Amiodarone Toxicity: The Closest Thing We Have to “Iodine Toxicity”

The writing on this page is a little disjointed because I pasted paragraphs from other writings I’ve done here.

There really isn’t much information available on “Iodine Toxicosis”.  Probably the closest thing we have is Amiodarone Toxicity, which can cause both hyper and hypothyroidism.  So I’m including a discussion of it here to make some comparisons between AT (Amiodarone Toxicity) and what I believe I’ve been experiencing as a result of being floxed.  In my case, it seems as if I’ve become highly sensitive to Iodine and, to the point where at the end of almost five years post flox, I really can’t tolerate it very well, even in microgram amounts.  So this is why I feel I’ve developed something similar to an “Iodine Toxicity”.

For me, even the very small amounts (micrograms) of iodine became “toxic” to my thyroid gland, which greatly affected my symptoms.  I consider myself to have had several major “TH flares”, starting with the March 2010 Cipro flare, then the Nov 2010 flare, then the Dec 2012 flare (lasting well into 2013), and the last flare of August 2014 which resulted in the Subacute Painful Thyroiditis (See the section entitled “My Floxing Timeline” for a timeline and brief discussion of these flares).  With each flare, I became progressively more and more sensitive to iodine overall, and my thyroid gland appears to be more and more sensitive to iodine as well.  Hashi’s is considered to be an “iodine organification problem”.  Subacute Thyroiditis (SAT) appears to be often virally associated, but in rare cases can be iodine induced, and often there are iodine associated problems with the thyroid gland as long as the SAT lasts as well.  I believe the combination of Hashi’s, and eventually the Iodine-induced SAT, pretty much trashed my thyroid gland when it came to iodine metabolism and utilization issues.  At five years post flox, I had been off of thyroid medication for the previous two years, and struggled through “waiting it out” to see if my thyroid gland could recover using various “thyroid-friendly” diets and supplements.  But it became apparent at the end of that period that wasn’t ever going to happen, and that the gland was shot.

In my opinion, my iodine metabolism problems weren’t limited to just the thyroid gland, but in fact, were systemic throughout my body.  My thyroid gland was just the most obvious target of my problems.  Eventually, by the end of almost five years, I felt like none of my cells could tolerate iodine anymore (at least, as long as I had normalized serum levels of TH).  At this point in time, not only did I experience thyroid and thymus gland pain and swelling, the attacks started on my salivary glands as well, with pain and swelling starting in all of them.  Salivary gland cells express iodine transporters quite heavily, taking in iodine and concentrating it well beyond serum levels, and excreting iodine in the saliva.  I’m assuming that either this wasn’t happening anymore, or, alternatively, that an autoimmune reaction against any and all iodine containing cells was occurring in a last-ditch effort to salvage iodine.  In addition, I felt worse with the slightest amount of iodine ingestion or supplementation overall, as if all the cells of my body “shut down” when exposed to it.  At that point in time, I felt that my body and cells desperately needed iodine – either alone, or in the form of thyroid hormone – but couldn’t get it or utilize it properly.

As far as I could tell, no one knows how long TH and/or iodine will last in a body if production of TH stops completely or ingestion of iodine stops completely.   However, studies of thyroidectomized rats have indicated T4/T3 concentrations in most tissues were still present 2-4 months after removal of the thyroid gland, with some rats starting to die only at 6 months post removal.   Iodine storage other than in the form of thyroid hormone is either unknown or unacknowledged; however, a few researchers and practitioners believe there is a storage pool of iodine that exists within tissues of our bodies.  The drug Amiodarone, which is probably the closest thing we have to knowledge about large amounts of ingested iodine in the body, reveals total body iodine stores remain increased for up to 9 months after discontinuation of the drug (thereby implying iodine is stored somewhere).   It is well known by physicians that it takes months for a body to reach sufficient states of equilibrium, for example, when starting TH after being in a long term hypothyroid state.  Conversely, it can take months, if not years, for “insufficiency” to occur, depending on numerous factors affecting the thyroid system in general.

