Here I bring thyroid science into a discussion of effectively adapting and managing the most flexible form of thyroid therapy, T4-T3 combination therapy.
This is a model capable of adapting to an individual’s unique thyroid disability and response to thyroid medication.
Finding an individual’s optimal combination therapy is medically necessary when conventional T4 monotherapy fails to treat hypothyroidism due to
- poor T4-T3 conversion,
- or poor T4 absorption (Poor gastrointestinal health generally interferes more with T4 absorption than with T3: see Wiersinga et al, 2012),
or when a patient can’t tolerate or manage the delicate balance of T3 monotherapy.
Just as monotherapies don’t work for everyone, one magical T3:T4 ratio in medication won’t work for everyone. The idea of the “physiological ratio” modeled on statistically average thyroidal secretion rates is a medical idol based on a misreading of the scientific evidence (see our satiric post on Pilo et al, 1990: “Meet a person with the perfect T3:T4 thyroid secretion ratio“).
Instead of adhering to a rigid recipe, the purpose of combination therapy is to be flexible enough to adapt to the individual’s unique needs and metabolic handicaps, just as a real thyroid gland compensates for shortfalls in T4-T3 conversion.
Some patients will do fine with the 1:4.2 ratio found in desiccated thyroid, while others will need more T3 than desiccated thyroid provides, and some will need less.
Knowledge of the science behind what we’re doing helps us adapt our ratio, dose, and even the timing of our doses, to achieve better health outcomes.
Basic principles of flexible T3:T4 combination therapy
People often try to make thyroid hormone dosing imitate natural thyroid secretion. Scientists have tried to mimic a “physiological” ratio.
But nature is incredibly flexible. In health, thyroid secretion ratios are diverse from person to person. There is no single physiological dose ratio.
That is why secretion rates in people with healthy thyroids are best expressed as ranges, not statistical averages, as shown in this diagram (Wiersinga, 1979):
In the diagram above, the person is getting a different T4:T3 ratio of they have different ranges of secretion for each hormone:
- 22 nmol T3 and 116 nmol T4 per day, OR
- 66 nmol T3 and 116 nmol T4 per day
One of the most famous studies of T4 and T3 kinetics in healthy human beings showed how diverse the secretion ratios truly are:
If diverse people have diverse T3:T4 thyroid secretion ratios in health (and they do), and if people respond in diverse ways to T4 monotherapy (and they certainly do), then a range of diverse human beings is going to respond differently to any specific dose ratio of thyroid hormone therapy.
Adjustment of ratio and dose to the individual is the key to combination therapy dosing.
There’s more than one T3:T4 ratio in dosing that is safe, effective and therapeutic. It’s simply and clearly because there’s more than one kind of thyroid patient, especially when it concerns our thyroid hormone metabolism — the likelihood of a person’s deiodinases (thyroid hormone converting enzymes) becoming imbalanced and fighting against their current mode of thyroid therapy.
Are you a poor or good T4-T3 converter?
Thyroid hormone conversion rates also fall in a wide range, as you see in Wiersinga’s image above.
Our metabolism of T4 and T3 works differently when we have different degrees of thyroid gland loss, generally moving toward poorer T4-T3 conversion when you have less living thyroid tissue (Ito et al, 2015, Kawasaki et al, 2019)
Consider whether a person is a “good converter,” “moderate converter” or “poor converter” of T4 hormone — when you lack thyroid tissue, a thyroid metabolism handicap becomes much more evident, as proven by Midgley et al, 2015.
They examined the FT3 levels, FT4 levels, and TSH levels in people with no thyroid due to carcinoma (thyroid cancer, total thyroidectomy) and people with a range of thyroid gland function (AIT = Autoimmune Thyroiditis, such as Hashimoto’s).
In this graph below, the size of the box and length of line shows the degree of human variation in each group of patients.
When you are permitted to dose thyroid medication to suppress TSH, as you are in thyroid cancer therapy, the patient has a higher chance of getting more T3, unsurprisingly. But it’s a roll of the dice. Not everybody gains the same amount of T3 out of their T4 dosing because the diversity in T4-T3 conversion rates shows up more starkly in people without thyroids.
The red colored boxes are the poor converters in this graph.
If this is the diversity you see even on one limited mode of thyroid therapy, T4 monotherapy, you can reasonably predict that the diversity of human response to ANY thyroid therapy is going to be huger than the range of diversity seen in “normo-thyroid” healthy people.
The dosing ratio that works is the one that yields a healthy ratio and combination of Free T3 and Free T4 in blood for you. A “healthy ratio” means that it’s working with your individual thyroid hormone metabolism — the way your T4-T3-converting deiodinases work given your genetics and current health status.
