Question about globulins

[mermaid]

I am trying to get my head around the blood tests that I have had recently and whether low globulins are likely to be related to my immune problems?

I had a liver test and my globulin was low in that (all other in the test OK). I also had a bone test and that also was fine apart from the low globulin. I also have low platelets and these have been ongoing low for a few years now, but are the lowest they have been for 4 years. My immune system has been really struggling this year, but last year was the best it's been with all my results in range.

I have a theory on the cause of this......I take Liothyronine/T3, and last October an Endocrinologist asked me to reduce my dose and since then my immune system has been sliding down, made worse in the past few weeks by also being asked to take Thyroxine/T4 with my T3. I now have a constant sore throat. They are worried that my osteoporosis is being caused by the T3, but if I have to suffer a dodgy immune system instead then I am not much better off.

 

[evlee8856]

Hi Mermaid,
I'm brand new here. In fact, this is my very first post, so I apologize in advance if my response not quite the norm. I also have low globulins. My A/G ratio is usually 2.4- 2.6.

I also have Hashimoto's and take Synthroid. My thyroid is misbehaving and my TSH is trending between .004 and 18 (seriously), with a typical value of 2 over the last 2 weeks. However, my Thyroid Peroxidase is 283. So, as you can see, it's under attack. I know that I deal with sore throats every time it swings drastically one way or the other. I also have Osteoporosis due to a surgical hysterectomy w/o hormone replacement at 27 years old (at least we think thats the reason) and my Vitamin D with 50,000 IU weekly trends at 27. I've never heard anything about my thyroid effecting the Osteoporosis. I don't know if that's helpful or not. However, My stomach has a whole other autoimmune issue (Pernicious Anemia requiring B12 injections) thing going on. I'm only mentioning this because it makes it difficult for my body to absorb my Vitamin D and my thyroid medication, and my Vitamins. How's your tummy? Have they checked your B-12? Are you healthy otherwise? When you say dodgy immune system, do you get sick easily? Sorry for all the questions, I'd just love to connect and give support (not medical advice because I am not a doctor) but I deal with several AI issues as well as Isolated IgM deficiency.

 

[mermaid]

Hi Mermaid,
I'm brand new here. In fact, this is my very first post, so I apologize in advance if my response not quite the norm. I also have low globulins. My A/G ratio is usually 2.4- 2.6.

I also have Hashimoto's and take Synthroid. My thyroid is misbehaving and my TSH is trending between .004 and 18 (seriously), with a typical value of 2 over the last 2 weeks. However, my Thyroid Peroxidase is 283. So, as you can see, it's under attack. I know that I deal with sore throats every time it swings drastically one way or the other. I also have Osteoporosis due to a surgical hysterectomy w/o hormone replacement at 27 years old (at least we think thats the reason) and my Vitamin D with 50,000 IU weekly trends at 27. I've never heard anything about my thyroid effecting the Osteoporosis. I don't know if that's helpful or not. However, My stomach has a whole other autoimmune issue (Pernicious Anemia requiring B12 injections) thing going on. I'm only mentioning this because it makes it difficult for my body to absorb my Vitamin D and my thyroid medication, and my Vitamins. How's your tummy? Have they checked your B-12? Are you healthy otherwise? When you say dodgy immune system, do you get sick easily? Sorry for all the questions, I'd just love to connect and give support (not medical advice because I am not a doctor) but I deal with several AI issues as well as Isolated IgM deficiency.

Thank you for replying @evlee8856 and welcome to the forum! It is so interesting to compare things with other sufferers and to try and understand what is going on. I am so sorry that you find yourself with osteoporosis also - are you still 27? That is very young to develop that condition, and I had no idea until I went on osteoporosis forums that there were so many pre-menopause with it.

I am comparatively much older, and osteoporosis is not quite so unusual at my age (65) although I have been told that it's more normal at my age to have osteopenia.

