If a person takes exogenous Substance X while limiting most or all other variables, and experiences repeated specific symptoms within minutes, hours, or days of taking substance X, it can be reasonably assumed that there is a correlation between Substance X and the experienced symptoms. There would also be a high suspicion that Substance X actually caused the experienced symptoms.
If such a person then experiences the same symptoms in the absence of knowingly taking exogenous Substance X, there could be a reasonable suspicion that somehow, someway, Substance X exposure had occurred. For example, perhaps Substance X was an ingredient in a new food that the person, unaware of this, ingested. In this case, based on the symptoms, the person might review all new foods and find that once again, exposure to Substance X had indeed occurred. This happened to me with iodine on a couple of occasions. Based on symptoms alone, I realized I was taking in increased micrograms of iodine, and went looking for the cause. One time was because I had changed multivitamins, and the new brand had 25 ug iodine in it. Another time was when I unknowingly ate a new brand of beans with extremely high iodine content due to a natural additive.
If a person experiences all of the symptoms of Substance X without exogenous exposure to Substance X directly, there could be a reasonable suspicion that somehow, someway, Substance X exposure had occurred in another form, perhaps endogenously. This is what may potentially have happened to me when I took Ciprofloxacin. In my case, my acute “flox reaction” felt very much like a thyrotoxicosis reaction. And this thyrotoxicosis reaction felt like one or more of the following:
- An extreme reaction mimicking a Hyperthyroidism state,
- An extreme reaction mimicking BOTH Hyperthyroidism and Hypothyroidism, at the same time,
- And/or an “Iodine Toxicosis” reaction, mimicking the above Hyper or Hyper/Hypo reaction.
My hypothesis of what happened to me during the acute phase of my reaction included this thyrotoxicosis reaction consisting of rapid and dramatic increases in serum and/or cellular T3 and T4, resulting in either an absolute or relative hyperthyroid state. Another possibility was that this acute thyrotoxicosis reaction consisted of rapid and dramatic increases in serum and/or cellular T3 and Iodine, with concomitant decreases in serum and/or cellular T4. My reaction “peaked” about 3-6 weeks post antibiotic, which is characteristic of and most likely represents the half life of T4. Unfortunately, I did not have a full thyroid panel done, with antibodies, or test iodine during the acute phase of my reaction. I did have a few TSH’s done – and they were swinging in and out of range, indicating something was going on with my thyroid though.
Most people understand that hyperthyroidism means “too much TH”. This is often diagnosed with increased levels of serum T4 and T3 above the normal laboratory ranges given for thyroid hormone. However, TH and Iodine physiology and metabolism are incredibly complicated. The negative feedback system for the thyroid and other steroid hormones is only a crude, first level approach to achieving serum homeostasis. Serum homeostasis is not equivalent to cellular homeostasis; it simply provides the stable pool of substrates for cells to draw from. As researchers are finding out and studying, there are innumerable mechanisms which exist to regulate localized intracellular levels of TH/Iodine via cell membrane and nuclear receptors, enzymatic processes, cell signaling, etc. often specific to tissue type. It would have been nice to see what my total and free serumT4/T3’s and iodine were doing during the acute phase with serial monitoring, in an effort to determine if what I was experiencing was an absolute change. However, I suspect there are any number of conditions that could result in a person essentially experiencing hyperthyroid symptoms despite normalized serum values. This is what I mean by a “relative or functional hyperthyroidism”, vs. “absolute hyperthyroidism”, which is defined more in the traditional sense of elevated serum T4 and T3 values. In my particular case, it might have been that my normal serum levels of TH would have naturally hovered around the 40% mark of the normal lab ranges, or perhaps I was already somewhat “lower” on the way to becoming “hypo” with subclinical Hashi’s, with even lower serum values. A “thyrotoxic event” may have elevated this to the 80% mark of the normal lab ranges. This, then, would have been considered normal by all testing standards. But if I was experiencing a severe receptor sensitivity, as I suspect I was, a rapid and dramatic increase of TH from 40% to 80% could have easily accounted for my severe symptomatology. In the same way, there are probably any number of conditions that could result in a person essentially experiencing hypothyroidism despite normalized serum values (a “functional” hypothyroidism).