There’s currently a myth going around on the Internet among patients that you can’t combine desiccated thyroid (NDT) with synthetic T4 because it will be “too much” T4 for the patient. Which individual patient would it be too much for? What are their current FT4 and FT3 and symptoms?
The opposite fear circulates among many doctors — “no one must ever add T3 to therapy to the extent of equaling or exceeding the ratio of desiccated thyroid, because that would always be too much T3.” Of course a person would need a higher T3:T4 ratio in dosing if they are a poor converter of T4.
Trying to fit yourself into a prescribed optimal box can be very counterproductive, like forcing yourself to wear a size 5 shoe when you need a size 8.
Flexibility should be the rule, as well as an understanding that the pituitary’s TSH and other tissues in your body can respond differently as you customize FT3 and FT4 levels.
How to optimize FT3 and FT4 levels
There is no single “optimal” place in the hormone reference ranges for all combination therapy patients.
That’s because the population reference ranges for TSH, T4, and T3 are based on statistics that cover a huge range of human diversity. Research has proven that Individual thyroid ranges are 38-68% the size of the lab reference range. One healthy person will reside near the top of range, and another near the bottom.
Our bloodstream concentrations provide unbound (free) thyroid hormones that can be transported into organs and tissues.
In cells, FT4 gets slowly converted into T3 every minute of every day, and T3 has activity in the nuclear receptors in the very core of your cells.
Then tissues’ FT3 and FT4 and other metabolites get exchanged back with the bloodstream supply for recirculation, riding out of cells on the same transporters that brought them into the cells. (Bianco et al, 2019; see their visualization of the cell’s exchange.)
A key concept here is that bloodstream hormone levels are transformed by tissues.
The amount of T3 and T4 flowing through blood is the reservoir that is exchanged with all tissues in both directions (the idea of a “hidden pool” of T3 in the body was logically dismissed in 1989 by Faber et al).
That means that what’s in your blood is
- partly based on your input (from medication and any thyroid function), and
- partly a representation of how your tissues have used and converted those hormones lately.
Think about T4 as nature’s slow-release delivery package for future T3 or RT3.
T4 is not a separate hormone, but a father of two potential hormones, and the ratio and amount you get of each (T3, versus RT3) is uncertain and unpredictable.
In contrast, free T3 is instantly active hormone for cells. Humans can live on T3 monotherapy without any T4 in blood because thyroid hormone sufficiency is largely synonymous T3 sufficiency at the cellular level.
This means, in application,
- 1) Everyone needs a minimum level of Free T3 in blood, and in health, it’s usually nowhere near the lower boundary of the FT3 reference range!
- 2) Permit a higher Free T3 to counterbalance low Free T4. That’s what biology does whenever T4 is lower.
The free T3 basement
The baseline Free T3 concentration in blood is a foundation of T3 thyroid hormone sufficiency in the body as a whole.
We can learn this powerful lesson from the condition of “low T3 syndrome” or “nonthyroidal illness syndrome” (NTIS).
In this syndrome, when Free T3 is quickly depleted to below-normal levels by a health crisis, your life is at risk, even if you have a healthy thyroid.
When nonthyroidal illness strikes in acute, critical illness, it is temporary. But that doesn’t mean it is benign. It’s temporary because people so often die or recover.
The FT3 is not usually kept chronically low, except in some chronic diseases like heart failure, liver failure, and kidney failure, and even in these illnesses, the outcomes are deadly the lower their T3 levels are. (See Ataoglu: Low T3 in critical illness is deadly, and adding high T4 is worse.)
This proves the basic law #1, “everyone needs a minimum level of Free T3 in blood.”
How does one recover from Low T3 syndrome?
At a certain phase in nonthyroidal illness, after not only your FT3 but also your Free T4 levels drop, TSH then has the metabolic permission to rise (why would TSH rise and add T4 from thyroidal secretion when there’s already a lot of T4 floating around?).
Something triggers the body “it’s time to heal now,” and your pituitary saviour TSH rises fast and high, stimulating a healthy thyroid gland to release a higher than average dose of T3 from the “pharmacy in the neck” to fill the FT3 hole in the bucket, supply but not overwhelm a person with FT4, and save that person’s life, and gently help tissues recover. (Peeters et al, 2005; Citterio et al, 2018)
What happens when a person doesn’t have thyroid gland tissue for TSH to overstimulate into hyper-T3 productivity during this low-T3 recovery phase? Abdalla and Bianco (2014) have also wondered! No answer. Silence.
This is awful. I can’t believe it either. I’ve looked and looked for years. Nobody knows how the thyroidless survive FT3 depletion because science has excluded the thyroidless from study of nonthyroidal illness on a mass scale.
