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

[helvella]

The connections between thyroid and histamine issues have often been reported by patients, but routinely ignored by medics. At best some suggestion to take an antihistamine and get on with it.

Although not easy to understand (and I don't pretend to get more than a flavour) - the mere existence of the paper is a positive sign.

Mini Review ARTICLE

Front. Cell. Neurosci., 29 March 2019 | doi.org/10.3389/fncel.2019....

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

Elisa Landucci1, Annunziatina Laurino2†, Lorenzo Cinci2, Manuela Gencarelli2 and Laura Raimondi2*

• 1Section of Pharmacology, Department of Health Sciences, University of Florence, Florence, Italy

• 2Section of Pharmacology, Department of Neurology, Psychology, Drug Sciences and Child Health, University of Florence, Florence, Italy

Mast cells are primary players in immune and inflammatory diseases. In the brain, mast cells are located at the brain side of the blood brain barrier (BBB) exerting a crucial role in protecting the brain from xenobiotic invasion. Furthermore, recent advances in neuroscience indicate mast cells may play an important role in glial cell-neuron communication through the release of mediators, including histamine. 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. Recent pharmacological evidence indicates the existence of a non-genomic portion of the thyroid secretion including thyroid hormone metabolites. Among which the 3,5 diiodothyronine (3,5-T2), 3-iodothyroanamine (T1AM) and 3-iodothyroacetic acid (TA1) are the most studied. All these compounds are endogenously occurring and found to be increased in inflammatory-based diseases involving mast cells. T1AM and TA1 induce, as T3, neuroprotective effects and itch but also hyperalgesia in rodents with a mechanism largely unknown but mediated by the release of histamine. Due to the rapid onset of their effectiveness they may trigger histamine release from a cell where it is “ready-to-be released,” i.e., mast cells. Following a very thin path which passes through old experimental and clinical evidence, at the light of novel acquisitions on endogenous T3 metabolites, we aim to stimulate the attention on the possibility that mast cell histamine may be the connector of a novel (neuro) endocrine pathway linking the thyroid with mast cells.

Full paper freely available here:

frontiersin.org/articles/10...

[linda96]

Fabulous.

I have two types of thyroid hormone deficiency, and an up to now a weird reaction to anti-histamine. When anti-histamine touches my skin the skin just splits open. It takes months for the split to heal properly, and decades later where the one split is, just a white mark and no skin colour. Mast cell problem, surely?

[Greekchick]

Thanks for posting this. It explains my continuing hives after TT. I will be checking this with my immunologist as I am scheduled to see him soon. Antihistamines are not for long term use in any case and can cause very unpleasant long term side effects.

[Batty1 in reply to Greekchick]

Greekchick, I have had hives off and on since my thyroidectomy 2.5yrs ago and I had them as a kid mainly my mouth and I thought I out grew them but recently I had to be rushed to Emergency Room I had burning skin and lumps on top of lumps in my head and on my neck. I was given steroids and antihistamines. When I mention hives and thyroidectomy to Dr. they say no!

[Greekchick in reply to Batty1]

They just don’t know. They also simply assume that after TT all sort of weird things will happen to you , and both my surgeon and endo told me that. I have had allergies since I was a kid and had asthma that stopped at the age of 12 - not returned since. But as I am getting older , I have more allergic reactions (prior to TT) to foods and other substances. I was stunned when my endo (who is really good - and who cares) thought the hives were just part of my body’s adjustment to the new hormonal reality of TT after Graves . I found another article on hives and Hashis post thyroidectomy that I will post the link to later. Good luck with your situation - sending you good thoughts! At least I am only getting one hive a day now and they are small - so I am hoping my body is adjusting and these will not be permanent.

[Greekchick in reply to Batty1]

Also forgot to mention I have Graves - so it happens regardless of condition.

[Hidden in reply to Batty1]

But if you have an autoimmune version of a thyroid problem (Graves in your case) surely that is evidence that your immune system isn't working properly. So you would expect such a patient to be more susceptible to allergies and related problems?

I'm not even a doctor but can see that!!!

PS, I have Hashis, but suffered from asthma as a child too

[Batty1 in reply to Hidden]

I don't and never had graves. I probably had or have Hashimotos disease although it was never addressed by Endo and I have autoimmune disease but I actually lost my thyroid to cancer.

[Hidden in reply to Batty1]

Sorry, someone else said they had Graves and I got mixed up. But, as I said, you would expect other immune system problems with any kind of autoimmune condition.