There is also a small, but growing familiarity by both patients and physicians alike with the combination of feeling both “hypo” and “hyper” at the same time regardless of serum lab values. The term “Hashitoxicosis” is used to describe this phenomenon, and there are a few fairly good descriptions of it on the internet (see the PDF Hashitoxicosis Discussions). Most people describe it as wild fluctuations swinging between “hyper” and “hypo”, and only in a few cases will this actually be reflected in their serum values at any point in time. An important point to remember is that a person can be BOTH “hypo” and “hyper” at the same time, due to the different half lives of T4, T3, and Iodine, as well as antibody status and activity, TH receptor sensitivity, and probably a host of other factors that are unknown as of yet. In general, I tend to think my original Cipro reaction included dramatic elevations of both T3 and T4. However, based on my experiences in the subsequent several years, I think there may also be a possibility of T4 decreasing during this reaction. This might occur, for example, if Cipro is actually binding up or otherwise negatively affecting T4 — but not T3. Keep in mind that most of T3 is made intracellularly from T4, so if the thyroid gland “explodes” and then shuts down production, no more T4 or T3 is occurring from the gland – but available T4 in the bloodstream is continuing to be a supply source for intracellular production of T3 for several weeks more. Or, there could be a dramatic compensatory increase in T3 as a result of lowered T4, or perhaps even a dramatic increase in T4 à T3 conversion if FQ’s are affecting selenoenzymes, for example. In my case, this “Hashitoxicosis state” of feeling both hyper and hypo best describes what I was experiencing symptom wise for much of my floxing ordeal when it came to the thyroid related symptoms.
As an aside, I did test for pheochromocytoma to rule this in/out as contributing to my issues. I was highly symptomatic when the test was done, and the test procedure was done appropriately, so I felt confident in the negative test result I received in ruling this out for myself. I mention this because I think some of the flaring symptoms I experienced could easily have been caused by a pheo. I also did numerous testing of the HPA axis to help rule that out as a contributing to these issues as well.
There really isn’t much information available on “Iodine toxicosis”. Probably the closest thing is Amiodarone toxicity which can cause both hyper and hypothyroidism. 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 Autoimmune Thyroiditis (See the section entitled “My Floxing Timeline” for a 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. I’d like to add here that 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 those with true 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. 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. 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.
When I first started looking for a connection between FQ’s and thyroid related abnormalities, there were virtually no research papers written on this connection. In fact, there were only 2 that I could find, and neither of them proved much of anything when it comes to FQ’s and endogenous TH. However, a new paper came out in 2013 actually studying the effects of Cipro on TSH, T4, and T3 in rats. Unfortunately, it is rather poorly written, but the studies were very interesting to me none the less, in particular, some of their findings. Their results with rats given Ciprofloxacin were in agreement with my own symptomatic experience of T4 and T3 elevations occurring during the acute phase of my reaction. They found dramatic increases in both T3 (up to 95% in some cases) and T4 (up to 220% in some cases) occurred in rats given Cipro. They also found that TSH did not change appreciably while this was occurring. I wish someone (not funded or otherwise influenced by pharma) would repeat these studies, and measure a variety of basic thyroid related parameters, such as TSH, TT3/TT4, fT3/fT4, TBG, Tg, TPO, TgAb, TSI, Cortisol, ACTH, CBG, Se, Zn, Iron, Cu, Ferritin, Mg and Iodine status (consider Fluoride status during acute phase as well). Given what happened to me, I really can’t recommend doing similar studies in people just to test this. However, millions of people are going to continue to take Cipro regardless, so it would be nice to see such measurements done in people as well. Such extensive basic testing might help further localize where the TH disruption is occurring, at least at a crude level. I would also like to see repeats of similar experiments with other endocrine systems (HPA, sex hormones, PTH, and insulin/glucose).
I suspect that patients with healthy and normally functioning thyroid glands or other endocrine systems, can probably withstand these dramatic changes in the hormonal axes that may be occurring while on the FQ drug. For patients who don’t react at all to these drugs, they probably never even feel the fluctuations, as their hormonal axes can automatically adjust rapidly. However, I suspect anyone with a potential underlying subclinical or “silent” endocrinopathy, may be “pushed over the edge” into experiencing transient, long term or even permanent damage and pathology by FQ’s. Recovery may therefore depend at least partly on the initial robustness of the hormonal axes.
For additional considerations on this topic, I explore these two hypotheses of FQ-Induced Thyroid Damage in “Thyroid Damage Due to Collagen/Connective Tissue Damage” and “TKI’s: An Existing Example of Chemotherapeutic Drug Induced Acute, Delayed, and Permanent Thyroid Problems. Can FQ’s Act as TKI’s?”