There is no excuse for leaving a thyroid-disabled person too vulnerable, too close to their personal FT3 basement, for the rest of their lives, on poorly dosed, poorly adapted thyroid therapy of any type — It can happen on both monotherapies as well as combination therapy. Chronic low T3 can happen even while the TSH is normal or suppressed, because an isolated FT4 can singlehandedly keep TSH low while FT3 is depleted.
We have tissues and organs that depend largely on that direct, bloodstream source of T3 more than local T4-T3 conversion in cells. These are tissues such as our liver and kidney (Bianco et al, 2019). Those organs and tissues would truly suffer if you lowered FT3 too far. A fallacy has kept too many people T3-starved in thyroid therapy: Doctors saying “look at all that T4 in your blood! Your tissues CAN convert it, so of course they will convert ENOUGH.” No, that’s not fair to the tissues that depend largely on direct FT3 supply from blood.
Imagine a patient is a poor converter of T4 to begin with, perhaps genetically. Their vulnerable FT3-dependent organs can’t possibly develop a higher local efficiency of T4-T3 conversion that would compensate for someone stealing away their precious FT3 supply from blood.
Measure Free T3 in thyroid therapy and you’ll be far more safe from harm both from excess and deficiency of this most vital thyroid hormone.
Nature induces T3-dominant ratios
The “lower T4 higher T3” pattern in blood is part of normal thyroid biochemistry among people with healthy thyroids.
Look at FT3 and FT4 average levels and ratios in large population studies to see proof that a mild FT3 dominance over FT4 is nature’s norm. On average, Free T3 is 5 to 10% higher in its range than T4 is within its range (See a review of the science in “Normal FT3:FT4 thyroid hormone ratios in large populations.”
The contrast with the distorted ratio in LT4 monotherapy (on the right) is stark.
In addition, larger T3-dominant patterns are benignly adaptive in nature (higher T3:T4 ratios, where FT3 dominates over FT4 in blood, in relationship to their respective reference ranges).
This principle of the healthy T3-dominant thyroid hormone ratio is what has enabled the human race to survive local iodine deficiencies.
In iodine deficiency, T4 drops low, but a rising TSH saves your body from harm by ramping up T3 synthesis and conversion. People with low T4 and enlarged thyroids (goiter) can actually be euthyroid (Pharaoh et al, 1973). Isn’t nature smart? When you don’t have that many iodine atoms, your body has a way to shift production to more cheaper 3-iodine hormone molecules (T3) than normal, less costlier 4-iodine molecules (T4) than normal, and the T3 is the more direct, essential hormone, anyway.
This is also the basic principle that keeps a person non-symptomatic (without hypothyroid symptoms) while their thyroid gland slowly dies over years and decades, from autoimmune thyroid gland attack — before they pass the tipping point of too much thyroid tissue loss.
In untreated subclinical hypothyroidism, the body’s TSH rises in order to push slightly more T3 than normal out of the dying thyroid and drive up its ability to convert T4-T3 as blood flows through its tissues (Carpi et al, 1979).
This high T3:T4 ratio is naturally induced in subclinical hypo for a good reason. Just as in iodine deficiency, the body is doing everything it can to keep Free T3 afloat, above the Free T3 basement — the body’s metabolic minimum requirement for healthy function in every tissue and organ.
However, there are exceptions to this general principle of the healthy T3:T4 ratio ranging from mildly T3-dominant to highly T3-dominant.
Some people who fare well on T4 monotherapy or very low T3:T4 dosing ratios will get enough FT3 supply even though their blood is still very FT4-dominant.
Rigidity regarding optimal ranges has no place in combination therapy — “one size fits all” is the bane of T4 monotherapy, so let’s not let it creep into combo therapy. When websites like Stop the Thyroid Madness give guides to optimal Free T3 and Free T4 thyroid hormone levels and ratios, they can be very helpful up to a certain point, sure. But all these generalizations can be is a handy guide to where a lot of patients have reported feeling optimal. They are not absolute laws for each person.
Adjusting the FT3:FT4 ratio to optimize therapy
How much “net T3 supply” in blood is going to satisfy all your tissues and organs’ needs? What are your circulating hormone levels saying about your thyroid hormone metabolism?
Each individual, even in perfect thyroid gland health, will manifest a “fingerprint” range for their optimal — each person has a characteristic ratio of FT3 and FT4 in blood (See the science reviewed in “Individual thyroid ranges are far narrower than lab ranges“).
Optimal thyroid hormone levels ought to produce positive health outcomes. The ultimate goal is an absence of both hypothyroid and thyrotoxic symptoms. However, in real life, other disorders coexist with thyroid hormone disorders, so an optimal ratio would yield thyroid symptom-free living in the absence of other major illnesses, or would have the least severe symptoms in the midst of a chronic illness.