They suspect the thyroid medication because I am not on T4/Thyroxine (the equivalent of Synthroid as I am in the UK), although I was for 17 years, but due to all the problems I was having, I persuaded an Endocrinologist to let me try T3/Liothyronine for 4 years, having first tried it mixed with T4 for a short while. When you on quite a bit of T3 then the TSH becomes suppressed, and the Endos then worry as some research has indicated that a suppressed TSH = possible risks from osteoporosis or atrial fibrillation. However the patient communities completely disagree with this, as long as there are no other signs of overdosing (e.g. high BP, pulse or temperature and I had none of these).

The problem with the UK is that many of us only see our GP to manage our thyroid and they don't have much clue about any of it. As for the endocrinologists, well they have very rigid views of things, made worse by the fact that Liothyronine prices have been artificially inflated by the only pharmaceutical company who produces it, so they are desperate to get patients off it, so I am in a tricky position over it now. I have agreed to try adding some T4 to some T3 to see how I do but I am not doing well on it so far. If you use T4 then the body has to convert it into T3 to work in the cells, and some people don't convert well, or there are thyroid transport issues but the Endos don't seem to understand this issue or care! Very little testing going on that you describe too. I do get tests if I ask for them from my GP but she doesn't know what to do with them.

Your situation sounds tricky at the moment. Has anyone suggested that you try to stop eating gluten as apparently that can make the attacks worse for some people? I stopped gluten some 5 years ago, and gave up most sugar. However you could well be right that it's my thyroid under attack as I have had this sore throat issue a lot over the years.

I am fairly sure that I don't have Pernicious Anaemia - at least the standard B12 tests don't seem to indicate that. I did inject myself with B12 a couple of times on the advice of an ME/CFS Dr and it never seemed to make much difference, plus my energy levels are usually quite reasonable for someone with ME/CFS. I do take oral B12 now to be sure.

I do have stomach problems though, but can manage them reasonably well and have had a lot of tests done both on the NHS (free) and privately and it only threw up Non Ulcer Dyspepsia and IBS issues. By avoiding certain foods I can generally keep the symptoms under good control.

I have also had Vit D testing done twice privately and had good results, although I do take Vit D3 supplements to ensure it's good. So there's no sign that I am not absorbing.

I did read something about low globulins can mean however that protein is not digested or absorbed properly. However I would not have thought this would give me sore throats! It seems more likely that my immune system is compromised in some way. Last year all of my markers were normal and this was before I was asked to reduce my thyroid meds, which is why I think it's because I am now not getting what I need, although I also think that the herbal medicine I take also helped.

By 'dodgy immune system' I mean that I frequently feel like I am fighting off a virus, usually with a sore throat or other symptoms. I don't usually feel like this so much in summer though, which is worrying me. I rarely get anything very serious though (I did have a chest infection a couple of years ago) maybe because I use Oil of Oregano the minute I get something. I have had the Immunoglobulins tested in the past at my request, and I need to have them done again I think. One of them was low (IgA I think) but not drastically but it was a while ago now.

Anyway, sorry this is a really long reply!!

 

[Gingergrrl]

However, My stomach has a whole other autoimmune issue (Pernicious Anemia requiring B12 injections) thing going on.

Hi @evlee8856 and welcome to PR. I was curious how you found out that you had pernicious anemia and what your symptoms were? Were they actual stomach/GI symptoms or did you find out b/c you tested low for B-12 on a blood test and then tested for pernicious anemia?

How do you tolerate the B-12 shots and have they raised your B-12 levels or improved your symptoms? I also have Hashimoto's (amongst other problems!) but I take Armour vs. Synthroid and my thyroid numbers (except for the two Hashi's auto-antibodies) are normal on the med.

I am trying to get my head around the blood tests that I have had recently and whether low globulins are likely to be related to my immune problems?

