Here, I’ll use my own personal example to discuss a few dimensions of T3 monotherapy, which I envision as a “wheelchair.”
I’m drawing on the fictional analogy I developed in an earlier post, where I imagined thyroid disease like crippling foot disease.
- The therapy of 100% T4 can be seen like a walking stick or cane.
- Next in complexity comes a walker, which represents a rolling, adjustable T3-T4 combo.
- When the first two options fail, which they do for some thyroid patients, the last resort for safe, effective treatment is 100% T3 medication, which is like a wheelchair.
Here I’m discussing long-term full thyroid replacement T3 monotherapy. This means that a person relies on T3 medication for for 100% of their thyroid hormone supply, usually without any measurable T4 in circulation. I’m not talking here about combining T3 with T4 or desiccated thyroid — that’s for another post.
I’d like to use my experience and scientific knowledge of T3 monotherapy to help other people understand why people like me need it, how we use it, what life is like, and how it functions uniquely as an adaptation that can be therapeutic.
My overall message is that T3 medication, like a wheelchair, needs a larger accommodation — you may need to change some architecture in your life, like ramps and door frames, based on the size and type of wheelchair.
In a similar way, T3 monotherapy, if necessary, needs a lifestyle accommodation, an attitude adjustment, as well as an understanding of its biochemical abnormalities.
Wheelchairs, a visible medical technology, are far more familiar to medicine than T3 monotherapy, a rather invisible one. If you ever have to go down this path, you will have to deal with all sorts of unscientific prejudices and fears about T3 hormone dosing and response that are a result of medical and pharmaceutical ignorance of the T3 therapeutic reality.
GENERAL INFO ABOUT T3 MEDICATION
In Canada, T3 medication is sold by Pfizer, and the brand name is Cytomel. The name of the T3 molecule in your body is triiodothyronine, but when people talk about the pharmaceutical, it is called “liothyronine sodium.”
The T3 liothyronine preparation is considered a regular “fast release” variety. That’s the standard T3 pill most people are talking about. (We also have access to slow release in Canada through “compounding pharmacies,” and they are dosed differently, usually once every 12 hours.)
Liothyronine sodium is classified as a “bioidentical” hormone, which means that even if it is synthetically produced from vegetable matter, our bodies treat the molecules like our own and can use them in the same way. Just like our own T3 molecules, these get bound to “carrier proteins” that help it circulate in our blood, and a small fraction of it becomes “Free” and available for transport into cells. T3 gradually gets converted or metabolized into two types of T2, then T1, and T0 by an unique interplay of three “deiodinases,” enzymes whose job is to de-iodine-ate or remove iodine atoms from its molecule. (Mugesh, n.d.) Other metabolic reactions occur as well, not just deiodination.
Therefore, this medication is not a foreign chemical, but a functional human hormone.
However, our bodies are not used to obtaining T3 in doses from a pill delivered through the GI tract, and our bodies are used to T3 in the context of T4, so there are some adjustments that are involved in T3 monotherapy.
Cytomel is almost completely absorbed through the GI tract, so it’s not as challenging to deal with the timing of the dose in relation to food or supplements compared to T4.
CAUTION: T3 therapy has to be handled with care because of its potency and the way it creates fluctuations in Free T3 levels in our blood that are related to the size of each dose. In particular, the product monograph for Canada’s Cytomel by Pfizer says this:
“Patients with uncorrected adrenal insufficiency, as thyroid hormones increase tissue demands for adrenocortical hormones and may thereby precipitate acute adrenal crisis.”
Increased heart rate at very small doses like 2.5 mcg can be caused by insufficient cortisol, according to many patients’ clinical experience. This degree of oversensitivity is a sign that something needs to be fixed. Sustained release T3 may also be gentler on such people.
Most people like me without cortisol problems can eventually tolerate larger doses of fast-release T3 without any jarring cardiovascular response. People who fear T3 in the context of heart pathologies do not usually consider recent cardiology studies showing the hormone does in fact play a “cardioprotective” role in the heart and performs many necessary functions. (von Hafe et al, 2019)
T3 is not exactly like a stimulant even though it does support your metabolic rate. (Small doses can help with intermittent insomnia caused by insufficient T3 and will put me back to sleep within an hour.) T3 works in different ways in different organs and tissues to turn both on and off genomic activity needed to perform essential functions all over your body. Yes, T3 can turn OFF genes that are in the “ON” state when the thyroid hormone receptor is not bound to a T3 hormone molecule. (Vella & Hollenberg, 2017)
This post is not meant to be a full introduction for users of the medication.
If you are considering it or beginning to learn how to use it, I recommend the product monograph for Canada’s Cytomel by Pfizer regarding drug interactions and safety precautions. I also provide resources by Paul Robinson in the reference list that I found helpful and practical.
MY UNIQUE EXAMPLE
I’ve lived my life in a T3 monotherapy “wheelchair” since Spring 2016, with the exception of an attempt to transition to a T3-T4 combination therapy in 2017 that unfortunately showed that was not a healthy option for me.
I’m not alone, by far. I’m part of some online communities of people on T3 monotherapy. I have read all the scientific publications I can find about people maintained on both short-term and long-term T3 monotherapy, and they are a treasure.
Each T3-only person comes to this mode of therapy either after a long road of suffering on the wrong thyroid therapy for their body, or an acute crisis, and it usually is a last resort.
It’s the most challenging form of thyroid therapy, but it works. It can be done safely with due caution and an individualized approach.
You can’t generalize about why each of us needs T3 alone. The unique combination of thyroid disease and metabolic disability is going to be different from person to person on T3 only.
I can generalize one thing about people on T3 monotherapy: By the time we get to this last resort, it is almost always the only thing or best thing that helped, and we will get sick again if we try to move back toward a combination of T4-T3 dosing.
When we realize we depend on T3, we are more than willing to commit to the responsibility it demands of us, and we’ll fight tooth and nail to keep it because by then, we usually know how important it is for our health.
HEALTH CRISIS — FINAL 3 MONTHS ON T4-MONOTHERAPY
When I fell into a health crisis, I had been “maintained” on T4 monotherapy (Synthroid, levothyroxine) since about 2003, about 13 years.
I had chronic low FT3 and high-normal FT4 for at least the final 3 years on standard Synthroid therapy, which is as far back as my thyroid test history records go.
My TSH on Synthroid was absolutely uncontrollable, unreasonable, and generally high due to a rare genetic condition I’ll mention below. Plus, I have an atrophied thyroid, now known to be caused by TSH-Receptor blocking antibodies, and these antibodies act directly on the pituitary and can make TSH fluctuate high in ways that contradict the FT4 level. My former doctors compromised by ignoring my wild TSH and just keeping my FT4 under the top of its reference.