The “optimal” locations of FT3 and FT4 within or at the boundaries of reference range are always in relationship to each other. It never makes sense to judge FT3 or FT4 in isolation.
In thyroid therapy, it is necessary to look at bloodstream levels of thyroid hormone not just from the supply point of view (dosing & thyroid gland secretion), but from the perspective of the tissue consumers of hormone.
As a person’s T3 intake and T3:T4 ratio intake increases, one must permit their FT4 to drop to accommodate the T3, or you will overload them with “net T3 supply” in tissues.
On the other hand, if you lower T3 dosing, you will need more T4 in blood to deliver more T3 to cells within T4 “delivery packages” that provide slow-release tissue T3.
In combination therapy, T3 sufficiency is only obtained by flexibly adapting ratios and not fearing statistically-predetermined boundaries. The current paradigm fears and prohibits the crossing of reference range boundaries that often need to be the most flexible in T3-T4 combination therapy:
- Unnecessary Fear #1) The upper boundary of the Free T3 reference range (which is not hyperthyroid if FT4 is considerably lower),
- Unnecessary Fear #2) The lower boundary of the Free T4 reference range (which is not necessarily hypothyroid if Free T3 is considerably higher), and
- Unnecessary Fear #3) The lower boundary of the TSH range (which is not necessarily hyperthyroid if T3 dominates over T4 in a high T3:T4 ratio and both are within reason).
The abnormal dosing ratios and blood levels are not necessarily maladaptive. Abnormally low TSH and FT4 can also be therapeutically adaptive, as the next sections demonstrate.
Know about FT3 post dose peaks and valleys
When dosing any amount of T3 hormone, it is absolutely essential for both doctors and patients to understand the “curve” of FT3 in blood in relation to blood tests. It’s also useful to know the curve when splitting a dose 2 or 3 times a day for optimal symptom-free living. This section is a summary of a more extensive review in “Free T3 peaks and valleys in T3 and NDT therapy.”
The dosing curve strongly influences what your thyroid hormone-converting deiodinases and other metabolic processes are doing to T3 during its FT3 post-dose peak.
Time post-dose also tells you about how long FT3 takes to exchange with various organs and tissues and activate receptors to get a symptomatic response. If you experience a symptom within an hour after a dose, scientists suspect it is likely because of non-genomic FT3 action at the cell-membrane integrin αvβ3 receptors, not the more powerful genomic action at receptors in the nucleus.
Here’s a graph from Saravanan et al, 2007 that expresses changes in pmol/L and mU/L units. Notice the shape of the curve and where the average FT3 peak is located. Maybe you don’t want to dose 1x a day because this is quite a steep FT3 hill:
And here’s a graph that expresses it as % change in each hormone.
For dose-splitting advice and managing symptoms throughout each 24 hour cycle, learn from people on T3 monotherapy to understand how they live when they are fully exposed to the fluctuations of the fast-release (regular) T3 pharmaceutical. They don’t have T4 converting into T3 every minute of every day, so they feel the doses and the roller coaster, and they know what T3 dosing does to their body. You may find my T3 monotherapy narrative enlightening.
It’s rare for people taking T3 in doses NOT to split doses into 2x a day. If you are a slow metabolizer or are taking a lower dose ratio of T3:T4 you can get away with 1x a day, but as you increase total T3 dose, it will create higher peaks and you might want to dose more frequently to keep the peaks lower.
See the graph below from Ben-Shachar et al showing how you can cut down peaks during which your body responds more dramatically — especially in heart rate — and during which it more quickly clears out FT3. Each peak represents a dose.
As you multi-dose, you are taking less mcg in per dose and you are spreading out your FT3 levels between doses, economizing the $$ per microgram and being less demanding on your cardiovascular system and adrenals, and perhaps also your brain will thank you.
Be very consistent in blood test timing, always waiting the same amount of time after the FT3’s volatile and unpredictable “peak” in blood has faded, otherwise you can’t compare progress between two lab tests three months apart!
Measuring during peak FT3 is pointless, other than doing it once or twice out of curiosity or for research purposes. Even 20 minutes can make a big difference in FT3 levels during its volatile peak. The time it takes for FT3 to rise and fall from that peak is highly individualized and can shift based on D3 conversion activity that will likely be triggered at this time.
Lab testing FT3 consistently 12 hours post dose is a good rule of thumb because it is biased neither to the volatile peak, nor to the hypothyroid trough. Who wants to cause a patient undue suffering by delaying their next T3-containing dose too long? If most of a patient’s combination therapy is in the form of T3, starving the body of T3 for too long can have side effects afterward for days or weeks.
