It Felt Like a Homeostasis Problem

One of the things that many people with “chronic, invisible, mystery illnesses”, including flox victims, often have in common is the extremely high sensitivity to almost everything:  drugs, supplements, foods, and environmental triggers that make one feel as if one is walking on a tightrope.  Life becomes a daily and moment by moment balancing act, trying not to incite setbacks or catastrophic “meltdowns” or decompensations with unknown triggers.  As my symptoms progressed over time, the same became true of me.

For a while, I was at my best while on a therapeutic suppressive dose of TH.  I started riding my bike, walking up to a couple of miles, swimming, and generally felt pretty hopeful overall.  I was much less sensitive, and the “tightrope” expanded to a “sidewalk” that provided some relief from the fear of total decompensation.  And yet, I still wasn’t “normal”.  Even while on a stable dose of TH, symptoms would still fluctuate.  Worse, symptoms fluctuated with every dose of T4 and T3 I took.  For example, when I would take T3, within an hour specific symptoms would start which I would then call my “hyper” or “hi” symptoms (because serum T3 was highest then).  After about 4-5 hours, the T3 would start metabolizing off (half life of T3 = 4-6 hours in general).  While that was happening I would go through another specific set of symptoms, which I would call my “hypo” or “low” symptoms.  In between, presumably when my cells were utilizing T3, I would be in “the sweet spot”, which was the time period I felt best.  Because of the short half life of T3, many thyroid patients who try T3 feel this “T3 wobble”, so I am not alone with this particular phenomenon.  However, in my case, I even felt this with T4, in particular within the first few hours of taking my daily dose.  Despite the much longer half life and lower metabolic activity of T4, I would still feel specific “hyper” or “hi” symptoms for a few hours after taking T4, and “hypo” or “low” symptoms before my next dose.  Most people don’t feel a “T4 wobble” like this.  I tried a twice a day dosing, with the same result.

This occurred not only with thyroid medication, but with other hormones, some supplements and meds, and even foods I ate.  Consequently, my entire day was spent feeling these internal fluctuations going on as I spread out my meds, supplements, and meals.  At best, it was incredibly annoying.  At worst, losing this “homeostasis” or “falling off the tightrope”, which could occur with frightening ease and rapidity, could mean weeks of misery trying to regain some kind of balance.  I grew to know these symptoms quite well, because they were being “caused” by me and were not random occurrences.  My post flox life revolved around attempting to “manually adjust” a system that had functioned on automatic without me ever feeling it for the first fifty years of my life.

When it came to serum TH levels, I was always within the normal lab ranges, even while not on thyroid hormone medication.  Additionally, the negative feedback system of my axis appeared to be working quite well, as confirmed with serial monitoring of serum lab values every 2-4 weeks.  Therefore, it appeared my “homeostasis problem” lay elsewhere.  I have seen hypotheses proposed that this homeostasis abnormality lies centrally, within the brain.  Certainly, this could be the case.  However, for a variety of reasons, I came to believe my homeostasis issues occurred peripherally, at the receptor and intracellular level, versus centrally, in the CNS.  This includes peripherally located receptors and transporters within the CNS or brain itself as well.

Of course, I don’t know what was really happening within me.  But I can tell you what it felt like.  It felt like there were no “doors” or “gates” on my cells, or like the “gates” were wide open on my cells.  When I would take any of the steroid or TH hormones, as well as iodine, it felt like “waves” were flooding my cells, just rushing in.  And right on time, usually at the first half-life, the “waves” would recede; either due to metabolism or leaving the cell again.  It felt like there was no blunting, or buffering, of effect; no “controlled” entrance to my cells.  For the hormones, this made me wonder if there was perhaps a problem with binding proteins, as these exist as a form of homeostasis, safely carrying hormones around in circulation until they’re needed.  But it also occurred with straight up iodine, selenium, and a few other non-hormonal substances.  This is one reason it felt like a peripheral receptor, cell transporter, cell signaling/signal transduction, or enzyme problem to me, as opposed to a central homeostasis problem.  And again, I was the one controlling the dosage amount and timing of these substances with exogenous meds; the actual hormonal dosages or “pulses” occurring in me were not due to signals initiated in the brain.

This phenomenon occurred not only with orally ingested medications, supplements, and foods, but also with sublingual and topical substances as well.  This was another reason it felt like a peripheral receptor/transporter, cell signaling, signal transduction, or enzyme problem to me.  Because it also happened with sublingual and in particular, topical medications, I did not believe my problem was from a “leaky gut”.  I did suspect, however, that the receptors/transporters and/or hormones and enzymes that are located or act systemically, including within the digestive system, were very affected as well.  When I would eat foods and feel symptoms develop both immediately and over time, I never thought of this as due to “leaky gut”, but instead thought of the individual minerals, aromatic or branched chain amino acids, or hormones hitting their individual receptors or transporters throughout my body, including the gut.

This phenomenon occurred with endogenous hormonal surges as well.  Because of this peripheral cell receptor/transporter, cell signaling/signal transduction, or enzyme problem, I felt exaggerated responses of any endogenous hormonal surges.  Note that there is a difference between saying something like “Excess hormonal surges are occurring and my body is spitting out “too much hormone”, versus “The receptors to certain hormones are disrupted or hypersensitive, and so normal hormonal surges now feel exaggerated due to these receptor malfunctions”.  Either or both of these situations could have been occurring in me.  Excessive hormonal surges of TH/T3 definitely occurred during thyroid gland flares, but I also felt the regular diurnal rhythm of the pulsitile surges which occurred throughout the day, and were most noticeable in the evening and throughout the night.  When it came to my own personal diurnal or circadian rhythm, I was extremely regular and predictable; it was obvious there was no problem there.  Prior to being floxed, I rarely felt any evidence of this internal turmoil, but with my exaggerated sensitivity to all hormones, I felt every increase in TH/T3, no matter how slight, and whether it was exogenously or endogenously produced.