Then something triggered a fall into illness in late 2015, and I was nearly incapacitated by multiple mysterious health challenges for three months, mid-January to mid April 2016.
During this challenging time of daily suffering, I acquired an adverse cardiovascular response to T4 hormone. The worst symptoms with T4 were night and day random chest pains that seemed to be spasms or painful squeezes in or near branches of my aorta. I kept a pain and symptom diary and the data was interesting to analyze. Within a few seconds after spasms, I would get numbness and weakness in the adjacent limb, or pain in the organ it led to, or lightheadedness as if from poor blood circulation if the vessel led upward to my neck and head.
This was not “chest wall pain.” No, I eventually developed a costochondritis flare-up of my Ankylosing Spondylitis in my lower ribs during this health crisis, but that was a very different sort of pain that responded to motion.
My vascular symptoms responded to very minor dose changes of levothyroxine (T4), likely because of the quick response of my Deiodinase Type 3 enzyme that was overactive at the time (Reverse T3 levels were 33 ng/dL, far above a reference boundary of 25).
Over the three months, the frightening pains sent me three times to the hospital Emergency. Each of those three times, I was in distress within 48 hours after each tiny Synthroid dose increase back up toward my normal 112-125, such as from 100/112 on alternating days, to a dose of 112 per day.
After passing multiple heart tests, after which doctors were still left mystified, my cautious and responsible thyroid doctor finally agreed it was safe for me to begin T3 dosing.
My first day on 5 mcg of Cytomel T3 (liothyronine), my cardiovascular symptoms reduced by 70%.
I recovered fully within weeks after I transitioned to full T3 monotherapy.
What this crisis taught me about my body
As I read medical research publications, I can’t help but keep my own health experiences in the back of my mind. Every now and then I have stumbled upon another piece of the puzzle that helped explain the mysteries.
1. By pondering my laboratory history
Over the years after my health crisis, I occasionally pondered and analyzed my past laboratory data in light of thyroid science. I started to suspect that my thyroid lab test history from October 2013 to spring 2016 showed the signature of a global genetic defect in thyroid hormone metabolism. It looked like a “partial SBP2 deficiency” (Dumitrescu et al, 2010).
However, I revised my hypothesis after I obtained more of my laboratory history going back to 2011. It showed that my TSH, FT4 and FT3 lab data fit the parameters of a “poor converter” of T4 hormone without any functional thyroid tissue (Midgley et al, 2015). Clearly, a genetic problem as serious as the SBP2 defect cannot suddenly arrive during the 10th year of thyroid therapy at the age of 46.
It then seemed more reasonable to hypothesize that the same antibody that is associated with my ultrasound-demonstrated condition of Atrophic Thyroiditis, the TSH receptor antibody (TBAb), could be responsible for limiting the function of the two deiodinases that perform T4-T3 conversion in the human body (D1 and D2).
I may have had a TBAb antibody flare that arrived in Fall 2013 and continued until at least Spring 2016 when I began to transition from T4 monotherapy to T3 monotherapy. The details of my laboratory data and the scientific publications that support the hypothesis will have to wait for future posts.
It is still a puzzle that I did not become severely symptomatic or ill until 2016. The cause and effect can be reciprocal — an antibody may worsen T4-T3 conversion rates, but then subsequently, chronically low T3 levels may worsen health.
3. By thyroid therapy experiments
I observed that my FT3 levels became low and could not rise for three years. But as I gradually weaned off T4 dosing and gradually moved toward T3 monotherapy, my FT3 levels were SET FREE and able to rise above the lower boundary of reference. I simultaneously experienced relief from hypothyroid symptoms. The cardiovascular spasms and almost all other health problems gradually faded away.
In 2017 I tried to reintroduce T4 hormone. It failed. As I increased T4 dose and reduced T3 to make room for it, two things happened 1) I experienced increasingly severe cardiovascular spasms. 2) My FT3 hormone level fell low again and was imprisoned once more. It fell below reference where it had been for years on T4 monotherapy, even when much smaller amounts of T4 hormone are included within my therapy.
It seemed that due to my flawed thyroid hormone metabolism I had acquired an absolute “cap” on the level of T3 my body would maintain whenever a significant amount of FT4 is present in blood, and that was about FT3 = 3.4 pmol/L on my laboratory’s test that ranged from 3.5 to 6.5 pmol/L. It seemed as if there was a glass ceiling above which FT3 could not rise when a certain amount of FT4 in blood shifted my deiodinase activity in a dysfunctional way.
If my body is now limited to attaining a maximum of only 3.4 pmol/L supply of FT3 in blood while dosing T4 hormone, then no dose of T4 hormone would be both safe (low enough to avoid cardiovascular spasms) and effective (eliciting an overall euthyroid state). The safest and most effective thyroid therapy modality for me is now T3 monotherapy.
What life can be like on T3 monotherapy
Being virtually thyroidless and dosing T3 alone means I don’t have any T4 hormone flowing through my blood. (Gasp! Oh no! some will be shocked to read that.)
I’m not dying or sick because of lack of it. But of course it’s neither normal nor convenient to lack T4.
It’s better, easier and gentler to your body to have T4 floating around in blood waiting to be converted into T3 in cells all over your body every minute of every day. I envy the vast majority of human beings that are able to do this wonderful thing without much of a metabolic problem getting in the way.
If you are a rare person like me, living without any T4 hormone, you have to get all your T3 from dosing thyroid hormone medication instead of gradual T4-T3 conversion.
But here’s the crux. You’re living within a two week journey to the edge of a cliff, but you won’t want to ever get close to that cliff.
The science shows that after a week or so of complete withdrawal from T3 alone without a thyroid gland (and I’m virtually thyroidless with a 0.5 mL atrophied gland), the TSH will skyrocket, and then your body can plummet into a deep chasm of hypothyroidism. (See the literature on T3 therapy withdrawal for thyroid cancer patients. Some therapists put their patients on T3 monotherapy for a few weeks postoperatively, before radioiodine ablation of the remnant gland.)
If you stay in a T3-less state for too long without thyroid hormone therapy to rescue you, you’re in danger of myxedema coma (not really a true coma but a rather unresponsive dulled state of consciousness and illness). Of course, you can die if you’re not treated. Your body will shut down without T3 hormone supply to cells. It happens faster when you are on T3 alone without a thyroid gland, because T4 floats around in blood a lot longer, as the storage hormone.
It’s like I’m a type 1 diabetic who always needs to have a supply of insulin.