Again, no one really seems to know how much iodine the body actually needs to store in order to remain “iodine sufficient”.  No one really knows how long it takes for the body to run out of this natural “store” of iodine.  Traditionalists believe the thyroid gland and carrier proteins are the only way iodine is “stored” in the body until needed for use.   Given that I experienced the “first half life metabolism” of the iodine I ingested to be about 5-6 hours post, this makes sense.  Yet, there are some who believe that iodine is stored within cells and tissues outside of the thyroid axis.  The existence of the extra-thyroidal NIS/hSMVT/Pendrin system could support this alternative belief.  One particular researcher (Venturi) states that, “In humans, the total amount of iodine is about 25-50 mg and about 50-70 % of total iodine is non-hormonal and it is concentrated, via NIS, in extrathyroidal tissues. Iodine is present, in different concentration, in every organ and tissue of the human body, not just the thyroid gland. So far the list of these iodide-concentrating cells includes: white blood cells, salivary and lacrimal glands, ciliary body of the eye, renal cortex, the pancreas, the liver, gastric, small and large intestinal mucosa, nasopharynx, choroid plexus, skin, adrenal cortex, mammary gland, placenta, uterus and ovary”.

One comparison that could potentially be made to help determine the half life of iodine is the drug Amiodarone.  Amiodarone is a potent antiarrhythmic drug that is used to treat ventricular and supraventricular tachyarrhythmias.  It is a benzofuran-derived, iodine-rich compound with some structural similarity to thyroxine (T4).  It is highly lipid-soluble and is concentrated in the adipose tissue, muscle, liver, lung, and thyroid gland.  The elimination half-life of Amiodarone is highly variable, ranging from 50-100 days;  total body iodine stores remain increased for up to 9 months after discontinuation of the drug (source:  Thyroid Dysfunction Induced by Amiodarone Therapy,  Mini Gopalan, MD; Chief Editor: George T Griffing, MD).  This sentence alone acknowledges that iodine is being stored within the body, and the long half life is in keeping with floxing syndrome cycles as well.  On the other hand, this could be not because of iodine itself, but the fact it’s attached to the other un-natural components of the drug (benzofuran, etc.) that might provide the long elimination half life.  Might it be possible FQ’s are binding to free iodine (either exogenously ingested or endogenously produced) and being stored in the body tissues the same way Amiodarone is during the acute phase of the reaction?  Could this be yet another potential cause of a “thyrotoxicosis – like” reaction in the body without evidence of elevated T3/T4 in the bloodstream to make a diagnosis of this (ie, an iodine toxicosis)?  This question might seem unreasonable to researchers, because there is no evidence that the FQ’s are actually stored anywhere in the body, and the research states that they are eliminated fairly quickly.  Perhaps this is not true for the affected FQ population?  Perhaps the entire molecule is not stored, but portions of it with iodine are stored, and the acute phase of an FQ reaction is so lengthy due to the long half life dissemination of this iodine?

Alternatively, perhaps the FQ’s are displacing Iodine and preventing iodine, either free or attached to tyrosine, from cellular usage  (this might be a more likely scenario).  Certainly it’s known that Mg and Ca can chelate with the FQ’s, decreasing their absorption, and the drug inserts recommend avoiding taking Mg and Ca while taking the FQ’s as a result.  One of the few papers that I could find discussing FQ’s in the context of thyroid hormone is a case study done on an elderly woman showing that the FQ, when taken orally at the same time as oral Levothyroxine, resulted in extremely increased TSH blood levels, along with decreased T4/T3, as long as the FQ was continued   The presumption is that the FQ is binding up the thyroid medication, rendering it unavailable for use.  Separating out the FQ dosage time from the T4 dosage time appeared to resolve this problem.  However, could a similar mechanism be happening with endogenous hormone, or, more significantly, with free iodine, in pre-disposed patients?  Or perhaps the FQ component is affecting some other unknown part of the chain, changing something somewhere, causing iodine to be stored and eliminated slowly?  FQ’s could be acting as analogs for any of the iodothyronines, thyroglobulin, or other aspects of thyroid hormone metabolism as well.

I am not a “fluoride conspiracy” person, and I don’t know how much or little fluoride is contributing to all the ills of society.  On the other hand, I can’t simply ignore the “halide connection” with iodine and fluorine either. Research exists showing bromine will displace iodine within the thyroid gland and other tissues; it’s reasonable to assume this can happen with other halides as well, most notably, fluorine.   I also question as to whether one of the main reasons so many drugs are fluoridated to begin with is basically to exploit the iodine receptors found on most, if not all cells of the body (NIS/hSVMT) — thereby allowing such widespread successful intracellular penetration in the first place.   One of my own hypotheses of FQ toxicity, regardless of the “halide connection”, is that I suspect an iodine deficient person, with a subclinical or clinical iodine-related thyroid problem, is more susceptible to FQ toxicity in general.  But I think the “halide connection” could provide a stronger argument for this particular hypothesis as well.