Know your three deiodinases
The three deiodinases convert our thyroid hormones in our cells. They are at the core of thyroid hormone metabolism.
They are the key to understanding how to help therapy fit an individual.
A doctor and patient dosing any combination of T3 and T4 should understand the basic science on the behavior of the two most prominent deiodinases in therapy, Deiodinase type 2 and type 3 (Learn about D1 further below).
Deiodinase type 2
This deiodinase is the most important for T4-T3 conversion.
It’s the deiodinase that has received by far the most scientific attention for this reason. Many of our articles discuss D2, and we can learn a lot from studying its role in any form of thyroid therapy.
The D2 enzyme is in almost every tissue, but it’s a fragile and vulnerable enzyme, sensitive to how much T4 is available to convert.
Understand ubiquitination — this is the process by which increasing Free T4 even within reference range causes T4 to yield less and less T3 in tissues.
To the same degree, lower Free T4 can optimize T4-T3 conversion — as long as T3 is not concurrently too high and triggering D3.
Few people discuss this fact, but D2 is also involved in converting T3 to one of its forms of T2, a benign and beneficial type.
Deiodinase Type 3
Deiodinase type 3, the fire-fighter enzyme that minimizes or prevents temporary thyrotoxicosis, can resurface within hours or days in any tissue where the body senses “excess” T4 or T3 above the current thyroid hormone homeostatic setpoint. Sometimes D3 goes a bit too far and runs amok de-iodinating more thyroid hormone than it should.
This D3 action is the real phenomenon that “Stop The Thyroid Madness” (STTM) — a valuable patient-driven resource for desiccated thyroid therapy — is talking about when it uses the language of “Reverse T3 dominance.” It’s actually Deiodinase Type 3 dominance, because D3 does more worrisome things than create Reverse T3 — it converts your T3 into T2.
STTM currently propose that RT3 is “blocking” nuclear receptors, something not possible given what we know of thyroid hormone action in cells.
Reverse T3’s more profound effect is that it amplifies Free T4 levels’ action of inhibits Deiodinase Type 2, without increasing TSH secretion (Cettour-Rose et al, 2005; Sabatino et al, 2015).
STTM also propose that the FT3 hormone is “pooling” in blood and unable to enter cells, which is just as highly doubtful in science. True pooling happens if you have an MTC8 deficiency — this occurs in rare males who are mentally retarded from birth because their brains don’t get enough T3 during fetal life (Bernal et al, 2015; van Mullem et al, 2016; Groeneweg et al, 2017). Yes, by describing “pooling,” they are describing a real phenomenon experienced by patients. Yes their tips may work for many people, since it is crowdsourced wisdom.
Understand D3 dominance and you will understand how to manage what is being described as “pooling” and what is really going on with both T3 and T4 when your RT3 levels are rising.
You can’t have any RT3 at all if you don’t have T4 to make it from, so of course RT3 will rise, even in a healthy person with a healthy thyroid, when their FT4 rises in reference. RT3 is not an evil molecule if healthy people make some every day.
Outside of thyroid therapy and fetal life, Deiodinase Type 3 is rather dormant, just operating enough to keep the body converting a flexible baseline percent of T4 into RT3 per day. This D3 enzyme gets powerfully upregulated and “reactivated” as D2 becomes suppressed (Bianco et al, 2019). This can occur when either or both FT4 or FT3 cross the upper boundary of an individual’s homeostatic set point (personal optimal range). The homeostatic ceiling can get lower during illness and this will reawaken D3 — after cardiac surgery, FT3 can plummet within 24 hours due to the quick response of D3, as it lowers the metabolic rate (Engler et al, 1978).
The generation of RT3 from T4 — and the generation of T2 from T3 — are simultaneous activities of the D3 enzyme in cells. It is one enzyme with two roles. There is a row of D3 “soldiers” in cells that express it (Bianco et al, 2019, Figure 1).
The main effect is that an overactive D3 leads to T3 hormone depletion. D3 can both destroy T3 or divert T4 into RT3 before those precious three-iodine molecules can reach the hormone receptor in the nucleus.
In thyroid therapy, there is a point at which D3 starts throwing micrograms of T3 and T4 medication in the metabolic garbage heap. The variant of 3’3′ T2 that is converted from T3 by this enzyme D3 can be thought of as “Reverse T2,” and one rare scientific article has called it that — Colucci et al, 2018.)
Deiodinase type 1
Deiodinase type 1 is a two-faced enzyme.
When FT4 is low and FT3 is below mid-reference, this enzyme can power-up the T4-T3 conversion that D2 enzyme is accomplishing. D1 also plays a role in increasing T3 oversupply in Graves’ hyperthyroidism.