For safety, in case I am in an accident and rushed to hospital, I have a tiny note about my medication and dose always tucked into the handy waterproof wristband pill holder that my husband lovingly designed and 3D-printed for me.
On a daily basis, I am vigilant. I always have to make sure I get enough T3, and never too much for my body, and I have to make sure that I never, ever run out of T3 pills.
This is why the Pfizer Cytomel drug shortages and price hikes in Canada are a scary thing.
I can’t go back to T4 dosing. No other “thyroid agent” or combination of them works safely in me.
FINDING MY DOSAGE
When I first started the journey, I wasn’t sure what dose I would end up on. All I had was some ballpark estimates from other patients and the medical literature.
Some of my friends are on 60 micrograms /day of T3, others on 100/day or 120. I’ve read of high maintenance doses in the medical literature since the 1950s.
Chopra et al, 1973, for example, said of T3 monotherapy doses that “It is generally held that one must administer 50 to 100 mcg of T3 daily to hypothyroid patients to achieve a euthyroid state,” and that “75 mcg T3/day [is] probably a minimal dose to normalize serum TSH.”
However, Saberi & Utiger (1974) discovered in a small study of T3 monotherapy compared with T4 monotherapy that “in these 8 patients as a group, 50 mcg T3 was not adequate replacement.”
I was formerly maintained on 112 to 125 mcg/day on T4 monotherapy, but I wasn’t converting well, so I’m doubtful that was a good index. It was raising to 137 mcg that first triggered my three months of cardiovascular spasms, so going higher would not have been healthy.
Like any thyroid patient starting out, I would get tested every 3 months. But between lab tests, I had to go safely and step by step toward my optimal daily T3 dose by charting my ongoing “vital signs” like heart rate and body temperature, and by reading Paul Robinson’s books (see Reference list below) and learning from T3 patient support forums. I had setbacks along the way but I learned as I went.
As I gradually lowered my T4 dose and added T3, I made 5mcg increases of T3 every two weeks and lowered my T4 by 10-15 mcg or so. Some people raise 5mcg per week, but in light of my awful cardiovascular symptoms on Synthroid, I and my thyroid doctor wanted to be very gentle and cautious.
I didn’t experience any adverse responses at all while raising T3 and tapering off T4.
After I stopped dosing T4, I became more hypothyroid, so my T3 dosing had to escalate further. It’s interesting to speculate about what is going on in the body at that point, when the body adjusts fuel sources from a combination T4-T3 to T3-only, but it’s a noticeably bigger shift.
I plateaued for many months on 47.5 mcg/day (mcg = micrograms), which I later learned wasn’t enough. Like many doctors and patients, I was afraid of going over the upper reference boundary for Free T3, not fully realizing yet that those laboratory boundaries are meant for people who also live with T4 concurrently in blood. I wasn’t sure what my ideal heart rate or body temperature was supposed to be because it varies for each person.
As a result of caution and inexperience, but also as a natural result of adjusting any therapy to an individual, in the early stages I only attained a level of thyroid support at T3 47.5 mcg that wasn’t enough. It wasn’t that different from my quality of life on T4 before I got sick, though it was in fact on the hypothyroid side, with continual lupus-like acne rosacea and lower body temperature. I was struggling at night with cold feet, going to bed shivering and wearing leggings and socks.
I had been used to this. It was my old, familiar, non-optimal “normal.”
Then a severe winter episode came to Calgary that taught me where I stood at that dose. One night after walking 10 minutes to my car in the cold, I couldn’t warm them up for the next 6 hours. My feet experienced a bad bout of Raynaud’s phenomenon, poor circulation and very cold and numb from mid-calf down. Even after soaking in a warm bath, they got cold again after I went to bed. I knew it was my thyroid dose being too low, given the context of my other cold-sensitivity symptoms and how my autoimmune conditions worsen in a hypothyroid state.
I gradually and cautiously raised to 75 mcg/day while checking vital signs carefully along the way.
It was very good for three months, then springtime came. It became too much of a dose for late spring / early summer. I gradually developed hand tremors and weak legs. I had to cut back for a couple of months to 62.5/day and I was fine. Then I needed to increase again to 75/day come Aug/September.
So I now vary between 62.5 and 75 mcg/day, generally reducing only for about 3 months or so in the summer. It’s August, yet I need 75 /day right now, so it’s not perfectly aligned with seasons, and it may be affected by factors beyond the seasons.
My doctor trusts me to make these adjustments within my prescribed dose. I’ve been given enough leeway.
This is ethical and respectful. It’s also practical, cost-effective, and … medically necessary. In T3 monotherapy, you have to trust an educated patient to do the micromanaging, to know how to read their own bodies, and to be wise enough to reduce when the body clearly says to reduce, and to increase when it says so. The patient should not have to be hand-held every step of the way — they should be given education and peer support, like a diabetes patient.
It’s also demeaning and unnecessary to put a person on a too tight leash of an insufficient T3 prescription and treat them like a drug addict. Tell me, who enjoys feeling weak, trembly, fatigued, hot, tense, and scatterbrained when overdosing themselves? Do Graves’ disease patients enjoy their excess thyroid hormone supply? Of course not.
The healthy body adjusts its own dose T3 daily from the “pharmacy in the neck” plus T4-T3 conversion throughout the body, but you’ll not see much of a blip in their FT3 blood tests because rates of secretion and conversion adjust for this very reason — to keep FT3 steady!
The healthy-thyroid body actively adjusts whatever it needs to, to “defend plasma T3” (Abdalla & Bianco, 2014).
If you’re curious how my dose relates to my body weight, I’m about 118 lbs. / 53 kg, so that is about 0.64 mcg per lb / 1.41 mcg per kg for me — but we all absorb differently via GI tract and metabolize differently when dosing, so different people will need more or less.
INACCURACY OF PHARMACEUTICAL CONVERSION ESTIMATES
I learned that the pharmaceutical conversion estimates supplied by product monographs are grossly inaccurate. They have no idea of the real potency of T3 dosing compared to T4 dosing in a long-term monotherapy context.
According to the ERFA dessicated thyroid monograph my 75mcg of T3 Cytomel is equivalent to 300 mcg of T4 / levothyroxine. The Cytomel product monograph suggests the same. HA! No way. Before the change, I was near or at the top of the FT4 range on 112/125 Synthroid. Now they say I’m on the equivalent of 300? That’s absolutely absurd, unrealistic and laughable based on my experience and all the patients in the T3-monotherapy community!
Why is their estimate of 25 mcg T3 = 0.1 mg (100mcg) T4 equivalent such a gross overestimate?