As an aside, I also think a strong contender of a potential iodine-disrupting mechanism causing or contributing to FQ toxicity could be FQ’s inhibiting or permanently affecting selenoenzymes.  FQ’s will bind to divalent and trivalent cations, and this could easily include selenium.  Selenium is highly concentrated in the thyroid gland, and de-iodinases, the enzymes which remove iodine from iodothyronines, are playing a large role in intracellular iodine homeostasis as well as energy metabolism (creating T3 from T4).  Selenoenzymes also have critical roles in preventing and reversing oxidative damage in the brain and endocrine tissues; they also act as “gatekeepers” to the cells, acting as regulators of cell homeostasis overall, and all five glutathione peroxidases are selenoproteins. Mercury is highly reactive with selenium, and I think there are similarities of FQ toxicity with Mercury toxicity worth noting.

When it comes to Amiodarone toxicity, keep in mind that there is at least one research paper I’ve read that revealed that toxicity was due to the active ingredient benzofuran derivative in Amiodarone and not the iodine itself.  I don’t believe iodide itself is toxic to people (except maybe for those with true anaphylactic allergies), but that some part of iodine metabolism, for example, damage to iodine receptors, is coming into play, making it “look” like iodine is “toxic”.  This damage could easily occur with a number of environmental toxins, including, in my hypotheses, FQ’s.  Many commonly used drugs have fluorine added to them as a way to gain intracellular penetration, and it may be the combination of this halide attached to a xenobiotic that is damaging iodine receptors/transporters, damaging iodine utilization or metabolism, or initiating autoimmunity.  So here is where the “fluoride toxicosis” hypotheses may be coming into play, in particular, given the relatively higher exposure to fluorides modern humans and animals now get relative to what is found naturally in the environment.   In the case of Cipro, a synthetic genotoxic chemotherapeutic agent (the quinolone pharmacore) with a neurotoxic acetylcholine-blocking agent attached (piperazine), may be gaining entrance to human cells via a toxic iodine halide displacer attached (fluorine).  (There may be any number of ways FQ’s gain entrance to our cells; I throw this idea of NIS/hSMVT receptors out as only one possibility).  Iodide requirements are as old as the evolutionary history of life itself, and the body no doubt has multiple pathways and compensatory mechanisms to control homeostasis of this necessary element. Humans around the world have been exposed to both low and high levels of dietary iodine throughout their lives, and for the most part, our body just naturally and automatically deals effectively with the limitations (store in a thyroid gland) and excesses (excrete the rest).  So it’s highly unlikely that iodine “suddenly” becomes “toxic” to us.  It makes more sense to me that if iodine does suddenly become “toxic”, it is more likely due to extenuating circumstances, such as due to all the synthetic toxins masquerading as iodine or utilizing iodine metabolism and homeostasis mechanisms within the body (which includes thyroid hormone metabolism and homeostasis).  If these are autoimmune reactions, autoimmunity may be developing against the foreign xenobiotics attached to iodine or other halides, and then targeting the receptors or other intracellular mechanisms utilizing these xenobiotics or iodine.

Of course, what is truly ironic about Amiodarone, is how all the problems and side effects of it are attributed to the iodine component of this molecule.  Despite the fact that iodine has been absolutely necessary for virtually all life forms to evolve and survive, and humans throughout the ages have had a wide capacity to tolerate both extremely low and extremely high levels of iodine ingestion without a problem, somehow, iodine itself is to blame for any problems with Amiodarone.  No one seems to think that perhaps putting a very un-natural molecule, such as benzofuran (a component of coal tar, by the way), chronically into tissues it should never be in, such as fat, muscle, liver, lung, and thyroid gland tissue, might in fact be the cause of the side effects and problems and toxicities.   There is even a study showing that Amiodarone is toxic to mitochondria, and that the benzofuran moiety, not the iodine, is responsible for this toxicity (Toxicity of amiodarone and amiodarone analogues on isolated rat liver mitochondria).    To top it all off, not only is benzofuran described as a “component of coal tar”, but the quinolones are described as “organic chemical structures that are related to the heteroaromatic coal tar isolate quinoline”, and last but not least, 4-quinolone derivatives are being studied for use as TKI’s (tyrosine kinase inhibitors) – which appear to have thyroid dysfunction as part of their adverse effect profile.   In other words, it appears “coal tar”, a common denominator in both Amiodarone and FQ’s — and FQ-TKI’s — may also be a common denominator in both thyroid and mitochondrial dysfunction, so perhaps this is a link (as an aside, coal tar derivatives have been the basis for several medications historically and are used as food additives as well).   Although there is much interest in using iodine (or another halogen, fluorine) to attach to drugs of interest for transport purposes into cells, there does not seem to be much thought at how those attached drugs might in fact damage the actual iodine transporters themselves, or, of course, any other intracellular reaction (including thyroid cells) that might utilize iodine.

