Is the kidney a major storage site for thyroxine as thyroxine glucuronide?

Is the kidney a major storage site for thyroxine as thyroxine glucuronide?

This paper raises some very interesting thoughts -

How does this affect those with compromised kidney(s) or kidney function?

Does this have implications for urinary thyroid testing?

How much of the daily variation in thyroid hormone levels is controlled by the kidney - and how much by the thyroid?

As usual, my brain now hurts...

Thyroid. 2012 Feb;22(2):187-91. doi: 10.1089/thy.2011.0307. Epub 2011 Dec 16.

Is the kidney a major storage site for thyroxine as thyroxine glucuronide?

Buitendijk M, Galton VA.

Source

Department of Physiology and Neurobiology, Dartmouth Medical School, Lebanon, New Hampshire 03756, USA.

Abstract

BACKGROUND:

Previous studies have shown that thyroxine (T4) is stored as T4 glucuronide (T4G) in the kidney, and that 24 hours after administration of [(125)I]T4 to mice, 17% of the radioactivity was present in the kidneys, whereas only 4% was found in the liver. The present study was carried out to determine the relative amounts of conjugated and unconjugated T4 and 3,5,3'-triiodothyronine (T3) in the kidney and liver, and whether the conjugated hormones are extracted from tissues using our established extraction protocols, and detected in our radioimmunoassays (RIAs) for T4 and T3.

METHODS:

Mice were injected with 10?µCi [(125)I]T4 or [(125)I]T3 and 24 hours later, the labeled compounds present in serum, kidney, liver, and urine were extracted and analyzed by paper chromatography before and after treatment with ß-glucuronidase. In addition, the amounts of endogenous T4 and T3 in extracts of mouse kidney and liver were measured by RIA before and after treatment with ß-glucuronidase.

RESULTS:

After [(125)I]T4, more than 95% of the total kidney and liver radioactivity was extracted, and in the kidney, almost all of it was present in a conjugated form, mostly as T4G. The liver also contained T4G, but none was present in serum or urine. T3 glucuronide (T3G) was also found in the kidney and liver after the administration of [(125)I]T3. Analysis by RIA of the endogenous T4 content in extracts of kidney before and after hydrolysis by ß-glucuronidase revealed that a substantial fraction of the T4 in both tissues was present as T4G, and the T4G was not detected in the RIA. Furthermore, the combined T4+T4G content in the kidney expressed per gram of tissue was significantly higher than that in the liver or serum. In contrast, the kidney content of T3+T3G was very low compared with that of T4+T4G.

CONCLUSIONS:

In summary, we have shown that the kidney stores a significant amount of T4 as T4G. Since T4G deconjugation can occur rapidly in the kidney, it is possible that this tissue participates in maintaining extrathyroidal serum T4 homeostasis.

PMID:

22175240

[PubMed - indexed for MEDLINE]

PMCID:

PMC3271371

Free PMC Article

ncbi.nlm.nih.gov/pubmed/221...

ncbi.nlm.nih.gov/pmc/articl...

Rod

Picture is from the paper - read Figure 1!

31 Replies

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  • In the 1990's a neighbour who took thyroxine for her underactive thyroid and never had much energy or oomph and mostly looked unwell told me that she went for yearly routine kidney function checks because she had an underactive thyroid.

    My Mother who was hypothyroid and taking thyroxine (previously NDT) never had such checks nor has it ever been mentioned to me.

    I have been meaning to ask on here for over a year and partly expected it to come up in posts.

    Perhaps this thinking comes and goes out of the expert consciousness.

  • yes they check itthrough blood tests to find out if you got addisons disease that hypo suffers can get something to do with cortisone levels linked to the kidneys. can lead to serious problems.

  • ....and in Eastern Medicine the Thyroid and the Kidneys are on the same Meridian I believe !....trust me to lower the tone !!

    Thanks Rod - such an informative post as always :-)

  • Yes, the kidney meridian is to do with the chi or essence of life force.Thyroid and adrenal problems cause the kidney meridian to have energy blockages.I can't explain it properly but when I have acupuncture I am always told that i have weak kidney energy-despite armour thyroid!

  • Very interesting. Having under active thyroid, that was no issue when I wanted to donate one of my kidneys, which I did three years ago. I was not negatively affected by this. So one assumes the remaining kidney takes over enough.

  • That is certainly the theory for everything else re running on one kidney.