[Greekchick in reply to Hidden]

I would guess it depends on how severe your allergies are. Mine are to house dust primarily and ragweed, and have been kept largely kept under control for years because I had desensitization shots. But I agree with you - an overtuned immune system is likely to resurface and you don’t have to be a doc to see that!!

I think the issue with the hives for me was first - was I allergic to Synthroid - and once that possibility was ruled out , hives is not something seen often - we don’t have a lot of thyroïdectomies in Canada unless you have thyroid cancer, or like me, a goiter that grew huge in a month and had to come out. RAI is the preferred treatment here and is what is offered to most people.

The only good news is that now both my docs will recognize this and I have both of them the article I found and will give them helvella’s next time I see them. Wishing you good health!

[Hidden in reply to Greekchick]

You too x. Yes, the allergy thing is tricky. I had hay fever some time after growing out of the asthma but eventually that more or less disappeared too, thankfully. This year is the first time I've refused a flu jab. With not yet stabilised Hashi's it just seemed wise to risk getting flu rather than a reaction to the jab

[cazzaleo]

Thanks for posting! I’ve just started to research histamines as have started to get migraines every few days and hives unless I take antihistamines.

[Hidden in reply to cazzaleo]

Migraines are likely yet another symptom of thyroid problems. I find I have fewer migraines since the menopause, and fewer still if my Hashimoto's is more or less under control

[cazzaleo in reply to Hidden]

I agree but these particular very frequent ones do appear to be linked to a potential histamine as they’ve been occurring at the same time as the hives and both stop as long as I’m taking antihistamines every day

[Coconutty]

Interesting! I’m currently being tested for issues with histamine / DAO, hoping it’s the missing piece of the puzzle. The more I learn the less I know.

[WestBurrafirth]

I am certain there is a link between thyroid and histamine. I now take a daily antihistamine pill which keeps the hives (Urticaria) at bay. I am seeing an immunologist at some point but can't get an appointment until end of September!

[Aunds]

I was diagnosed with MCAD (Mast Cell Activation Disorder) three years ago. After repeated bladder infections I had a biopsy that showed 100 times the normal level of histamine in my body. I also have Hashimotos so I’m interested to read the connection, let’s hope there is more research into this field.

[TakeCareOfYourself]

I didn’t know there was any kind of connection! But since becoming hypothyroid I’ve noticed that my allergies are on the increase - horrid hay fever at the moment, for example, the first time I’ve had it in April rather than end of June, allergic to my cat, etc. .

[HLAB35]

It has already come up as an issue in my family. Being histamine aware with foods is really helpful. I recommend histamine blockers like Quercetin and Nettle. The problem with antihistamines is that they also block DAO production (the enzyme that breaks histamine down) so are not a long term solution.

Also, being zinc deficient allows more histamine to be released from cells.

[Auryn_Lieb]

I thought this was some really interesting information about the connection between a lesser known thyroid hormone metabolite known as T1AM and how it affects histamine regulation:

chronicfatiguediagnosis.com...

[bookish in reply to Auryn_Lieb]

Really interesting and helpful, thank you. Seem to be a lot of links between Dysautonomia and mast cells, and also both Small Fibre Neuropathy (which is apparently at the root of about half of fibromyalgia cases) and Sjogren's.

[Sixties123]

Hi this post is really interesting to me as I too had Graves and went through RAI , currently taking 100mcg Levothyroxine and 25mcg liothyronine . I started roughly 2 years and 3 months ago getting what looked like bites and were intensely itchy but they never really go away just more appear as some fade and the go say I have hives or urticaria . It’s driving me mad but recently I’ve been investigating the link between histamine and thyroid issues and wondered if there was a connection? Is there a way to test for this condition and how do I approach my Gp who I see on Wednesday this week ? Should I be asking to see an allergy specialist ? Get bloods done ? It’s so confusing and I’m living on Benadryl ! I live in the uk x thanks in advance

[helvella Administrator Thyroid UK in reply to Sixties123]

The trouble with these papers that raise questions and make observations is that no-one knows what can be done for real-world patients.

Might be worth asking for a referral.

Long-term antihistamine usage is not a good idea. But what else to do? Possibly try swapping round the various over-the-counter antihistamines so you are not always using the same active ingredient?

[Sixties123 in reply to helvella]

Thank you for that the Gp prescribes me certirizine every month so that’s goong to have to stop , is there a blood test to check the DAO levels ( the stuff that breaks down histamine I believe) ? Thanks

[helvella Administrator Thyroid UK in reply to Sixties123]

You might be better off taking antihistamines regularly than suffering - but it is so very easy to take them without having ever considered whether they have any other impact.

Yes, there is a DAO test. There are questions as to whether it is worth testing...