@mermaid, are you considering IVIG for immune deficiency (or asking for another reason)? I am autoimmune and do high dose IVIG but know a lot about it now in case I can be of any help.

 

[mermaid]

@mermaid, are you considering IVIG for immune deficiency (or asking for another reason)? I am autoimmune and do high dose IVIG but know a lot about it now in case I can be of any help.

Hello Gingergirl
Thank you for your reply. Not sure if I have the quote thing right - I can rarely get my head around how to do it!

I doubt that they would consider IVIG for a case like mine as I don't think they would consider it bad enough yet although it seems to be chronic rather than severe. It's just that no one has ever explained what the low globulin result on my tests actually means!

I have googled it, but it seems it can mean a number of things. The Dr doesn't actually test me unless I request it but mostly when I have a liver test the low globulin result is there and this time when I had the bone test it also had low globulin. As I struggle with my immune system I am guessing that it's connected. I constantly pick up low grade type of infections especially in the winter, but am getting them in the summer this year too which is unusual for me.

I have had the Immunoglobulin test done once I think, and that was a bit off but not markedly so. The low platelets are pretty consistent, and are a bit worse at present. I had low platelets in pregnancy many years ago, and I gather that is considered autoimmune (thrombocytopenia) but my current level is not as low as then.

Do people with autoimmune disease tend to have low globulin results? I know I have at least one autoimmune disease (underactive thyroid) and probably Lichen Planus is autoimmune, plus the issue of the platelets.

 

[Gingergrrl]

Hello Gingergirl Thank you for your reply. Not sure if I have the quote thing right - I can rarely get my head around how to do it!

It looks like you did the quote correct to me!

I doubt that they would consider IVIG for a case like mine as I don't think they would consider it bad enough yet although it seems to be chronic rather than severe. It's just that no one has ever explained what the low globulin result on my tests actually means!

I re-read your post more carefully and I was initially thinking that you were talking about the IGG total and subclasses test (and low IGG is often used as a reason for IVIG for immune deficiency). In my case, it did not apply, b/c I got IVIG approved for autoimmunity.

In re-reading your post this morning, I realized (if I understand this correctly, which I may not), that you were talking about the Globulin test which I think I just had a version of with my Endo. The test that I had was called an "A/G Ratio" or "Albumin/Globulin Ratio" and mine was found to be low at 0.9 and the bottom of the range was 1.2 so it was flagged as low.

I Googled what this means (and also inquired about it in another thread when I got all of my abnormal results) and learned from Google that "a low A/G ratio may reflect overproduction of globulins, such as seen in multiple myeloma or autoimmune diseases, or underproduction of albumin, such as may occur with cirrhosis, or selective loss of albumin from the circulation, as may occur with kidney disease (nephrotic syndrome)". In my case, I have autoimmune disease so we are suspecting this is the reason vs. something more sinister and scary.

Do people with autoimmune disease tend to have low globulin results? I know I have at least one autoimmune disease (underactive thyroid) and probably Lichen Planus is autoimmune, plus the issue of the platelets.

Last night I would have said no (b/c I totally misunderstood the test) but now I am thinking that people with autoimmune disease might tend to have low globulin results on the "A/G ratio" test. But I really am not sure in general and hoping that someone with more knowledge than me will reply. I do have Hashimoto's like you (and a bunch of other auto-antibodies) but I do not have Lichen Planus or the low platelets. My latest testing showed that my RBC's, Hematocrit, and WBC's were low and am still trying to sort out what this means.

Are your RBC's or WBC's low or only the platelets? I am going to be tested for pernicious anemia at the end of this week and some other stuff (but overall my doctors were not too concerned... which I guess is good? )

 

[mermaid]

Hello @Gingergirl. I apologise that I did not reply to your post above. I hope you are doing as well as possible now?

