Low Thyroid, MCAS, and POTS / Dysautonomia

In case you missed the previous post, go back and read that now (or this probably won't make sense unless you've been in my world for a while). Here's how that functionally low T3 environment within the body creates the terrain for MCAS and POTS/dysautonomia to show up:

The Low-T3 & MCAS Connection

Active T3 regulates the rate of cellular metabolism, and this is how it's relevant in the gastrointestinal tract (where MCAS symptoms often start).

When T3 drops:

Gut motility slows down: Slow motility creates conditions suitable for the overgrowth of opportunistic bacteria in the small intestine bacterial overgrowth (SIBO).

Stomach acid drops: Most studies have found a direct relationship between healthy thyroid function (healthy levels of T3 within the cells) and healthy production of stomach acid. In these studies it was found that when T3 drops, stomach acid drops. This can do a few things…

• makes indigestion more likely

• results in the esophagus spasming or not opening well during meals (so you get this backed up feeling above the stomach)

• overall disrupts healthy digestion (sets the stage lower in the GI tract for SIBO, etc., etc.).

The gut lining: The cells lining the intestines turnover quickly. Thyroid hormone (specifically T3) influences how new intestinal cells are made, how they mature, and how well they perform jobs like absorbing nutrients and maintaining the gut barrier. Low T3 has been shown to disrupt this normal intestinal renewal and function. And here's where it gets particularly interesting for histamine intolerance:

DAO is made by mature cells lining the intestine.

(Yes, your body is able to make its own DAO enzyme. Which is why healthy people don’t have to pop DAO enzyme tablets before every meal.)

There’s not yet research I’ve found demonstrating that low T3 correlates with lower DAO, but knowing that T3 helps regulate the development and function of the very cells responsible for producing DAO makes that an awfully interesting question.

And thyroid may affect mast cells more directly: A 2022 animal study found that hypothyroidism (low thyroid):

• increased mast-cells by as much as 4.5-fold

• increased tissue histamine by up to 50%

• increased mast-cell degranulation

If this is the first time someone has connected low thyroid physiology, histamine clearance and mast-cell reactivity for you, this is exactly the physiology we work with inside Reclaim Wellness Intensive.

→ Discover more about the Intensive here.

The Low-T3 & Dysautonomia Connection: Blood Vessel Rigidity and Orthostatic Intolerance with or without POTS

Blood Vessels: T3 influences the ability of blood vessels to constrict and relax. It’s been repeatedly shown that low-thyroid states are associated with increased arterial stiffness and impaired endothelial (blood vessel lining) function.

If you're here for POTS/dysautonomia, this matters: maintaining blood flow to the brain when standing requires rapid (and coordinated) changes in blood vessel tone. Impaired vasoconstriction (blood vessels narrowing in diameter to maintain blood pressure when you stand up) and excessive lower-body blood pooling are well-documented in POTS, the heart rate increases to compensate for reduced blood flow/drop in blood pressure.

NOTE: You may also be someone who has a normal (or even low) heart rate and yet you struggle with “positional headaches” or getting dizzy on standing. Going from lying down to sitting or standing up can make that headache… um… untenable.

There’s a name for this. Orthostatic Intolerance without POTS. I more broadly call any struggle with blood pressure in different positions (lying down vs. sitting or standing) and/or trouble regulating body temperature, dysautonomia. It’s a broader umbrella term recognized by Western medicine.

Now, one more note here… just like low T3 and dysautonomia/POTS and MCAS are connected, so too is hyperthyroid (too much T3 and/or T4 hormone). This is a throw back to the Alice in Wonderland analogy from the last post. That said, there is growing evidence of a correlation between POTS and Hashimoto's thyroiditis (autoimmune low thyroid) and it seems low thyroid is more often discussed/connected with POTS (there's more to this that we'll unpack in future posts).

The Low-T3 & Cortisol Connection

The relationship between thyroid hormone and cortisol is a two-way street.

Cortisol and stress signaling can alter the hypothalamic-pituitary-thyroid (HPT) axis and thyroid hormone metabolism. And… thyroid hormone also affects cortisol levels in the body.