First of all, what are they basing the equivalence on? Likely an assumed Free T3: Free T4 ratio in blood patients like me do not have, or perhaps even the degree to which T3 dosing begins to powerfully oversuppress TSH — it starts to do this at a different T3 monotherapy dose for each person.
A pharmaceutical estimate of a static physiological equivalence of T3 micrograms to T4 micrograms is based on NO data from real T3 monotherapy therapeutic studies such as those done in the 1980s (Busnardo et al, 1980, 1983) — No, they throw thyroid therapy scientific history in the dustbin.
Instead, they often derive their ratios from the current protocol of single-dose pharmacokinetic studies in people with healthy thyroids who don’t need thyroid therapy, who concurrently have an abundant T4 supply continually converting to T3 in their cells!! (Jonklaas et al, 2015)
Next, such a pharmaceutical estimate does not take into account the fact that deiodinase enzymes shift their roles and interact very differently in the context of T3-only therapy.
Deiodinase Type 3 will likely dominate and remain upregulated when its favored substrate T3 is overabundant (whether or not you are thyrotoxic, T3 will be far more abundant than it would be if you had a well-regulated thyroid also supplying T4).
This D3 enzyme will be turning a larger percentage of dosed T3 into T2 as it crosses the cell wall, and this action happens within cells.
Therefore, in T3-only dosing, you must dose in a way that counteracts D3’s role in catabolizing the medication at this higher rate, or else the medication will be ineffective at getting T3 molecules past D3’s minefield and into their receptors in cell nuclei. (See the D3 “minefield” within a cell in Bianco, 2019’s illustrations.)
The abundant T3 hormone upregulates Deiodinase Type 1, which now has no T4 to convert to T3 and no RT3 to take apart, but it still remains active in deiodinating T3S (T3 sulfate), a T3 metabolite it focuses on. The T3-driven upregulation of D1 may enhance D1’s other deiodinating roles that are less emphasized in normal physiological states. (Bianco, 2019)
Deiodinase Type 2 of course has no T4 to deiodinate into intracellular T3 in this context, but it still functions to remove iodine from the outer ring of T3, turning it into T2. (Chatzitomaris et al, 2017). This could be yet another way that T3 dosage is drained away or dampened in its physiological effects. But at what higher or lower rate D2 takes apart T3 in the context of T3-only dosing is unknown. D2 certainly lacks T4’s presence to trigger D2 deactivation via ubiquitination.
The conversion rate of T3 to Triac will also increase in the presence of T3 levels that fluctuate and are slightly higher than the body would normally expect in the presence of T4. Triac is active in the T3 receptor, but Triac has a much shorter half-life than T3. (Gavin et al, 1980; Groeneweg et al, 2017)
Therefore, scientitsts must account for the higher percentage of “Intracellular Free T3 loss” to these other metabolites that normally occur in the body.
In addition, when you have more T3 in your body, the clearance rate of T3 in urine and feces will undoubtedly increase to a larger extent. (Bianchi et al, 1978)
The percentage of T3 that must be free vs. bound T3 within blood may adapt, and perhaps the transporters that bring T3 in and out of cells may shift their expression in the absence of both T4 and RT3 hormone.
Science still hasn’t explored and published all the adaptive aspects of human T3 monotherapy, but it has given these clues as a basis for scientific hypothesis-building.
Fears of overdose at “supraphysiological doses” of T3 are overblown, unscientific, taken out of context, and most importantly, are countered by the daily experience of patients on T3 monotherapy for years or decades.
This is a very important part of my life.
Some people like me metabolize T3 quickly and need to multi-dose, while others can get away with 3 doses a day or less.
I take 4 to 5 doses of T3 hormone a day, every 4 hours from 5:30 am (before rising at 7:30) until 9:30pm. I have gradually arrived at this after 3 years of tweaking.
I have many pill-alarms and a routine, but I have to adjust them if I change my work schedule, have a social event like a concert, and so on.
If I delay a dose by 2 hours, I have to shift my subsequent doses for the day forward, so I have some “delayed dose” alarms already set up to turn on if that happens.
I find multi-dosing helps to minimize the ups and downs of a rollercoaster ride of T3 hormone supply between doses.
As a general rule, I tend to dose so that I am never crossing the upper physiological boundary into any thyrotoxic symptoms, but I must dose to maintain intellectual function, which is the first to suffer diminution under less-than-optimal T3 conditions.
Total T3 has a short half life in blood. They say its half life is 12 to 24 hours, but that’s not a steady decline from a peak. The true shape of the Free T3 curve has a steep rise and fall in the first 6 hours. If you’re on T3, you and your doctor need to know the shape of the curve. My Free T3 peak appears to happen at 1.5 to 3 hours post dose, followed by a steep decline by 5 hours, then a long tail of gradual reduction in levels (Compare with graphs in Jonklaas et al, 2015). Many factors can tweak the T3 curve, peak, and overall half life.
Many doctors seem fearful of this Free T3 fluctuation in blood. Why? Is there any proof that it’s harmful when you can minimize it by multi-dosing? Show me the science instead of just fearing the unknown. It’s like ancient doctors and their fear of female hormone fluctuations, like the “wandering womb” theory of hysteria.
Just think. T3 has a half-life way longer than insulin’s half-life of 7 minutes, and people dose insulin without dropping dead.
Of course I forget to take a dose sometimes. Of course I pay the price after I gradually, unnoticeably fade into a hypothyroid state within hours after the scheduled dose time and my brain slows down.
Every time I experiment or make a mistake in dosing, I learn how my body responds. I have experienced mild hypothyroidism far more frequently than mild thyrotoxicosis, but I’ve experienced both many times over the past 3 years.
In general, my first symptom of hypothyroidism is cognitive slowdown, and it starts to happen even 5 hours after one of my 15mcg doses. This could be because scientists have proven that the D3 deiodinase dominates in the brain, and its favorite hormone to attack and destroy (its main “substrate”) is T3 hormone.
Eventually at about 8-10 hours post-dose, an hour passes as if it were ten minutes while I’m focused on a task I can’t quite complete, like writing something. I write and rewrite a single email to a student, just like I would often write and rewrite a single paragraph of my PhD thesis draft back in 2001 when I was still undiagnosed and hypothyroid. I’m in a zone, fading, and sometimes it takes some hours for the reality to sink in.
That’s the main risk, not the thyrotoxic side that raises red flags and shouts at you. It’s the silent creep into the hypothyroid side that is the risk. You’re like a frog in slowly freezing water.