Regarding the CNS symptoms, many of the receptors and transporters located throughout the body are also located within the brain, so in this way, these would be considered “peripherally located”, even though they’re in the brain.  However, I also considered there could be a breach or disturbance in the blood brain barrier instead of or in addition to a cell receptor, transporter, signal transduction, or enzymatic problem.

I didn’t have this homeostasis problem before being floxed.  And at least some of these homeostasis problems appeared to be directly related to TH/Iodine pathology, both within the thyroid gland and peripherally with TH targeted cells.  However, I think the Myasthenia Gravis/Acetylcholine and eventually glutamate related pathologies I had also contributed to this homeostasis problem.   Damaged or depleted mitochondria could also contribute to this.   Possibly the interplay between all these could easily be another reason I was unable to symptomatically regulate well even while on TH.  The food sensitivities increased dramatically after a massive Dec 2012 flare I experienced, and I think that’s when the “glutamate toxicity” started in earnest.  Each of these systems could have been attempting to compensate for the other, not to mention all the other hormonal and neuro-hormonal compensations going on.  My neurological symptoms increased substantially when there was a rapid rise in T3 or iodine.  There is a correlation between Myasthenia Gravis (MG) and Hyperthyroidism, and it was as if this T3/Iodine induced “hyperthyroid state” in me exacerbated the “MG-like” symptoms in me as well.

Another consideration for contributing or causing my homeostasis problem could be the anti-thyroid antibodies I had, or a “natural autoantibody problem”.  Natural autoantibodies are hypothesized to play a role in homeostasis (1, 2, 3, 4).  I experienced both thyroid and thymus gland symptoms in my later years post flox, I had all the anti-thyroid antibodies in moderate amounts, and my sensitivities continued to increase over time.   This certainly suggests a problem with the immune system playing a role in my homeostasis problems.

Yet another consideration for homeostasis problems might be what could be described as “leaky cell membranes” or “leaky lipid-bilayer membranes” (which also surround the nucleus and other organelles within the cell, as well as the entire cell).   Abnormal membrane receptors or transporters could contribute to this “leaky-ness”, but there might also be the possibility of compromised cell membranes directly, affecting permeability.  As one example, phospholipids, sphingolipids, and cholesterol are major components of cell and lipid-bilayer membranes.  In the paper entitled Metabolic features of chronic fatigue syndrome, research discovered that specific phospholipids, sphingolipids, and cholesterol are decreased in those suffering from ME/CFS, enough that these decreases may have the potential to be used as objective chemical signatures for a diagnosis of ME/CFS.  As the years went on, and my sensitivities continued to increase, it became apparent I met all the subjective criteria for a diagnosis of ME/CFS.  I don’t know if decreased measurements of some of these sphingolipids, phospholipids, and cholesterol in this study could contribute to compromised membrane integrity. But as I said before, it felt like there were no “doors” or “gates” on my cells, or like the “gates” were wide open on my cells; as if substances were simply “rushing in” or “rushing out”.  In some ways, this was most apparent with my CNS symptoms, feeling like it was a free for all with fluids, hormones, amino acids, minerals, and everything else affecting my brain sometimes.  Certainly, if membrane composition was compromised due to less availability of these lipids and cholesterol, this could be another possible mechanism for my “homeostasis” problems.


For those of you interested in learning or reviewing the basics of Cell Communication and Signaling, and how it contributes to cellular homeostasis, I found the following YouTube lectures.   When I say “It Felt Like a Homeostasis Problem”, this is what I mean about the “homeostasis” occurring a the peripheral cellular level.  Many pharmaceutical drugs target the receptors, transporters, enzymatic, and signal transduction mechanisms of cells.  “Serum homeostasis” — the level of thyroid hormones in my blood, for example, is not equivalent to “cellular homeostasis” — the amount and activity of the thyroid hormones within each cell.  So having “normal blood levels” of thyroid hormone, doesn’t guarantee that everything is working “normally” within my cells when it comes to utilizing thyroid hormones — especially if one or more of these mechanisms is disrupted.   From a symptoms standpoint, it felt like the symptoms were either “on” or “off”; I was either “too high” or “too low”, and my body’s response to any changes in hormones (or other substances) always felt “behind” in adjusting.   My cells could no longer regulate properly or maintain homeostasis.   Ultimately, what this really meant was that the slightest changes in hormone dosages or iodine had the potential to create severe symptoms in me.  Whereas prior to being floxed my cells automatically adjusted for changes in serum levels, now, I was trying to “manually adjust” the amount of serum hormone levels and other substances by regulating what I ate when, and how much and how often I dosed the hormones.

I am in no way affiliated with the person who made these, but I thank them for providing a very nice review of this topic.   There are also plenty of other videos on the same topics available for learning as well.    Part 1:  Cell Signaling Basics  Part 2:  G-Protein Coupled Receptors  Part 3:  Receptor Tyrosine Kinases.  I ask the question if FQ’s can act as Tyrosine Kinase Inhibitors in addition to Topoisomerase Inhibitors here.  Part 4:  Ion Channel Receptors   Signal Transduction

Membranes and Selective Permeability   YouTube video on how the phospholipid bilayer and transport proteins work together in a membrane to contribute to selective permeability


Discussion of nuclear receptors on Wiki:   Nuclear Receptors.    Ligands that bind to and activate nuclear receptors include lipophilic substances such as endogenous hormones, Vitamins A and D, and xenobiotic endocrine disruptors (such as FQ’s?).








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