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Thyroid Hormone, Thyroid Hormone Metabolites And Mast Cells: A Less Explored Issue

redsun

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Self explanatory title. But basically describes relationships between thyroid hormones (T4 and T3), thyroid metabolites, and mast cell function as well as histamine.

Thyroid Hormone, Thyroid Hormone Metabolites and Mast Cells: A Less Explored Issue

"Interestingly, brain mast cells contain not only 50% of the brain histamine but also hormones, proteases and lipids or amine mediators; and cell degranulation may be triggered by different stimuli activating membrane bound receptors including the four types of histaminergic receptors. Among hormones, mast cells can store thyroid hormone (T3) and express membrane-bound thyroid stimulating hormone receptors (TSHRs), thus suggesting from one side that thyroid function may affect mast cells function, from the other that mast cell degranulation may impact on thyroid function. In this respect, the research on hormones in mast cells is scarce."

"Histamine levels were found high during the embryonic brain development (Pearce and Schanberg, 1969) and Sabria et al. (1987) reported T3 as possible candidate for controlling brain mast cells number and, consequently, the levels of brain histamine during development. Till now there is no evidence that brain mast cells may contain T3 but there are evidence that T3 metabolites activate the histaminergic system in the brain as well as in periphery (Laurino et al., 2018a,b)."

"Brain histamine (neuronal and not neuronal) is part of the mediators involved in the control of hypothalamic governed behaviors and it is also endowed of neuroprotective effects against excitotoxic damage (Kukko-Lukjanov et al., 2006). Furthermore, brain histamine is also part of the mechanisms of the neuroprotection offered by T3 metabolites (Cao et al., 2009; Laurino et al., 2018a,b). On the other hand, it is well assessed that histamine also controls the release of TSH (Roberts and Calcutt, 1983), a finding potentially linking the histaminergic system to the control of thyroid function. Actually, data regarding the effect of some histaminergic type 2 receptor antagonists on patient T3 serum levels seem to support, at least in part, the role of histamine in the control of TSH (Pasquali et al., 1981; Corinaldesi et al., 1987), thus suggesting a possible role of histamine in thyroxine regulation."

"Upadhyaya et al. (1993) demonstrated that in L-thyroxine-treated rats, histamine levels were found increased in the hypothalamus, thalamus and cortex of the rats, and that there was a positive correlation between circulating T3 and T4 levels and histamine. Csaba and Pállinger (2009a) demonstrated that very low histamine concentrations, not active on pain and inflammation, increased T3 mast cell content."

"T1AM is a multi-target compound (Bräunig et al., 2018) able to interact at G-protein coupled receptors, including the trace amine associated receptors, and also ion channels but not with T3 receptors. However, if we accept the trace amine associated receptors, the affinity of T1AM for such targets is much lower than its in vivo potency, thus making unlikely the participation of such targets in T1AM in vivo effects. Notwithstanding this, all the behavioral effects of T1AM (and of TA1) including the pro-learning effect, hyperalgesia and the neuroprotection were abolished by anti-histaminergic drug treatment of mice including type 1 receptor antagonists, a strategy which however does not allow to recognize the source of histamine which consists of neuronal and mast cell derived histamine. Considering T3 metabolites can pass the BBB reproducing most of the effects described for histamine, the timing of their effects, the localization of brain mast cells at the BBB, the possibility that mast cells, other than histaminergic neurons, are among the targets of T3 metabolites become a plausible hypothesis. "

"In fact, T3 supplementation is one among the cause of systemic itch (Reamy et al., 2011) and pruritus is one among the clinical symptoms of hyperthyroidism (Ward and Bernhard, 2005). Similarly, T3 metabolites induce itch (Laurino et al., 2015a,b) activating, histamine-dependent, pERK in the dorsal root ganglia. This pathway is considered selective for mast cell-derived histamine-induced itch sensation (Dong and Dong, 2018; Huang et al., 2018). Even if the definitive proof is lacking, T3 metabolites, by activating mast cells, might be the mediators of T3-induced itch. Furthermore, confirming that itch and pain sensation have some common neuronal pathways, T1AM and TA1 also induce histamine-dependent hyperalgesia to thermal stimuli (Manni et al., 2013), a condition typically activating mast cells (Zhang et al., 2012)."
 

Elize

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Gosh. Thanks sooooo much. High intake of T3 increase my experience with rashes and high histamine levels. I reduced my T3 by taking a 1/4 of my 5 mcg T3 by Mylan per day. Brain fog is improving and feel better. I tried using 10 mcg T3 but it didn't work out for me. I am on 75 mcg Synthroid. Tried Tirosint-Sol but the glycerol is a Histamine liberator and activate Mast Cells. Had to switch back to Synthroid.
 

redsun

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Gosh. Thanks sooooo much. High intake of T3 increase my experience with rashes and high histamine levels. I reduced my T3 by taking a 1/4 of my 5 mcg T3 by Mylan per day. Brain fog is improving and feel better. I tried using 10 mcg T3 but it didn't work out for me. I am on 75 mcg Synthroid. Tried Tirosint-Sol but the glycerol is a Histamine liberator and activate Mast Cells. Had to switch back to Synthroid.