I usually realize what I’ve done, what state I’m in, and I’m 4-6 hours behind schedule, but I can’t take a double dose safely because I metabolize fast.
If I don’t notice I’m slipping, eventually my heart rate also slows down. Then my body temperature gets cold, especially my feet and hands. I eventually have body-wide shivering episodes in a normal temperature room and have to get a sweater and turn on a space heater. I will often experience some emotional distress in the form of anxiety and self-accusing thoughts, which were far more common and extreme before T3 therapy.
Why don’t I notice? Besides the fact of the “long tail” of the T3 half-life curve, consider this: I spent 13 years on an ineffective T4 thyroid therapy, and before that, years of being un-diagnosed. Since my late 20s, I spent many more years being habituated to being hypothyroid than being truly euthyroid.
Plus, when you’re in that fading state, It’s hard to be aware of your body. Your brain is not processing the input properly. This is why “brain fog” is a perfect metaphor. Sometimes you can’t see the fog itself through the fog.
By 15 hours after a dose, I am falling into more overt hypothyroidism. I start to experience disorientation, short term memory problems, drowsiness, slow movement, and I repeat what I’ve said or struggle to find the words. I feel like the air has become thicker and I’m swimming through it to move around the house.
Recovery after a longer-than-normal 18 hour fast from T3 (i.e. overnight plus delaying or forgetting a dose or two) takes about two days, but it can have effects on the next few weeks. This is because some tissues exchange at far slower rates with Free T3 in blood, and they may notice the significant “dip” in net FT3 levels like an earthquake or a tsunami from afar. I’ve had mid-cycle menstrual spotting, UTI infections, slower skin-wound healing time, dry skin and nails and hair, dry eyes, and autoimmune condition flare-ups like my vertigo and uveitis.
Why would anyone with multiple autoimmune disorders do well with even a temporarily limited Free T3 supply?
On the thyrotoxic side, I don’t have as much experience.
For example, once I tried to take three doses of 15 mcg each spread out over 5 hours instead of 8 hours. Two hours after the third dose, I experienced mild hyperthyroid symptoms of nervousness, disconnected quick thought, faster heart rate. It was generally unpleasant, like being constantly on edge and under pressure. A rise in T3 levels will often overstimulate the secretion of cortisol or adrenaline. It can demand more blood sugar and create shakiness from hypoglycemia if you haven’t eaten in a while. A constant state of stress is not a state of ecstasy or pleasure. Although it overstimulates parts of the body, it is different from drinking too much coffee.
Each body is different, but a clear sign of overdose for me is hand tremor. It is easy to see when holding my arm out with a piece of paper in my hand for even 5 seconds. I see it with shaking weak legs when descending one flight of stairs from bedroom to main floor. Legs and arms lose some muscle mass. I’m fatigued. That’s mild thyrotoxicosis, and I backed off as soon I saw it.
FT3 THYROID LEVELS AT OPTIMAL DOSE
First I’ll talk about my thyroid lab results, then other biomarkers.
I need much more Free T3 flowing through my blood than normal people who have a normal amount of Free T4 in blood alongside their Free T3.
The most important role of Free T4 is to act as a flexible-rate, sustained-release “T3-delivery system” to your cells.
In most people, every day, some of their T4 converts to T3, and some converts to Reverse T3 (RT3), within each organ and tissue in their body.
There’s an average body-wide T4-T3 conversion rate of 27.3 to 35% in healthy people. (Cavalieri & Rapoport, 1977; Pilo et al, 1990)
On average, blood may carry 3.3 times as much Free T4 for every unit of Free T3. For example, Free T4 = 15.4 pmol/L and Free T3 = 4.6 pmol/L. (Marwaha et al, 2013; see also Cai et al, 2016)
I don’t have any Free T4 delivering a flexible rate of freshly-converted T3 to my cells every minute of every day.
I have to make up for the “Free-T4-that-could-have-become-T3” after it was transported from bloodstream into tissues and cells.
All things considered, my peak Free T3 has to be well above reference to compensate for lack of Free T4, and my average Free T3 hovers around the upper limit of reference.
That’s where “euthyroidism” is when you don’t have any T4 — it shifts the euthyroid FT3 range higher than the normal reference range.
Twelve hours after my evening dose, in a morning blood draw, my FT3 level has varied from 4.5 to 6.6 (3.5 – 6.5 pmol/L). That’s my baseline / lowest level during the day. Keep in mind that I dose 5x a day.
The highest FT3 reading I’ve ever had was not representative, but rather a mistake that I made as part of trial and error while trying out a slow-release version of T3 for part of my dose. It was 12.2 pmol/L. Way too high. But I also tested 4 hours post-dose, so that’s a sign of the peak Free T3 curve at its highest, not a constant level. Plus, this was after a larger dose than I normally take now, while I was dosing only 3 times a day, including once a day with a 25mcg slow-release T3 powder capsule.
My doctor asked me to re-test right away after the 12.2 result. Three days later, at 15 hrs post dose, it was 5.8 pmol/L. That was when I was mildly thyrotoxic in symptoms, with mild tremors, so of course I cut back! This is why an occasional Free T3 lab test is helpful confirmation of symptoms and is absolutely necessary for safety.
Just how harmful are minor, temporary glitches on the road to optimizing T3 therapy?
Thyroid scientists have discovered that the human body can handle very wide daily fluctuations above the normal Free T3 range without tissues becoming thyrotoxic. Even large peaks and valleys can become “attenuated” or moderated within tissues (Saberi & Utiger, 1973).
As Free T3 enters tissues, it’s not just being forced into cellular receptors. The body continues to metabolize T3 into other useful hormones like Triac and T3 sulfate.
There’s a “fire-fighter” everywhere in our bodies called Deiodinase Type 3 that focuses on breaking apart excess T3, capable of increasing its activity in any tissue in the human body as required (Bianco, 2019). This D3 enzyme converts a flexible rate of T3 into T2. It protects the body from transient thyrotoxicosis due to T3 fluctuations. That’s its healthy role.
Science also suggests T3 hormone may lose some of its usual potency at receptors when you lack T4. Consider the far shorter duration of time of T3 binds to receptors when it’s not converted locally from T4 by the D2 enzyme within the cell (Bianco, 2019). Some molecular biologists have theorized the nuclear T3 receptor’s sensitivity and/or “availability” may be dulled when T4 is not binding to integrin receptors on the outside of the cell’s wall (Hammes & Davis, 2015).
If peak levels and average levels of Free T3 are too high for these protective factors to manage, excess will manifest in signs and symptoms to signal the need for a change.
WHAT ABOUT MY TSH?