But this enzyme can generate RT3 from T4 as well. Scientists don’t yet understand how or when D1 starts to switch over to remove iodine from the inner ring of the molecule where deactivation occurs, but they believe at normal levels of T3, about half D1 goes to T3 and the other half goes to RT3.
Deiodinase type 1 is powered by T3. It has thyroid response-elements (TREs), parts of thyroid receptors, in it (Gereben et al, 2008). This is one reason why it’s more efficient when T3 is relatively more abundant, and why it overpowers in Graves’ disease.
If you want RT3 to clear out of your body, D1 is your friend, because that’s its main job. If RT3 is building up, it’s not just because a lot of RT3 is being made, but it can be because D1 is downregulated or handicapped by loss of T3, and perhaps D1 is being overwhelmed by RT3 supply and can’t clear it out fast enough.
Deiodinase Type 1’s expression is localized mainly to the thyroid gland, liver, and kidney. These are the organs that are fast-exchanging with blood and generate a lot of blood FT3 via both deiodinases 1 and 2. A person without a thyroid loses a huge portion of potential D1 conversion activity.
Add to this knowledge of deiodinases an understanding of an individual’s metabolic handicaps so that you know how to optimize T4-T3 conversion in a poor converter on the one hand, and how to keep an eye on overconversion in a highly efficient converter of T4 hormone on the other hand.
The net effect of all three deiodinases
How do you know a person’s baseline conversion efficiency? The best measure of the degree to which a poor converter is truly handicapped is by doing the SPINA-Thyr analysis while they are on T4 monotherapy, not very sick, and FT4 levels are around 30% to mid range, where they would be in a normo-thyroid person.
Now consider how D2 and D3 can shift conversion to be less efficient or more efficient when FT4 and/or FT3 are relatively higher or lower in its range.
Now consider the individual’s metabolic handicaps.
The ultimate judge of the net effect is the person’s full body response to thyroid medication. At some point you have to go beyond blood levels and look at signs and symptoms.
Safe doses of T3 and NDT may suppress TSH
The abnormal behaviour of TSH in desiccated thyroid therapy (and other T3-dominant therapy combinations at different ratios) has become the biggest obstacle to its effective dosing and the more widespread application of desiccated thyroid therapy.
Too many doctors have a kneejerk reaction to a low TSH that is not justified by the older scientific literature that is the most informed about desiccated thyroid and synthetic T3.
What does our science say?
It says very clearly that TSH is a local tissue response. TSH is not a global indicator of T3 sufficiency all cells anywhere outside the hypothalamus and pituitary. TSH is not the secretion of an all-knowing godlike gland (Dietrich et al, 2012).
These two glands can be hypersensitive to factors beyond thyroid hormones because they are designed to drive change and anticipate metabolic needs, not just passively respond in a closed feedback loop, like some oversimplified models naively suggest.
With so many potentially competing inputs into these two glands, it’s not easy to adjust one hormone’s secretion, TSH. Thyroid tissue loss and thyroid therapy break down the natural feed-forward cycle and thyroid therapy interferes in the system’s normal function. (Hoermann et al, 2016)
What does thyroid science history say?
Robert Utiger, the renowned “father of the TSH test” had a few strong cautions against relying on TSH in T3-based therapy. See my “dialogue with Utiger” post for more details on his scientific experiments with T3 dosing, and his bold claim in 1972 that an effective, safe dose is one that is capable of suppressing the TSH.
As the TSH testing technology was developed between 1965 and 1988 and it became more and more sensitive to measuring small concentrations, levels below the normal statistical reference range, Utiger cautioned against the “overzealous” application of this lower TSH boundary to judge everyone below it as always thyrotoxic (Utiger, 1988).
Utiger had a prophetic sense of how the TSH test would grow too powerful and influential. He suspected that its sensitive lower boundary, the TSH innovation in the late 1980s, would be wielded against thyroid patients and could end up making thyroid testing less efficient and more costly in the long run.
Utiger’s own deep scientific research on desiccated thyroid as well as other therapies informed him as he wrote this passage cautioning overreliance on TSH mono-testing.
“Consider the problem of subclinical thyroid disease—that is, patients who are clinically euthyroid and have normal serum T4 and T3 concentrations but abnormal serum TSH concentrations.” … “These patients will likely undergo additional tests. In contrast, had only serum thyroxine [T4] been measured in such patients, the normal result would preclude the need for additional tests.”
Utiger continues: “In practice, much depends on the testing philosophy of those ordering the tests and the physician’s confidence in his clinical judgment…”
Ponder Utiger’s claim that “much depends on the testing philosophy” — it has become tyrannical and fanatical the more people yield their clinical judgment to a single pituitary number, the TSH.