Interestingly enough, it’s assumed that radio-iodine treatment is what “kills cancer”.  I’ve no doubt that radiating anything might “kill it”.  On the other hand, there are a few researchers and physicians who believe that treating some cancers with iodine alone will work, and that cancer is allowed to develop when iodine is scarce.  The most often quoted research for this is how Japanese women who tend to eat an iodine rich traditional diet experience much less breast cancer than women eating the traditional western diet.  This suggests more of a preventative effect.  It would be an interesting study to compare treatment of cancer with iodine alone versus iodine with radiation, although I doubt such a study would ever be done.  Cancerous cells tend to not take up iodine (perhaps this is one reason they are cancerous).  So getting iodine into these cells might be the problem.   This is why there is such interest in NIS (sodium-iodide symporter) gene transfection, a gene-therapy modality that has been introduced in many types of cancers, such as prostate cancer and breast cancer.   There is a lot of interest in NIS induction because it has demonstrated a high potential for the treatment of non-thyroidal cancers.  Indeed, the whole purpose of the current interest in the NIS is because attaching anything to iodine can get your drug of interest into cells of interest.  Is there competition going on between fluorine and iodine for the NIS within cells?   I don’t know much about how much fluorine is normally in the body, but I did do several tests on myself, using a couple different testing mechanisms, and got results of “undetectable levels”.  This testing was done about 20 months post floxing however, not during the acute phase of my reaction.

Since being floxed, I’ve had plenty of heart palps, arrhythmias, and tachycardias.  It never crossed my mind to take Amiodarone for it.  All I had to do was take 5-10 ug Lugol’s iodine to relieve me of any heart arrhythmias for about 12 hours or so.  And during my “iodine trial”, after the first few days, I no longer experienced any heart arrhythmias.  Iodine itself worked for me.  This, by the way, was one difference between iodine and T3 for me: iodine was great for my heart arrhythmias while it was in my system, but T3 could exacerbate them, in particular, the tachyarrythmias, if I took too much.  The problem with iodine for me was that once the iodine wore off, I would experience heart palps again, and if you’ve read most of this document, you’ll understand all the issues I had with taking iodine.  So in my case, it wasn’t a simple case of “just take more iodine for my heart”, and I am NOT recommending anyone do this as a solution to heart problems.  I could have easily taken beta blockers to help with my “heart problem”.  However, I felt my heart arrhythmias were in fact secondary to some kind of TH/Iodine homeostasis problem, and I didn’t want to block or mask any effects of that while I was trying to sort all this out.  Additionally, I also developed increased heart poundings, palps, tachycardia, and arrhythmias when I was “too low” on TH also; presumably this was a compensatory response to “running out of Iodine/TH”.  I worried about how I would feel (even more fatigued) and if I would develop severely low blood pressure or possibly have a heart attack if this compensatory response were prevented. All my symptoms, and in particular my cardiac ones, were very “TH/Iodine responsive”, fluctuating up and down with my TH/Iodine status, so treating this “moving target” with beta blockers didn’t seem like a wise idea to me.

My point in bringing these examples up, is that iodine, the natural element that virtually all life forms evolved with and need to survive, may be doing much more than simply acting as “carrier molecules” or as a needed element “for the thyroid gland”.  I suspect there’s a lot more going on with iodine than researchers or practitioners realize yet.  It’s a shame that more researchers aren’t studying iodine alone, and the positive benefits of it.  And it’s a shame that iodine is what always gets the bad rap for any thyroid problems, when it may not be that at all.