My Free T3 has to be therapeutically and adaptively high, so it completely suppresses my TSH.
Natural metabolites of T3 are capable of inducing benign hormone-induced central hypothyroidism, a lower than normal TSH.
T3-monotherapy patients will inevitably convert more T3 to Triac. One study estimated 14% of daily dose conversion to Triac in three patients on T3 monotherapy (Gavin et al, 1980). Triac is well known as a metabolite that exerts T3-like effects but more powerfully suppresses TSH (Mirell et al, 1989).
Another natural T3 metabolite that is known to suppress TSH more powerfully is the active form of T2, a hormone associated with increased body temperature and energy expenditure (Louzada & Carvalho, 2018; Lombardi et al, 2015). The T3 hormone is still capable of deiodination to this form of T2 via Deiodinase Type 2, and there’s a lot more T3 available for conversion into T2.
Because of these and other adaptive factors, very soon after scientists started to study T3-dominant therapies, they learned that T3 could suppress TSH without causing thyrotoxicosis. In the context of T3-T4 combination therapies, TSH can be more powerfully suppressed by small dose changes as one gets closer to approaching an euthyroid dose (Snyder & Utiger, 1972).
This power of T3 to oversuppress TSH is confirmed by the common experience of people on T3-dominant therapies. In fact, my TSH was suppressed long before I achieved an optimal dose, while I was on my way tapering off T4 hormone.
One can assess whether a T3 monotherapy dose capable of suppressing TSH is nevertheless clinically euthyroid by attending to FT3’s effect on a variety of clinical biomarkers and symptoms (Busnardo et al, 1980, 1983).
Here are some of my non-thyroid lab results before and after my transition.
Nothing much was abnormal before or after changing my therapy besides my TSH and thyroid hormones, thyroid antibodies (I tend to be mildly elevated in TG antibody), and some of the markers below.
These numbers are from 1 year to 3 months BEFORE the switch that occurred in April 2016, vs. two years AFTER the switch from T4 therapy to T3 therapy, while I was on 75mcg T3 monotherapy in 2018:
Bilirubin, total: Before, 7 – After, 10. (8.0-35.0 U/L) — MILD RISE
WBC: Before, 7.8 – After, 5.1 (4.0-11.0 10E9/L) — MILD FALL
ALT Alanine transaminase: Before, 32 – After, 15 (1.0-40.0 U/L) — SIGNIFICANT DROP
Alkaline phosphatase: Before, 31 – After, 63. (30-115 U/L) — SIGNIFICANT RISE
Ferritin: Before, 83 – After, 68 (13-375 ug/L) — MILD FALL
Iron: Before, 12 – After, 21 (6.0-28.0 umol/L) — SIGNIFICANT RISE
Here are my HUGE reductions in cholesterol. This is known to occur on T3 therapy.
Total cholesterol: Before, 6.57 – After, 3.78 (3.80-5.20 mmol/L) — EXTREME DROP
LDL cholesterol: Before, 4.35 – After, 1.79 (2.00-3.40 mmol/L) — EXTREME DROP
This is another characteristic T3-monotherapy change:
Sex Hormone Binding Globulin (SHBG): Before, 89 – After, 130 (20-100 nmol/L) – EXTREME RISE
Commentary on this SHBG result:
“Men had less increase in SHBG than women when treated, and the most marked increase was with 200mcg T3.” (Cavaliere et al, 1988)
“The substitution of l-T3 for l-T4 caused a significant reduction in lipid parameters. These data suggest that the TH action is increased in the liver, and the SHBG increase supports this hypothesis. The changes in serum lipid metabolism parameters are similar to the effects observed with drugs approved for the treatment of dyslipidemia (35) or TH analogs (36). The increase in liver TH tone could be due to a first-pass effect because orally delivered l-T3 presumably produces higher concentrations in the liver than in other organs. This differential response appears to be limited to the lipid metabolism and SHBG, whereas no differences in indices of insulin resistance were detected. This is remarkable because hyperthyroid states are associated with an increase in hepatic gluconeogenesis (37), and overt thyrotoxicosis is a known cause of secondary diabetes.” (Celi et al, 2011)
In other words, while my Cholesterol lower and SHBG rise may seem like a symptom of thyrotoxicosis, that is contradicted by the fact that I have no problems at all in my Glucose or Hemoglobin A1C. There are no serious health consequences for mildly elevated SHBG or a cholesterol mildly below reference.
Indicators of blood glucose / insulin sensitivity are normal. While I was low T3 I had to go on a moderately low-carb high fat diet to manage my weight. As I went from 47.5 mcg to 75 I noticed that I was able to handle more carbohydrate intake without gaining fat, so my T3 meds were helping me metabolise carbs.
Glucose, fasting: Before, 4.8 After, 5.5 (3.3-6.0 mmol/L). — MILD RISE
Hemoglobin A1C: Before, 5.2 After, 5.1 (4.3-6.1%) — NO DIFFERENCE
NO OTHER CHANGES.
All the other results hardly moved their levels within the normal reference range. Unremarkable.
I did a thorough check to be sure I was not imbalancing anything major with my therapy. My general practitioner is an MD and a Functional Medicine doctor. I paid for a huge amount of tests of all kinds. Nothing much is wrong with me but my bizarre thyroid issues and autoimmunity. For the vast majority of test results I have only “after” data, not “before and after” data.
GI tract function is a bit on the hypothyroid / constipated side and I still struggle to get enough stomach acid, so I take hydrochloric acid pills once a day with food.
I’m gluten-free since 2012 and I now have a strong allergic and GI response to accidental ingestion of gluten. I carry a significant Celiac risk gene but no celiac diagnosis. I have done some exploration of the science in the area of autoimmunity and gluten-free diets and I currently believe it is beneficial for people with autoimmune diseases to eliminate gluten. I recommend this excellent lecture video “The Gut is Not Like Las Vegas” by gluten & Celiac researcher Dr. Alessio Fasano, and his scientific article in the references below.
My vital signs and metabolic rate are normal. Body temp normal.
Blood pressure normal, but at home when I test, it is usually on the very low side of normal.
No tremors. Good muscle strength.
As for mental health, I’m calm and reasonable, emotionally balanced and sociable.
I sleep at night a normal amount, and I can also stay up late if I want to.
I’ve got 6 or 7 autoimmune conditions including Ankylosing Spondylitis, but they are mostly in remission and rarely flare up now.
I’m very healthy for an almost-50-year-old, considering all I’ve been through with health challenges throughout my life.
Overall, my three plus years so far on T3 therapy have been better than all the 13 years I spent on Synthroid and the health challenges I experienced 15 years before that.