Thyroid hormone levels change how cortisol is produced, metabolized, and cleared from the body. In hypothyroidism, researchers have found substantially slower cortisol clearance and a longer cortisol half-life even when 24-hour cortisol production remained normal. Thyroid replacement allowed a shift back into healthy cortisol rhythm.

In other words, changing thyroid function can change cortisol function and vice versa.

If you’ve been going through the program, Follow the physiology: What drives MCAS (and POTS/dysautonomia)? you’ll see we’re right back where we started… with a conversation around cortisol. If you’re not in that program, here's the link to access it. Now back to the conversation.

Cortisol’s role in POTS, Orthostatic Intolerance without POTS, and dysautonomia

In case this is your first interaction with me, cortisol is not the demon it’s been made out to be. Cortisol is the body’s primary anti-inflammatory hormone and it’s absolutely essential for life itself (and for health).

Just as cortisol can be too high, it can also be too low. Even dysregulated cortisol rhythm has a profound impact on health (and plays a huge role in both POTS and MCAS).

When cortisol is low or dysregulated (especially chronically), it’s common (and I think moreso than anybody’s yet giving credit for) for the RAAS system (a hormone system that regulates blood pressure) and anti-diuretic hormone (vasopressin) to be thrown out of balance as well. If you struggle with POTS (or low blood pressure on standing without tachycardia), you probably just sat up straighter.

It’s also surprisingly common to have adrenaline surges with low/dysregulated cortisol as the body attempts to maintain blood pressure. In my mind, this is part of the reason for the temperature swings/hot flashes that show up for many people struggling with dysautonomia.

For MCAS, the adrenaline piece is also interesting because of adrenaline’s ability to act as a pro-inflammatory molecule. I’ve got several ideas about the link there, for now we’ll save that conversation for another time.

Again, if you haven't completed Follow the Physiology, you'll probably want to take a look at that full program... it goes deeper into the connection between cortisol rhythm and POTS/MCAS symptoms.

Now, if you’re here looking for the connection between low thyroid and MCAS or dysautonomia, you may be realizing the rabbit hole goes deeper than thyroid (or cortisol) alone. In my own healthy journey, I realized this. In fact, it wasn't until after I was at a physiologic replacement dose of thyroid hormone (I have Hashimoto's thyroiditis... autoimmune low thyroid) that I started experiencing mast cell activation/high histamine and orthostatic intolerance (for me it was without the rapid heart beat with positional changes so not quite POTS).

I'm someone who's figured out a ton about health and wellness (I single handedly broke free of urinary urgency/recurrent UTI symptoms and had figured out a lot of other symptoms on my own after Western medicine failed me) and I'm also someone who second guesses herself at every turn. So, when these symptoms popped up, I'd finally developed enough self-confidence to not throw the baby out with the bath water but instead to take one big step back and ask "What's really going on here?"

Ultimately, I realized this... you can't force the body to make more energy. It has down-regulated energy production for a reason (to keep from burning out). Sure, I was on a full physiologic dose of thyroid hormone. Sure, I'd overcome a laundry list of life altering symptoms. Now though? I was still in a symptom loop. Now, I was struggling with mast cell activation and dysautonomia/orthostatic intolerance.

That's when I realized, this was unsustainable.

Demanding more energy from a cell that's choking on its own metabolic waste doesn't work. But neither does simply slowing everything down and asking the body to get by on less and less energy.

It takes energy to clear waste. And, a body struggling to clear waste responds by throttling back energy production. It's the ultimate catch 22.

The body needs enough capacity to create energy and enough capacity to deal with the metabolic exhaust that's made when it's creating energy. You can't really separate the two.

Increase energy production without adequate clearance and you risk more inflammation, more reactivity, more symptoms. (This is why I was now struggling with mast cell activation and dysautonomia.)

Focus entirely on clearance without rebuilding energy production and you run into the same problem: clearing waste requires energy, too. (This was why I was reacting so intensely 3 days into protocols.)

For me, this realization changed everything.