    I suspect that you simply have lower capacity for storing T4G. What is not at all clear is what impact that would or could have.

    Rod

  • Interesting that you were able to donate a kidney....when we're not allowed to donate blood.....wonder why???

  • Who is not allowed to donate blood, and why?

  • I've always been told that because I am HypoT that I've not been able to donate blood.....I just assumed it was in case of autoimmune antibodies, tbh, I've never questioned why, just accepted it

  • I am hypo and have donated blood regulary for many years and they know of my health issues and the medications I take and it is fine. In fact in a few weeks I am off to Oxford to take part in a trial where I donate blood more often to see if this is something that can go nationwide, they would not accept me for that if there was a problem. Go to blood.co.uk and ring them up and ask why you were told that.

  • Interestingly enough I have just rung them, & they dont know! lol! I have been put through to a specialist who wants to check it out & call me back in a day or so....he did say it may have been due to autoantibodies, so will find out more when he calls back...most odd

  • Tell him you have spoken to someone who not only is hypo (which they know all about and the medications she is taking, T3 and T4) but she also donated a kidney in 2010 and is taking part in the blood trial that is going on at the moment. So if she can donate blood, so can you, lol .... let us know what they say ....

  • Hi Rod

    This is certainly very important to me as I had one kidney out in November last year. I was slightly hypo before surgery and the hypo symptoms were unchanged for 2 mts after surgery and then had a huge crash with my TSH going sky high. That could be the explanation then! I was never told about any link btwn the 2 organs before surgery and due to being so hypothyroid my GFR was down to 31 in March. GP was very worried but had no idea that my hypo was causing the low GFR. I had to read up about it myself and tell her(just cant believe how poor the care have been had after this surgery ie endocrinology). My thyroid function is up and my GFR is much better(last 49). This just shows the close link that most hypo people are not aware of until they get a problem with kidneys. I don't quite understand the research article and I don't understand the implication for me yet but I will find out!!!!(because the drs certainly wont tell me)

    Roslinxx

  • Low GFR is so very common in hypothyroidism. Many never have a problem, but plenty have a bit of a question mark.

    And GFR often recovers to some extent, as yours has.

    I do not understand the implications.

    Rod

  • I was told not to take magnesium as low GFR would cause it to build up in the body. If many have low GFR should that not be a consideration before taking it. I realise that the issue with the kidney as a storage organ for T4 is different problem for me ( and may not have anything to do with GFR as such). Anyway, what makes me most cross is that this was never mentioned to me and that the GP didn't seem to have a clue.

    Roslinxx

  • Sorry for being dense but what is GFR?

  • Glomerular filtration rate, describes the flow rate of filtered fluid through the kidney. measured as mL/min/1.73 m2

    Table 1. Stages of Chronic Kidney Disease

    1Slight kidney damage with normal or increased filtrationMore than 90

    2Mild decrease in kidney function60 to 89

    3Moderate decrease in kidney function30 to 59

    4Severe decrease in kidney function15 to 29

    5Kidney failureLess than 15 (or dialysis)

    You also have to have other signs and symptoms to have the diagnosis of having Chronic kidney disease

    roslinxx

  • Would a gp usually let me have the GFR test as a 'routine test' w all the others?or do u need v specific symptoms..

  • Routine tests would include kidney function and liver function but it depends on the GP. You could always ask to have it done?

    Roslinxx

  • Hi Roslin, thanks for explaining this x

  • Where do the adrenals come in all this?

    They are really important to thyroid action and are right on top of the kidneys.

    On the Mg retention- my GFR is not great having been on diuretics 15yrs, for a start, but still just off the bottom limit [after long term low level supplementing of Mg Cit.] when it was checked a few months back.

    I've just started 25ug. levo today - so will report here for sure.

    Sad, your experience of Drs- all too common. The first thing mine said yesterday was 'What did I think was wrong' and when I said subclinical hypo [agreed] refused, initially, to treat.

    If I need T3 I will propbably have another battle- but will go for Cortisol and RT3 private checks as well. This site is a real help and I try to give back what I can, too.

    We WILL get on top of these thyroid issues- and wake the medical pros up!

    Long time needed...

  • I suspect that, though highly relevant to everyone, they do not figure in this specific issue. However I could easily be wrong but that will await further research, I fear.

    Rod

  • Many thanks Rod for this article - Have read it twice and next will try to engage science brain even more fully!