This is what life is like as a thyroidless person who depends on T3 alone. A challenging balancing act, something that I have to be conscious about every day.
But I would not have it any other way.
I’m so grateful to have my thyroid therapy fixed! It’s so fundamental to my overall health.
CONCLUSION: THE ABNORMAL MAY BE ADAPTIVE
Before I got sick, I thought I was just a normal thyroid patient, if there is such a thing.
My thyroid therapy on Synthroid was far from optimal, but medicine is willing to forgive a multitude of sins within standard thyroid therapy. I and my doctors attributed so many of my chronic hypothyroid symptoms to the daily stresses of life, aging, not enough exercise, being overweight (until 2012), personality quirks, and most of all, we blamed my other autoimmune conditions.
I would never have dreamed that having a low T3 during a major autoimmune flare-up would send me to the hospital over and over in agony.
I would never have dreamed I’d need such a change.
I never dreamed that I’d have to research my own thyroid and autoimmune and cardiovascular health so deeply to find a solution and scientific explanations, because doctors are still so clueless about the power of T3 hormone.
When a thyroid disability is complex, like when it combines with a thyroid hormone metabolic dysfunction, thyroid transport dysfunction, or a receptor sensitivity problem, a major shift in thyroid levels enables you to attain truly normal biomarkers and health outcomes.
I am not sure why everyone must conform to a standard model of therapy. A one-size-fits-all therapy model doesn’t fit everyone. We can each have a complex, unpredictable, individual response to thyroid medication.
It’s not the patient’s fault when T4 monotherapy fails.
There are so many ways a T4 therapy can fail to adapt to diverse human biology. It’s not just because of liver injury or intolerance to T4 pharmaceutical fillers, which are the two commonly blamed causes of T4 intolerance.
It can fail mildly and chronically for years, then fail catastrophically in a time of illness.
In addition, T3-T4 combination therapies at a wide variety of ratios, whether 1:16 or 1:4 or 1:2, can still fail to meet the demands of diverse human biology. The idea of a single correct ratio, a mono-combo-therapy, is a paradox of pharmaceutical rigidity imposed on the reality of metabolic flexibility.
The question is — is the biochemical “new normal” truly adaptive or maladaptive? In other words, is it truly therapeutic or harmful? Is it justifiable?”
Some people, few indeed, who are both thyroidally and metabolically disabled within a rigid therapeutic model — unable to move past unacceptable health barriers, will actually need an adaptation as extreme as an electric wheelchair.
In a fragile health context, a chronic low(er) T3 is a major health vulnerability. You don’t know how close a person can be to falling through the thin ice of a T3 level too low for their body’s basic requirements.
Nobody should be left vulnerable with a chronic low Free T3 for months or years on end. Nobody, not even the person with the perfect thyroid hormone metabolism. Not even the thyroid-healthy. Nobody!
My therapy will likely be troubling and offensive to many doctors because I don’t fit within any of the statistically-derived TSH, FT3 or FT4 reference range boundaries.
Some will think my therapy is dangerous for that reason alone.
That’s unfortunate, given all my other biomarkers and health outcomes. I would be in far more danger, perhaps not alive today, had I continued with T4-only therapy during a worsening health crisis.
To those who are offended or troubled by my metabolic adaptation I say this:
“Don’t be offended by my unique medical disability and the size of the T3 wheelchair I need.”
“Expand your mind to include people like me in the diverse world of disease and health. Don’t narrow your mind to exclude my disability or its accommodation.”
To my fellow thyroid patients, I ask for nothing more than this: “Respect your colleagues who need this mode of therapy, even if you personally don’t depend on T3 monotherapy. Some day you or someone you love might need it. Do all you can to make sure this therapy remains an option on the table for me and other people who need it.”
- Tania S. Smith
Abdalla, S. M., & Bianco, A. C. (2014). Defending plasma T3 is a biological priority. Clinical Endocrinology, 81(5), 633–641. https://doi.org/10.1111/cen.12538
Bárez-López, S., & Guadaño-Ferraz, A. (2017). Thyroid Hormone Availability and Action during Brain Development in Rodents. Frontiers in Cellular Neuroscience, 11, 240. https://doi.org/10.3389/fncel.2017.00240
Bianchi, R., Zucchelli, G. C., Giannessi, D., Pilo, A., Mariani, G., Carpi, A., & Toni, M. G. (1978). Evaluation of triiodothyronine (T3) kinetics in normal subjects, in hypothyroid, and hyperthyroid patients using specific antiserum for the determination of labeled T3 in plasma. The Journal of Clinical Endocrinology and Metabolism, 46(2), 203–214. https://doi.org/10.1210/jcem-46-2-203
Bianco, A. C., Dumitrescu, A., Gereben, B., Ribeiro, M. O., Fonseca, T. L., Fernandes, G. W., & Bocco, B. M. L. C. (2019). Paradigms of Dynamic Control of Thyroid Hormone Signaling. Endocrine Reviews, 40(4), 1000–1047. https://doi.org/10.1210/er.2018-00275
Blankenberg, S., Rupprecht, H. J., Bickel, C., Torzewski, M., Hafner, G., Tiret, L., … Lackner, K. J. (2003). Glutathione Peroxidase 1 Activity and Cardiovascular Events in Patients with Coronary Artery Disease. New England Journal of Medicine, 349(17), 1605–1613. https://doi.org/10.1056/NEJMoa030535
Boix Carreño, E., Picó, A., Zapico, M., López, A., & Mauri, M. (2007). Outcome of pregnancy in a hypothyroid woman with resistance to thyroid hormone treated with triiodothyronine. Journal of Endocrinological Investigation, 30(3), 253–255. https://doi.org/10.1007/BF03347434
Busnardo, B., Bui, F., & Girelli, M. E. (1983). Different rates of thyrotropin suppression after total body scan in patients with thyroid cancer: Effect of an optimal saturation regimen with thyroxine or triiodothyronine. Journal of Endocrinological Investigation, 6(6), 455–461. https://doi.org/10.1007/BF03348345