“My conclusion,” Utiger writes, “is that the use of initial serum TSH measurements for evaluation of suspected thyroid disease has both strengths and weaknesses. It is clearly superior for assessment of certain patients, but as a general test in an ambulatory setting” [that is, outside of hospitals], “TSH measurements will identify too many patients in whom the unwary or overzealous may undertake unnecessary further testing and even treatment.”
Indeed the “overzealous” have taken on the job of guarding the lower boundary of the TSH reference range as if they were the holiest guardian angels of the thyroid church, protecting the immutable barrier between health and disease for all but a few exceptions (central hypothyroidism is a noteworthy exception — a handicap in TSH production).
However, it often means patients taking higher T3:T4 doses are forbidden admission to the realms of true euthyroidism.
Yes, when TSH is low or suppressed, that is often where patients find a healthy, optimal dose that produces reasonable net T3 supply in blood, finally satisfying all their tissues and organs (Busnardo, 1980).
A low TSH is the region where a significant percentage of T3-T4 combination therapy patients finally obtain T3 sufficiency and equality with their fellow citizens with healthy thyroids at a normal TSH.
Fear of thyrotoxicosis vs. hypothyroidism
Consider the built-in reference range discrimination that currently exists.
In thyroid therapy, one end of the TSH range is defended with more fear and zeal than the other, and it is invariably the lower end that is used to judge hyperthyroidism rather than hypothyroidism. That’s where the witch hunt happens.
How unfair is that?
To what degree is the lower TSH boundary harming patients who medically require a variable dose of T3 from their medication that, as a side effect, lowers or suppresses the TSH for reasons other than thyrotoxicosis (Goluart-Silva et al, 2011)?
To what degree is this ratio-limiting, TSH boundary-defending paradigm holding back understanding of natural human diversity in response to all thyroid therapy modalities, including T4 monotherapy?
Look at what happens at the other end of the TSH range, where overt hypothyroidism occurs. Criminal apathy and blindness to T3 sufficiency in tissues.
The dogmatists of thyroid therapy today are comfortable with allowing people to undergo the tortures of hypothyroidism for the rest of their lives.
They have not yet fully pondered the scientific findings on how unusual the “thyroid disabled” people are.
A thyroid patient’s Free T3 could be anywhere on the map at any level of TSH and Free T4. You can’t predict it!
This graph from Larisch et al (2018) shows the wide-ranging response of people with no thyroid gland to T4 monotherapy. The gray dots show where “healthy controls” are, in a limited region of the right hand side of the graph.
The main point is that we thyroid-disabled people are NOT like “normal” people with healthy thyroid glands.
As you can see, the TSH response to thyroid medication is NOT like the TSH response to hormones secreted by a living gland because it imbalances the hormones to different degrees in different people, and the TSH isn’t wired to interpret these ratio shifts.
With a TSH low or suppressed by medication, we may actually be euthyroid, or even underdosed, depending on our Free T4 and Free T3 levels and ratios in bloodstream.
Larisch and team’s work has been independently confirmed by a different set of researchers, Ito and team, through several experiments and articles (Ito et al, 2015, 2017 and 2019).
The general conclusion of this research tradition — even though it focuses on T4 monotherapy in thyroidless people — is that the TSH lower boundary is absolutely unfair to many thyroid patients.
It’s even more true in T3 therapy, since T3 dosing even at euthyroid, therapeutic doses, is well known to be a TSH-suppressant (Chopra et al, 1978).
The TSH cannot not accurately discern the point at which an individual patient becomes thyrotoxic.
Mild, temporary thyrotoxicosis
As you and your good, safety-minded thyroid doctor work together to discover your optimal FT3-FT4 zone, you might once or twice cross the line into mild thyrotoxicosis.
Occasional mild thyrotoxic effects in lifelong thyroid therapy are not unforgiveable sins. They are part of the trial and error of finding an individual’s true upper boundary for an optimal dose. If you don’t know where your upper ceiling is or how it feels when you get there, you don’t know where in your optimal range you are. This is fine tuning. Your thyroid used to be a self-driving car. Now you’re in the driver’s seat.
One must distinguish between true / overt hyperthyroidism and mild oversupply.
In hyperthyroidism, a patient with Graves’ disease has stimulating antibodies continually pushing a living thyroid gland to oversecrete both T3 and T4. That’s true hyperthyroidism. In Graves’ disease, an antibody attack forces on the body a continual oversupply of both thyroid hormones in blood.