Glad it helped make things more clear for you Elize.

Usually high histamine types would not benefit from thyroid meds, at least not initially. Thyroid of course is therapeutic in many ways but it would not remedy excess histamine levels and as you experienced, can worsen the effects of excess histamine. If you want to tone down histamine a bit (not too much but more manageable), high copper and vitamin C foods as well as some B6 (supplement small amounts of P5P, say 5mg) for a short while will help lower histamine levels.

Don't overdue it though you may end up with the opposite problem eventually, just try to be intuitive about it. But it would take a pretty long time to do that anyways.
 

Vileplume

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Thank you @redsun for referring me to this post. If I understand the above correctly, would this imply that hyperthyroidism could lead to excess histamine?

My main histamine symptoms are hot flashes, blood sugar dysregulation, brain fog, mood changes, and frequent breathlessness. However, I had these issues in the months before supplementing thyroid. And since supplementing thyroid, I don't always have these issues -- they get worse and better for days at a time, despite a consistent thyroid dosage. Further, my morning anxiety attacks have improved with thyroid supplementation.

Is it possible that thyroid improves certain symptoms and simultaneously increases histamine in the body?

*EDIT* just took a closer look at post #3 in this thread. That is IS possible for thyroid supplementation to solve certain problems, but worsen histamine. Super interesting. Any additional recommendations besides the copper, vitamin C, and B6? Do you think magnesium could also be beneficial?

Thank you.
 

redsun

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Thank you @redsun for referring me to this post. If I understand the above correctly, would this imply that hyperthyroidism could lead to excess histamine?

My main histamine symptoms are hot flashes, blood sugar dysregulation, brain fog, mood changes, and frequent breathlessness. However, I had these issues in the months before supplementing thyroid. And since supplementing thyroid, I don't always have these issues -- they get worse and better for days at a time, despite a consistent thyroid dosage. Further, my morning anxiety attacks have improved with thyroid supplementation.

Is it possible that thyroid improves certain symptoms and simultaneously increases histamine in the body?

*EDIT* just took a closer look at post #3 in this thread. That is IS possible for thyroid supplementation to solve certain problems, but worsen histamine. Super interesting. Any additional recommendations besides the copper, vitamin C, and B6? Do you think magnesium could also be beneficial?

Thank you.

Hyperthyroidism, because of the high stress hormone activity usually will control histamine to a degree. Adrenaline via beta 2 receptors inhibits histamine release from mast cells for example, and you will have sensitive adrenaline in hyperthyroidism. Cortisol will also be higher which suppresses immune activity (including histamine).

I dont think however most of your symptoms point to excess histamine. Excess of histamine which the body cannot keep under control will manifest as allergies, increased tears and mucus, heat intolerance (chronic, not just temporary), insomnia. So I think its likely something else.

Usually if you are getting breathlessness especially with thyroid it could be an oxygen delivery or utilization problem. Thyroid tends to improve anemias or oxygen use but not always and thus taking thyroid (which increases oxygen consumption) can make the problem worse or at least no improve it. Supplementing B-vitamins and vitamin A may help as you may have increased requirements due to the thyroid.

From a quick look your symptoms could be manifestations of drops in blood sugar. Hot flashes are supposedly caused by a drop in estrogen levels.
 

Vileplume

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Hyperthyroidism, because of the high stress hormone activity usually will control histamine to a degree. Adrenaline via beta 2 receptors inhibits histamine release from mast cells for example, and you will have sensitive adrenaline in hyperthyroidism. Cortisol will also be higher which suppresses immune activity (including histamine).

I dont think however most of your symptoms point to excess histamine. Excess of histamine which the body cannot keep under control will manifest as allergies, increased tears and mucus, heat intolerance (chronic, not just temporary), insomnia. So I think its likely something else.

Usually if you are getting breathlessness especially with thyroid it could be an oxygen delivery or utilization problem. Thyroid tends to improve anemias or oxygen use but not always and thus taking thyroid (which increases oxygen consumption) can make the problem worse or at least no improve it. Supplementing B-vitamins and vitamin A may help as you may have increased requirements due to the thyroid.

From a quick look your symptoms could be manifestations of drops in blood sugar. Hot flashes are supposedly caused by a drop in estrogen levels.
Thank you. The oxygen utilization problems and blood sugar dysregulation would go hand in hand, I imagine. I'll focus on the B's and A and see how that goes.
 

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