    I had a kidney removed in 1995, aged 38, due to obstruction. At no point was my GFR a concern so it was only when I went for a gynae scan that the real truth was revealed - a major obstruction ( of what I still dont know tissue or stones) which I had had since childhood, had caused prolonged extreme thinning of the kidney walls and increased size as it did not drain at all. No wonder pregnancy was a struggle!

    I was hyper I think, before and after the op and then declined suddenly 5 years later. It took 7 years to be diagnosed as hypo.

    Dr P says kidney removal will always compromise the adrenal function - understandably. I was extremely ill on Levo seems to be a processing problem due to adrenal insufficiency. The NHS synacthen test of course says I'm fine.

    I take NAX and NA to support adrenal function and am still trialling T3 to find an optimum dose.

    I have not tried NDT ------- yet !

    Roslin's comment re magnesium is interesting as I had been wondering whether it could be helpful.

    As far as I understand MandyJay's experience of one kidney is more positive because her removed kidney was healthy and had not left other issues so her remaining kidney could take over. I know other donors who have found to same. The specialist said I'd be fine as you can manage on only 2/3 kidney function ha ha.

    As for Marz - you'd laugh - at this moment I have a seed taped to my mid back by my physio at the adrenal acupuncture point. I cant say I have more energy but I can say my constant back pain is improved Yay !

    Now to walk around the garden before engaging brain.

    Regards

    Sarah x

  • In case I was unclear, what I meant was simply that I do not see why there should be a specific association between the T4G storage and adrenals. Absolutely agree that once a kidney goes wrong, including blood supply to it, etc., then adrenal insufficiency is a very likely consequence.

    Thinking a bit more, am wondering if the T4G issue is very largely that normal TT4 and FT4 management use that T4G as a reservoir simply to be able to keep the levels right.

    But what a complex system this simple thyroid disorder is!

    There is also the often-ignored sulphation process...

    Rod

  • mmmm

    "Thinking a bit more, am wondering if the T4G issue is very largely that normal TT4 and FT4 management use that T4G as a reservoir simply to be able to keep the levels right."

    that's how I see it

    can you say about the sulphation process that would be interesting too - thanks!

  • This is far, far more than I know:

    Under these conditions, T3 sulfate (T3S) may function as a reservoir of inactive hormone from which active T3 may be recovered by action of tissue sulfatases and bacterial sulfatases in the intestine

    thyroidmanager.org/chapter/...

    I do wonder whether failure of this process (for any reason) is a reason for some people needing very much higher levels of T3 than others. (Or, indeed, of T4.) Let us suggest that such people are failing to secrete appropriate levels of sulfatases?

    Rod

  • Yes, I was referring to that train of events, Rod - where adrenals are compromised.

    I was wondering at the same time why they are on the kidneys, in any case?

  • There was no space left when everything else had been fitted. So they thought, as the kidneys were slightly bigger than needed, they could take a tiny bit off the top of the kidneys and put them there. :-)

    I do agree - the kidneys do seem to far, far more functionality than "filtering/extracting waste from blood" - and all too often seems to be ignored. And it is always fascinating to consider how things are linked in odd ways.

    One oddity, fish thyroid tissue can be distributed through their bodies.

    I wonder if any animals have adrenals other than right next to kidneys? And,if so,what would they be called?

    Rod

  • Could be worth some inspection- but my brain is fagged out just now ;)

    I suppose kidneys are not glands -so with hormone issues the adrenals are the babies to take care of!

    I know BP meds have a big impact on hormones and water/electrolite balance via the kidneys and why a weather eye is kept out for GFR under treatments.

  • 2yrs ago i was diagnosed with a kidney not draining properly only 22percent i have had an underactive thyroid for 10 yrs and been on levothyroxine at differing doses i have recently been having hot flushes and night sweats i am 76 by the way, generally feeling unwell have had thyroid blood test and was told its perfectly ok stay on the same dose i am now wondering if my kidney problem and thyroid are linked the specialist wanted to take ou the affected kidney but i had a dislocated hip join and back problems so he has put it off for another year but nobody has linked the two things together i did not know i had a kidney problem it was discovered from a routine blood test, i do not think gp,s know enough about thyroid the comments on this page have helped me understand better

  • Hi I have not been diagnosed with under active thyroid but do have a lot of symptoms I recently had routine blood tests done all of which came back normal. I am feeling pretty rough at the moment feeling off balance really bad night sweats and a pain in my back. If it was a kidney problem would it show up in blood test

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