Now, instead of asking How do I get more T3 into my cells? or How do I stop this histamine reaction? or How do I get my blood pressure to behave when I stand up?, I started asking:

What does my body need to have enough capacity to create energy and clear the waste at the same time?

I began to realize how important sequencing is when restoring depleted nutrients. I began realizing clearance goes way beyond Phase 1 and Phase 2 elimination. Ultimately, I developed a protocol. It's how I walked myself out of being highly reactive to everything. That protocol is now offered inside the Reclaim Wellness Intensive.

It's the protocol I wish I'd had from the start, before I spent years figuring out which nutrients to introduce, in what order, how to increase energy without overwhelming clearance, and how to build enough capacity to finally address the things draining it.

I built Reclaim Wellness Intensive so you don't have to spend years figuring all of that out the way I did.

→Take a look inside Reclaim Wellness Intensive

References

Sabatino L, Vassalle C, Del Seppia C, Iervasi G. Deiodinases and the Three Types of Thyroid Hormone Deiodination Reactions. Endocrinol Metab (Seoul). 2021;36(5):952-964. doi:10.3803/EnM.2021.1198. PMID: 34674502; PMCID: PMC8566136.
Snapshot: D1/D2/D3; T4→T3 activation; T4→rT3 inactivation; tissue-specific thyroid hormone metabolism.

Fliers E, Boelen A. An update on non-thyroidal illness syndrome. J Endocrinol Invest. 2021;44(8):1597-1607. doi:10.1007/s40618-020-01482-4. PMID: 33320308; PMCID: PMC8285315.
Snapshot. It supports tissue-specific deiodinase responses, hypothalamic D2↑/D3↓ during illness, hepatic D1↓, altered TRH/TSH regulation, and the existence of markedly low T3 without the expected increase in TSH.

Köhrle J. Thyroid hormone deiodination in target tissues—a regulatory role for the trace element selenium? Exp Clin Endocrinol. 1994;102(2):63-89. doi:10.1055/s-0029-1211267. PMID: 8056056.
Supports: tissue-specific activation/inactivation of thyroid hormone and nutritional/hormonal regulation of deiodinases.

Spaulding SW, Chopra IJ, Sherwin RS, Lyall SS. Effect of caloric restriction and dietary composition on serum T3 and reverse T3 in man. J Clin Endocrinol Metab. 1976;42(1):197-200. doi:10.1210/jcem-42-1-197. PMID: 1249190.
Snapshot: total fasting produced a 53% reduction in T3 and 58% increase in rT3. The study also found a major effect of dietary carbohydrate on T3.

Yaylali O, Kirac S, Yilmaz M, et al. Does hypothyroidism affect gastrointestinal motility? Gastroenterol Res Pract. 2009;2009:529802. doi:10.1155/2009/529802. PMID: 20224642; PMCID: PMC2833301.
Snapshot: hypothyroidism and impaired GI motility. In women with primary hypothyroidism, both esophageal transit and gastric emptying were significantly prolonged.

Sirakov M, Plateroti M. Thyroid hormone signaling in the intestinal stem cells and their niche. Cell Mol Life Sci. 2022. doi:10.1007/s00018-022-04503-y. PMID: 35947210; PMCID: PMC11072102.
Snapshot: T3/TRα1 signaling regulates intestinal epithelial stem-cell biology, proliferation, differentiation and homeostasis.

Maintz L, Novak N. Histamine intolerance—The more we know the less we know. A review. Nutrients. 2021. PMCID: PMC8308327.
Snapshot: endogenous DAO/AOC1 is produced in intestinal epithelial cells, particularly small-intestinal enterocytes, and functions as an enzymatic barrier to ingested/extracellular histamine.

Chieffi Baccari G, Falvo S, Lanni A, Di Fiore MM, Cioffi F, Santillo A. Mast Cell Population and Histamine Content in Hypothyroid Rat Tissues. Animals (Basel). 2022;12(14):1840. doi:10.3390/ani12141840. PMID: 35883387; PMCID: PMC9311769.
Snapshot: experimental hypothyroidism increased mast-cell numbers up to 4.5-fold, tissue histamine up to 50%, and increased the proportion of degranulating mast cells.

