention (result of not having enough B12 to properly maintain the insulating lining around your nerve cells) - it is quite important that you get treatment sooner rather than later as left to long the damage may become irreversible.

Overall my advice would be to focus on getting better rather than worrying about what is causing you problems absorbing B12.

Normal treatment is B12 injections - though which form of B12 (usually either cyano-or hydroxo-) and what frequency will depend on where you are located. If you are in the UK then the NICE guidance - in the case of neurological involvement is shots every other day until you stop experiencing any improvement - followed by maintenance shots every other month. (However, a significant number of people seem to need more B12 and even different forms of B12 so that may not be the end of things).

211 may be in the normal range but it is certainly in the grey area where significant numbers of people show symptoms - as the serum B12 test is not specific enough as it looks at all forms of B12 not just the active form that your body uses. raised MMA and homocysteine are ancillary tests that can help to clarify the position where B12 is in the grey area but the guidance is to treat on basis of symptoms not test results.

some references on guidelines relevant in the UK:

bcshguidelines.com/document... - specifically the summary

ukneqas-haematinics.org.uk/...

in terms of clearly stating that the test is not the be all and end all of diagnosis

cks.nice.org.uk/anaemia-b12...

NICE guidelines though they are not very well written and can be quite confusing as the emphasis is on anaemia though that is one symptom and not one that is always present.

Unfortunately getting the treatment you need can be quite a battle - particularly difficult when the condition leaves you so tired that fighting is the last thing that you need.

[ElizabethL in reply to Gambit62]

Thank you so very much! It has been a battle. For about four years, I have tried to pin down my fatigue despite normal TSH etc. Something clicked about my mother's symptoms of PA before diagnosis. I had to ask for a B12 blood test. Wonder if doctors would ever have thought to do so.

Thank you for the perspective that focusing on treatment is where my energy should go. I think I feel like I need to do the extra research on my own as my trust in doctors is a bit low. Perhaps the hematologist will know how to handle it better.

As a side note, I have been taking allergy shots for about the same time as the fatigue became so noticeable. Perhaps a coincidence.

I have had one B12 shot and will do another in a week. Tingling and temple/jaw pain were the only things to subside. Perhaps hair loss has slowed down a bit.

Thanks for all the help! Best regards for your treatment.

[Gambit62 Administrator in reply to ElizabethL]

Not that it matters but are you treating yourself or being treated by GP/Doctor ... totally with you on not really being able to trust GPs - my faith evapourated before I'd even reached my teens when GP put me on tranquilisers aged 11 ... suspect it was to pacify my mother ... instead it probably pacified the garden as most got spat out of my bedroom window when my mother wasn't looking :). That was over 40 years ago.

I don't think it's so much that they don't have all the answers - more that they don't know how to admit that they don't have the answers and generally don't know how to work with patients to find out the answers.

It can take a while for symptoms to recede - it was 9 months into stuff before I consciously noticed any effect from the B12 shots - though that may have been because my diagnosis came out of the blue following a fall that hospitalised me and didn't get any background at all on what B12D meant from doctors there or from my GP (suspect that was lack of awareness of range of symptoms etc). Keep a diary if you can as changes in symptoms can be gradual for some and you don't really notice until you think back later. If you are treating yourself then you may want to think about increasing the frequency of doses. Also good to keep an eye on B9 (folate levels) as you can run out of F9 quite quickly if you are using a lot of B12 and without folate you can't properly absorb and utilise the B12 you have. If you have anaemia then you also need to keep an eye on potassium levels as these can drop during during the early phase of treatment. Banana's are a good source of potassium (and you shouldn't be able to eat so many that your levels go the other way which can also cause problems :)) Folate is best from diet - lots of fruit and veg contains B9.

Some antihistamines/alergy treatments are known to impact on B12 absorption and reabsorption so that could be something that has accelerated things ... ironic that symptoms of B12 include things like acid reflux and alergic type reactions which are then treated just as symptoms with medication that lowers ability to absorb B12 and then things can really start to spiral.

[ollie7horse]

Hi

I was dx with hashis at about same age and then 5yrs ago when i was 45 dx with pa not saying your same but make sure you ask doc if hes checked for intrinsic factor and ask to be tested again also get copy of bloods so yo can see vitd, iron folic acid levels.

Good luck

Ollie

[Polaris]

Hi ElizabethL. You will need to be very assertive as, in many other European countries and Japan, your B12 result would be considered low - deficiencies begin to appear in the cerebral spinal fluid below 550 pg/ml.

In any case, you probably already know that thyroid disease and B12 deficiency are often interlinked and, with your history of PA in the family, severe fatigue and tingling, you should be treated without delay, as "there is a critical window of opportunity before permanent cognitive changes or injury result".

I'm not sure whether this helps but it confirms the connection between PA, thyroid disease and elevated homocysteine:

ncbi.nlm.nih.gov/pubmed/259...

These links give lots of information as well as advice on writing to your GP:

b12deficiency.info/signs-an...

cmim.org/pdf2014/funcion.ph...

Cmim/BMJ document.

Summary

* Vitamin B12 deficiency is a common but serious condition

* Clinical presentation may not be obvious thus leading to complex issues around diagnosis and treatment.

* There is no ideal test to define deficiency and therefore the clinical condition of the patient is of utmost importance."

* There is evidence that new techniques, such as measurement of holotranscobalamin and methylmalonic acid levels seem useful in more accurately defining deficiency.

* If clinical features suggest deficiency, then it is important to treat patients to avoid neurological impairment even if there may be discordance between test results and clinical features.

Severe deficiency shows evidence of bone marrow suppression, clear evidence of neurological features and risk of cardiomyopathy.

It is important to recognise that clinical features of deficiency can manifest without anaemia and also without low serum vitamin B12 levels. In these cases, treatment should still be given without delay."

Very best wishes for a good outcome.

[MariLiz]

I believe on the Thyroid UK website Low B12 is listed as an associated condition. I've heard that having a thyroid condition means our vitamin levels get trashed very easily. Also, we are gradually using more B12 than we are replacing as we age. I have both conditions, plus fibromyalgia. Do hope you get the injections for B12 that you will need. Good luck with the visit to the haematologist. MariLiz