Since my post above, my immune system has continued to decline, and I have had 4 colds since the start of July, though none of them serious but just difficult as I get another as soon as one goes. As a result I asked for an immunoglobulin test to be done again (had one last year I think and the year before maybe) - the IgG one that you mention in your post. Last time I had it done I was low in range, but apparently now I am borderline low but am going to try and get my printout on Monday. I am due to see the GP about the result in a few weeks time.

Last year my immune system was in recovery so I am unsure of the reasons, and I doubt my GP would even refer me to an immunologist unless things got worse, but hopefully she will keep an eye on me now. As I understand it, the subclasses tests are usually done by an immunologist rather than a GP here in the UK.

I did suspect the change in thyroid meds, and I am now on even less T3 and more T4 so we will see.... but meanwhile my herbalist has added Astragalus back into my mix, so fingers crossed that it will work for me as she did give it to me a while back. I need to check when she last took it out, as maybe that was the reason I declined.

You asked if I also have low WBC and low RBCs - no I don't, just the low platelets, although I have had low markers on other things in the past, and lymphocytes are often low in range or just below range.

 

[Learner1]

Hi Mermaid,

You will want to have all of your immunoglobulins measured - IgG, IgA, IgM, and IgE, with subclasses.

I too have low globulin and high A/G ratio. My albumin is normal. When originally measured, my total IgG was 702, but I had low IgG subclasses 1 and 3, which are what fight bacterial and viral infections (and are tupically low in ME/CFS). Over the next couple of months, my total went to 605, then 573 and I felt worse and worse.

My doctors also found 4 herpes family infections - Epstein Barr, cytomegalovirus, HHV6, and HSV2, and 2 atypical pneumonia bacterial infections that my body couldn't fight off. These, in turn, created autoimmune adrenergic and muscarinic antibodies, which researchers are finding in a subset of ME/CFS patients, which caused POTS.

From what you've shared, you need to be asking for diagnostic labs of your immune function - there are also cytokines and NK cells that can be tested, as well as looking into possible viral and bacterial infections. There's also autoimmune testing which can identify antibodies if needed.

In the US, total IgG below 700 or multiple low IgG subclasses and a pneumonia vaccine challenge are typically qualifiers for IVIG, intravenous immunoglobulin treatment that some of us get. In my case, due to the autoimmune component, I get a higher autoimmune dose of IVIG, as well as antivirals and antibiotics.

Its likely you have something going on. You must need a good doctor and the right tests.

Best wishes...

 

[mermaid]

Thank you for your info @Learner1 So far I have only had a few immunoglobulin tests done over the past few years, and only at my request. I previously had IgG, IgA and IgM but not the subclasses. I am not sure if the GP can order those or if I would need to be referred to an immunologist. My IgA was below range last time it was checked, and the IgG was only just in range. However I have not had very much severe illness with it recently - just chronic and frequent colds especially this year including the summer which is less usual for me.

Our health system is very different from the U.S. and I will need to see what my GP says when I see her soon over this. I don't quite know why but there are no immunologists at all in my whole county and I would need to travel a couple of hours to see one in the next if they think it's needed. I even looked up private immunologists as I do have some private cover which would cover some things, and even then there were no private ones any nearer to me!

The fact that my immune system seemed to be recovering last year (via the tests I had done which were not comprehensive, but also my symptoms had vastly improved), shows that my body is capable of recovering, but I am not entirely sure why it's now gone backwards. I fear that reducing my T3 thyroid med is in part responsible, but I cannot prove this, and since they also blame the T3 for partly causing my now diagnosed osteoporosis, I am in a bit of a fix over that aspect. I am hoping that the Astragalus will help to pull things back for me and I am great believer in herbal medicine. I find that Oil of Oregano has helped me at other times too.

It's interesting to hear of your own experience and the tests that you have had done, and I hope that things will improve for you too.

I am 65, and if I look back I had quite a history of immune issues as a child (I had pneumonia) and a rather nasty urinary infection, and I remember constant sore throats and colds, all of the various childhood illnesses that we were not immunised against then, and then got glandular fever very severely at aged 13. I was pretty good in my 20s/30s, and early 40s until I developed hypothyroidism, and then it's been downhill since then again.