Busnardo, Benedetto, Girelli, M. E., Bui, F., Zanatta, G. P., & Cimitan, M. (1980). Twenty-four hour variations of triiodothyronine (T3) levels in patients who had thyroid ablation for thyroid cancer, receiving T3 as suppressive treatment. Journal of Endocrinological Investigation, 3(4), 353–356. https://doi.org/10.1007/BF03349370
Cai, J., Fang, Y., Jing, D., Xu, S., Ming, J., Gao, B., … Ji, Q. (2016). Reference intervals of thyroid hormones in a previously iodine-deficient but presently more than adequate area of Western China: A population-based survey. Endocrine Journal, 63(4), 381–388. https://doi.org/10.1507/endocrj.EJ15-0574
Cavaliere, H., Abelin, N., & Medeiros-Neto, G. (1988). Serum levels of total testosterone and sex hormone binding globulin in hypothyroid patients and normal subjects treated with incremental doses of L-T4 or L-T3. Journal of Andrology, 9(3), 215–219. https://doi.org/10.1002/j.1939-4640.1988.tb01038.x
Celi, F. S., Zemskova, M., Linderman, J. D., Smith, S., Drinkard, B., Sachdev, V., … Pucino, F. (2011). Metabolic effects of liothyronine therapy in hypothyroidism: A randomized, double-blind, crossover trial of liothyronine versus levothyroxine. The Journal of Clinical Endocrinology and Metabolism, 96(11), 3466–3474. https://doi.org/10.1210/jc.2011-1329
Chatzitomaris, A., Hoermann, R., Midgley, J. E., Hering, S., Urban, A., Dietrich, B., … Dietrich, J. W. (2017). Thyroid Allostasis–Adaptive Responses of Thyrotropic Feedback Control to Conditions of Strain, Stress, and Developmental Programming. Frontiers in Endocrinology, 8. https://doi.org/10.3389/fendo.2017.00163
Chopra, I. J., Solomon, D. H., & Teco, G. N. C. (1973). Thyroxine: Just a Prohormone or a Hormone Too? The Journal of Clinical Endocrinology & Metabolism, 36(6), 1050–1057. https://doi.org/10.1210/jcem-36-6-1050
Dumitrescu, A. M., Di Cosmo, C., Liao, X.-H., Weiss, R. E., & Refetoff, S. (2010). The syndrome of inherited partial SBP2 deficiency in humans. Antioxidants & Redox Signaling, 12(7), 905–920. https://doi.org/10.1089/ars.2009.2892
Fasano, A. (2012). Zonulin, regulation of tight junctions, and autoimmune diseases. Annals of the New York Academy of Sciences, 1258(1), 25–33. https://doi.org/10.1111/j.1749-6632.2012.06538.x
Gavin, L. A., Livermore, B. M., Cavalieri, R. R., Hammond, M. E., & Castle, J. N. (1980). Serum concentration, metabolic clearance, and production rates of 3,5,3’-triiodothyroacetic acid in normal and athyreotic man. The Journal of Clinical Endocrinology and Metabolism, 51(3), 529–534. https://doi.org/10.1210/jcem-51-3-529
Groeneweg, S., Peeters, R. P., Visser, T. J., & Visser, W. E. (2017). Triiodothyroacetic acid in health and disease. The Journal of Endocrinology, 234(2), R99–R121. https://doi.org/10.1530/JOE-17-0113
Hammes, S. R., & Davis, P. J. (2015). Overlapping nongenomic and genomic actions of thyroid hormone and steroids. Best Practice & Research Clinical Endocrinology & Metabolism, 29(4), 581–593. https://doi.org/10.1016/j.beem.2015.04.001
Jonklaas, J., Burman, K. D., Wang, H., & Latham, K. R. (2015). Single Dose T3 Administration: Kinetics and Effects on Biochemical and Physiologic Parameters. Therapeutic Drug Monitoring, 37(1), 110–118. https://doi.org/10.1097/FTD.0000000000000113
Lombardi, A., Senese, R., De Matteis, R., Busiello, R. A., Cioffi, F., Goglia, F., & Lanni, A. (2015). 3,5-Diiodo-L-Thyronine Activates Brown Adipose Tissue Thermogenesis in Hypothyroid Rats. PLoS ONE, 10(2). https://doi.org/10.1371/journal.pone.0116498
Louzada, R. A., & Carvalho, D. P. (2018). Similarities and Differences in the Peripheral Actions of Thyroid Hormones and Their Metabolites. Frontiers in Endocrinology, 9, 394. https://doi.org/10.3389/fendo.2018.00394
Marwaha, R. K., Tandon, N., Ganie, M. A., Mehan, N., Sastry, A., Garg, M. K., … Singh, S. (2013). Reference range of thyroid function (FT3, FT4 and TSH) among Indian adults. Clinical Biochemistry, 46(4), 341–345. https://doi.org/10.1016/j.clinbiochem.2012.09.021
Mirell, C. J., Yanagisawa, M., & Hershman, J. M. (1989). Triac reduces serum TSH without decreasing alpha and beta TSH messenger RNAs. Hormone and Metabolic Research = Hormon- Und Stoffwechselforschung = Hormones Et Metabolisme, 21(3), 123–126. https://doi.org/10.1055/s-2007-1009170
Mugesh research group at the Indian Institute of Science. (n.d.). Chemistry of the Thyroid Hormone Deiodination. Retrieved August 29, 2019, from Chemical Biology, including bioinorganic chemistry website: https://www.mugesh.org/research-3
Robinson, P. (2013). The Ct3M Handbook: Recovering adrenal health using the circadian T3 method. Elephant in the Room Books.
Robinson, P. (2018). Recovering with T3: My Journey from Hypothyroidism to Good Health Using the T3 Thyroid Hormone (Updated Edition 2018). Retrieved from https://opentrolley.com.sg/Book_Detail.aspx?EAN=9780957099340
Saberi, M., & Utiger, R. D. (1974). Serum Thyroid Hormone and Thyrotropin concentrations during thyroxine and triiodothyronine therapy. The Journal of Clinical Endocrinology & Metabolism, 39(5), 923–927. https://doi.org/10.1210/jcem-39-5-923
Sara, J. D., Zhang, M., Gharib, H., Lerman, L. O., & Lerman, A. (2015). Hypothyroidism Is Associated With Coronary Endothelial Dysfunction in Women. Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, 4(8). https://doi.org/10.1161/JAHA.115.002225
Snyder, P. J., & Utiger, R. D. (1972). Inhibition of thyrotropin response to thyrotropin-releasing hormone by small quantities of thyroid hormones. Journal of Clinical Investigation, 51(8), 2077–2084. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC292364/
Vella, K. R., & Hollenberg, A. N. (2017). The actions of thyroid hormone signaling in the nucleus. Molecular and Cellular Endocrinology, 458, 127–135. https://doi.org/10.1016/j.mce.2017.03.001
von Hafe, M., Neves, J. S., Vale, C., Borges-Canha, M., & Leite-Moreira, A. (2019). The impact of thyroid hormone dysfunction on ischemic heart disease. Endocrine Connections. https://doi.org/10.1530/EC-19-0096