A simple test I recommend all flox victims do is a spot urine iodine test.  It would be great to track this over time, to try and determine what role iodine status, if any, is playing in floxing syndromes.  It would not surprise me if low iodine turns out to be a susceptibility factor for FQT.  Since most people have no idea of their iodine status prior to being floxed, we’ll never know unless a controlled study would be undertaken specifically targeting this parameter. Still, monitoring post flox values over time may be enlightening.  It would also be interesting if people taking larger amounts of supplemental iodine (in the milligram range) to continuously monitor urine iodine excretion.  With Amiodarone Toxicity, urine iodine levels can take 6-18 months to return to traditional standardized levels.  Would the same be true of someone who has taken comparable milligram amounts of Iodine supplementation?  If not, why not?  I suspect it may be the iodine bound to the other components of Amiodarone and locked in tissues, that may actually be the problem here (if so, something to think about with FQ’s as well).  I suspect Iodine excretion levels might return to baseline quite quickly when large amounts of supplemental iodine alone are stopped.


A little bit about Amiodarone Toxicity that I’ve taken from the existing literature:

Symptoms of Amiodarone Induced Hyperthyroidism are similar to hyperthyroidism symptoms in general:  weight loss, heat intolerance or increased sweating, profound muscle weakness, unexplained fatigue, emotional lability, frequent stools, light or no periods for women, anxiety, nervousness, heart palpitations, tachycardia, tremor, goiter, and in extreme cases, A-fib, heart failure, psychosis, hallucinations, and mania.

Symptoms of Amiodarone Induced Hypothyroidism are similar to hypothyroidism symptoms in general:  fatigue, lethargy, cold intolerance, mental sluggishness, weakness, constipation, heavy or abnormal periods for women, dry skin, eyes and hair, goiter, and in extreme cases, myxedema coma.

A family history of certain conditions can also be important, including autoimmune disease, thyroid disease, medication history (including FQ’s, my opinion), and coming from an iodine-deficient area or having an iodine deficient history.

According to the scientific and medical literature, Amiodarone Induced Toxicosis -hyperthyroidim presents a therapeutic challenge because optimal treatments are limited due to the lack of randomized, controlled trials.  Sometimes stopping the Amiodardone is all that is needed, and everything will go back to normal after that.   But even if Amiodarone therapy is stopped, thyrotoxicosis can persist for up to 8-9 months because of the drug’s long half-life, and discontinuation of the drug often has no immediate benefit (urine iodine levels often take 6-18 months to return back to traditional standardized baseline).   Unfortunately, no randomized, controlled trials exist that determine the effect of stopping Amiodarone therapy in patients with AIT anyway, as apparently most clinicians prefer to continue using the Amiodarone and deal with these common adverse effects.   More often, additional treatments are needed, and these include the usual thionamides (methimizole, propylthiouracil), which block hormone synthesis by blocking iodine organification and the coupling of iodotyrosines, potassium perchlorate during the acute phase, which may block iodide uptake by the thyroid and deplete intrathyroidal iodine stores, and a relatively long course of steroids, which in addition to their anti-inflammatory effects, reduce conversion of T4 to T3 by inhibiting type 1 5′-deiodinase activity.   Regardless of the chosen medical regimen, the toxic state invariably takes several weeks to control because of the large stores of preformed intrathyroidal hormones.  Beta blockers, plasmapheresis, lithium, thyroid ablation and thyroidectomy have all been tried as well, with varying rates of limited success.

Amiodarone Induced Toxicosis – Hypothyroidism in patients with no preexisting thyroid disease often resolves after discontinuation of Amiodarone therapy. However, hypothyroidism may persist after discontinuation of treatment in patients with underlying chronic autoimmune thyroiditis and high titers of anti-TPO antibodies. In this case, the patient may require permanent T4 replacement therapy.  Amiodarone therapy is usually continued while T4 is used to normalize the TSH level.  In view of the often-severe underlying cardiac disease, consider maintaining the serum TSH concentration in the upper half of the reference range.  Levothyroxine is the drug of choice because it is not associated with the spikes in serum thyroid hormone concentrations observed in patients given L-T3, which also requires multiple daily doses. However, if Amiodarone therapy is continued, larger doses of T4 are required to offset the inhibitory effects of Amiodarone on the conversion of T4 to T3.


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