 

[Learner1]

When I saw my expert CFS doctor, he went through my history back to childhood. He thinks my immune system may have been dysfunctional since birth. He got my IVIG approved by using a code for Common Variable Immune Deficiency. You might look it up and see if it fits you.

IgG subclasses are a cheap test here. I imagine your GP could do it.

He also thinks I have MCAS, mast cell activation syndrome. I recently had a DEXA scan which showed severe osteopenia in my hips, even though I have plenty of calcium and vitamin D, am tall and bigger boned, and have lifted weights for years. I lost 22% of my bone density in 6 years.

My primary doc thought it might be too much thyroid - I have Hashimoto's and had been on T3 only for 4 years due to very high rT3, before switching to T4/T3 a year ago. But my FT3 was midrange and FT4 was low, though TSH has been close to 0 throughout.

However, my CFS doc says my pituitary isn't working due yo other tests, so I'm not going to be making TSH anyway...

I did see that low estrogen and low TSH have been linked to osteopenia and have an appointment with an endocrinologist with an interest in bones soon to see what he says.

However, my CFS doc thinks its a symptom of MCAS, and as I'm writing this broken out in yet another mysterious case of hives, it could well be, though tryptase and histamine have been low. But apparently, they don't have to be high to have MCAS.

So, it might be useful for you to see an immunologist given what you've shsred, or at least print some stuff out from he web and go prod your GP to help you.

Best wishes.

 

[mermaid]

Hello again @Learner1 Sorry not to reply before, but I thought I would wait for my latest Immunoglobulin test to come back before I replied.

I was very interested in what you had to say about your own story, and it sounds as if you have a very supportive and helpful expert CFS doctor there. If only there were some like that in the UK! I did pay to see a private Dr in London a few years back but it got too expensive for me, and also he was so far away, and quite limited in his understanding, although better than someone in our standard free health service.

I did look up the Common Immune Variable Deficiency. I am not sure that I would qualify. I did have a lot of illness as a child, but apart from getting pneumonia once, I don't remember getting anything very serious until I got glandular fever at aged 13. Well I had a lot of sore throats and colds, and childhood illnesses, but I don't remember having a lot of time off in my teens, and my immune issues improved a lot once I left home!

Things began to deteriorate in my late 40s again, but even then it's just kind of low grade stuff that is persistent but not severe. I do use Oil of Oregano at the first sign of anything, and I feel sure that helps me and I have managed to avoid using antibiotics for many years other than for a dying tooth.

Still, my latest test has just come back looking a bit worse and I have now dipped into the just below range with the IgG, and am still below range for IgA (same as 2 years ago). IgM is OK. I do have an appointment to discuss this with my GP now and will ask if she can test the subclasses when I see her and print some stuff out as you suggested - thanks!

I was particularly interested in your thyroid experience with possible regards to your osteopenia, as like you, I was on T3 only for 4 years and also have Hashimotos! I had previously been on T4 only for 17 years, but shortly before I went onto T3 only I happened to have a heel density test done privately and it showed low risk for osteoporosis with -1.1. Then 2 years later I went onto the T4 for the 4 years, and then was sent for a DEXA scan which then showed -3.2 in 2 areas, so that was a bit of a shock as not just osteopenia but osteoporosis. Obviously I cannot be certain about that heel test as it's different to a DEXA, but I have to accept that there may be a link. Patient groups do not agree that T3 usage can lead to osteoporosis and there is a lot of disagreement between patient groups and the 'experts' on the T3 issues I have found.

I am in the midst of going T4/T3 but phasing it in slowly until I end up with just 20mcg T3 and probably 75 of T4 but I am worried that it's adding to the immune problems as I said, as they have got worse since I began to do this journey, but I guess it may settle down again. My hair has fallen badly too.