Brusseau V, Tauveron I, Bagheri R, et al. Heart rate variability in hypothyroid patients: A systematic review and meta-analysis. PLoS One. 2022;17(6):e0269277. doi:10.1371/journal.pone.0269277. PMCID: PMC9165841.
Snapshot: 17 studies/11,438 participants; hypothyroidism was associated with decreased HRV, lower parasympathetic-associated measures and increased sympathetic-associated measures. Autonomic alteration increased with hypothyroidism severity.

Parsaik AK, Singer W, Allison TG, et al. Orthostatic intolerance without postural tachycardia: how much dysautonomia? Clin Auton Res. 2013;23(4):181-188. doi:10.1007/s10286-013-0199-5. PMID: 23729158; PMCID: PMC3902804.
Snapshot. Mayo compared 100 patients with OI without tachycardia with 84 patients with POTS and found broadly similar clinical presentations aside from the excessive orthostatic HR response.

Meta-analysis on the Association Between Thyroid Hormone Disorders and Arterial Stiffness. Journal of the Endocrine Society. 2022. PMID: 35284772.
Snapshot: across 11 observational studies, aortic pulse-wave velocity was significantly higher in both subclinical and overt hypothyroidism than controls.

Gong N, Gao C, Chen X, Fang Y, Tian L. Endothelial Function in Patients with Subclinical Hypothyroidism: A Meta-Analysis. Horm Metab Res. 2019;51(11):691-702. doi:10.1055/a-1018-9564.
Supports: impaired endothelial function in subclinical hypothyroidism.

Impact of thyroid disorders on flow-mediated dilation: a systematic review and meta-analysis. 2025. PMID: 41313532.
Snapshot: 42 studies found significantly impaired flow-mediated dilation in untreated hypothyroidism, improvement following levothyroxine, and values similar to controls after euthyroidism was restored.

Dynamics of 24-hour endogenous cortisol secretion and clearance in primary hypothyroidism assessed before and after partial thyroid hormone replacement. J Clin Endocrinol Metab. 1990;70(1):155-161. doi:10.1210/jcem-70-1-155. PMID: 2294128.
Snapshot: Hypothyroid subjects had normal endogenous 24-hour cortisol production but a cortisol half-life of 155 vs 73 minutes in controls. Thyroid replacement reduced the half-life to 112 minutes.

Gereben B, Zavacki AM, Ribich S, Kim BW, Huang SA, Simonides WS, Zeöld A, Bianco AC. Cellular and molecular basis of deiodinase-regulated thyroid hormone signaling. Endocr Rev. 2008 Dec;29(7):898-938. doi: 10.1210/er.2008-0019. Epub 2008 Sep 24. PMID: 18815314; PMCID: PMC2647704.

Dubois A, Goldman JM. Gastric secretion and emptying in hypothyroidism. Dig Dis Sci. 1984 May;29(5):407-10. doi: 10.1007/BF01296214. PMID: 6714056.

St Germain DL, Galton VA, Hernandez A. Minireview: Defining the roles of the iodothyronine deiodinases: current concepts and challenges. Endocrinology. 2009 Mar;150(3):1097-107. doi: 10.1210/en.2008-1588. Epub 2009 Jan 29. PMID: 19179439; PMCID: PMC2654746.

Bakiri F, Benmiloud M. Fonction hypothalamo-hypophyso-surrénalienne au cours de l'hypothyroïdie primaire [Hypothalamic-pituitary-adrenal function in primary hypothyroidism]. Presse Med. 1994 Feb 19;23(7):320-4. French. PMID: 8208691.

Rodríguez-Gutiérrez R, González-Velázquez C, González-Saldívar G, Villarreal-Pérez JZ, González-González JG. Glucocorticoid functional reserve in full-spectrum intensity of primary hypothyroidism. Int J Endocrinol. 2014;2014:313519. doi: 10.1155/2014/313519. Epub 2014 Aug 7. PMID: 25180035; PMCID: PMC4142294.