Are you post menopausal too? (I assume you are female but you may not be of course!). I understand that there can a big loss of bone just past the menopause before it then settles down, however I had been through this phase as by the time I lost the bone I was over 10 years past menopause. Unlike you I did not do weight lifting which I have read is useful for keeping bone, but had done plenty of weight bearing over the years, with walking and gardening, and some dancing.

I am glad to see that your CFS doctor has picked up on your pituitary issues though... I don't know a lot about that although I did have a calcium test done as I believe if it's high that a clue of problems with it and mine was normal. Obviously in my case my oestrogen levels would have fallen a lot and I am 15 years post menopause so a bit late for any kind of hormonal interventions, but I do take bioidentical progesterone now (but have been told it's not enough to help with the bones by someone). I am also taking an array of supplements for the bones now including Boron, and Strontium Citrate, and my herbalist is also giving me some herbs too.

I looked into MCAS myself last year (just researching online not going further) as I had some signs of it. It seems to have settled down thankfully but there was definitely an issue with histamine and I had to stop using Kefir as that was causing me problems, and there were some other histamine problems too. I also had a few odd signs but nothing too much - I didn't have rashes. I try to keep my histamine intake lower and that seems to have solved my problems there.

Thank you for all of your input. Very much appreciated. x

 

[Learner1]

Definitely have IgG subclasses tested. They're likely low if your total is below range. The history you're describing is similar to mine...

I had stage 3 cancer involving uterus and ovaries. Surgically induced menopause + chemo, so I expected some loss, but not 22%! We did some different tests to see if it dated to my cancer treatment, bit they all pointed to current bone loss. Suppressed TSH and low estrogen can lead to osteoporosis, so it's a possibility.

I'm such a scatterbrain these days and have quite a few conversations going on, but if you contact me in mid-October, I can update you on my appointments with the bone knowledgeable endocrinologist and the local immunologist who I'm going to discuss MCAS with.

Thanks for the chat. Let me know when you get your subclasses back, ok? Low 1 and 3 is classic for ME/CFS, but 2 and 4 happen, too. Which ones may affect treatment options.

 

[mermaid]

Hello again @Learner1 Thank you for your reply. Yes, I would be interested to know about your appointments and will try to remember to get back to you in mid October.

That must have been difficult for you having cancer and as you say, that does indicate some bone loss. But as you say 22% is a big drop. I have no idea of how much mine is as a %. I have so little info given to me, other than the basic DEXA and most people here don't even get them until they fracture something!

It is interesting that the patient community who discuss T3 and NDT tend to discount the suppressed TSH causing osteoporosis, or so has been my experience. I have a person who has been supporting me on one thyroid forum telling me categorically that my T3 only usage has not caused it, but I feel that it's my body that is suffering and not hers, and we are all different in our bodies and how they react. No one really knows, and in the UK they are not bothered to find out, other than reducing my t3. As you say, low estrogen doesn't help either and I have no idea on that too, although I am going to ask my GP for a blood test to get some idea.

Anyway, thanks, I will come back to this next month!

 

[Learner1]

Sounds good! I think its much more than thyroid... There's got to be some multivariable equation.

Anyway, I gave seen accounts of reversing osteopenia/osteoporosis, so I am hopeful. Just makes sense that a biological process can go both ways... even older people can have a bone heal after a break...

I'll take notes, and ping me again in a month.

 

[mermaid]

How old are you @Learner1 if you don't mind me asking?

I agree re the multivariables, and no doubt they vary with the person. I suspect collagen issues in myself but that's just on gut instinct.

I am on some FB osteoporosis groups, where people are trying to reverse the process and some are trying without the drugs. I guess it depends on how you feel about them. If you use the drugs it will help with the density but I am not convinced that it will always help re fractures in the longer term and the side effects are not great.

Anyway, I look forward to hearing your next chapter!