True thyrotoxicosis leads to a continually elevated heart rate and continually higher body temperature day and night, not levels that fluctuate over 24 hours. (Mathur, 2018; Kalra et al, 2011 – see Wayne’s index for hyperthyroidism)
Patients can learn to read their own bodies over weeks, months, and years. We can learn from Paul Robinson’s books. We can learn from people who live on T3 alone — we can get to know these signs and symptoms as warnings.
Vital signs can be vital clues. Every thyroid patient who ingests T3 hormone should learn how to measure heart rate and body temperature and track them when making major changes in doses or fiddling with dose timing.
Not all cardiovascular symptoms are thyrotoxicosis signs. When the body falls low in T3 supply, it can give you surges of norepinephrine and cause episodes of tachycardia and palpitations. Hypothyroidism is associated with “impaired endothelial and nonendothelial-mediated vasodilation” (Napoli et al, 2007, 2010)
Be a mini-scientist and treat your body as an n=1 experiment. Plot resting heart rate on a chart or table, getting pre- and post-T3 / desiccated dose heart rate, at various times of day keeping in mind things like caffeine, exercise, ambient temperature, and meals. Take note of other symptoms like nervousness and mental health indices like cognition and emotions (Kalra et al, 2011).
Every thyroid patient can take their own body temperature (it’s a slower and more gradual response to T3 than heart rate) and plot it over time of day, and over the a menstrual cycle if they are female and pre-menopausal (body temperature reaches a low mid-month when estrogen rises and more thyroid hormones are bound than free).
Some people find that blood pressure is also an indicator — I personally have not found it relevant at all.
Poor sleep can be caused by running too low on T3 at night or by having too much T3 all night and keeping cortisol high. You don’t know which for sure, unless you get the right kind of cortisol test done. You can try taking a small dose of T3 when you have insomnia at 3am, for example. If it helps you get back to sleep within an hour, you have your answer, you were likely low on T3.
Fixing mild overtreatment
If you find yourself mildly thyrotoxic due to dosing, the fix is easy. You can change dosing now.
Usually the effects come from the peak Free T3 and/or Free T4 above a person’s built-in reference range — their own homeostatic set point’s ceiling.
Adjust ratios and doses down when the body speaks! You don’t need a doctor to write a new prescription to lower your dose immediately. What would your doctor want you to do? The answer is obvious. Don’t push your body when it is saying no.
How long does it take for T4 hormone to clear out, compared to T3 dosing?
The half life of T4 is a week at least, so let’s say 2 weeks at least to clear out most of the FT4 peak, but consider that the body hangs on longer to T4 the less it has, so there’s a long tail on the depletion of T4 (and RT3) that could take three months at the lowest end of low as it goes down the drain.
Consider that Total T3 has a half life of a day or two, but peak Free T3 has a far shorter half life, a mere 6-8 hours, after which is another long tail of gradual depletion.
Therefore, T3 dosing mistakes are more temporary in their effects and easier to fix.
How long will these thyrotoxic symptoms last if they occur — a mild tremor, a headache, a faster heart rate, and weak muscles?
Depending on how quickly those organs and tissues exchange 2-way with bloodstream Free T3 and Free T4, these symptoms could be as fleeting as a few hours, days, weeks, or a month until it is recognized and reported by the patient and resolved.
CONCLUSION: The human right to T3 sufficiency
Currently, the target of thyroid therapy is a huge range of normalized TSH discovered in people with healthy thyroids. Only the normalized TSH is the judge of effective therapy. This is a TSH secretion profile that is found in those with healthy thyroids who are not dosing any thyroid hormones.
Look in the research by Hoermann, Midgley, Dietrich and Larisch and you will discover that the HPT axis (our TSH, FT4, FT3 relationships) shifts profoundly away from “normal” in thyroid disease and therapy. Current guidelines do not adequately accommodate diversity of response to thyroid therapy. There are major flaws in our therapeutic paradigm.
Currently, official guidelines for thyroid therapy for the vast majority of patients limit them either to a nonphysiological rato of 0:100 T4 hormone only, or a tiny ratio of T3 to T4 micrograms in a rigid T3-T4 combination therapy modality.
The freedom to obtain global T3 hormone sufficiency in tissues is the birthright of every human being with a healthy thyroid. Have we lost our birthright with our thyroid function?
Shouldn’t a thyroid disability inspire a claim for for thyroid hormone disability rights and reference range accommodations, just like an ethical claim for the human right to mobility and accessibility aids, like ramps and railings, for those who have a mobility disability?
Why would anyone deny a patient the right to access “optimal net T3 supply” in blood by disallowing them from adapting the ratio of their T4 and T3 dosing, and/or adapting the ratio and levels of their Free T3 and Free T4 in blood, and/or forbidding a lower TSH or the non-secretion of TSH hormone?
Doctors and scientists, expand your door frames to allow disabled people through — expand your medical frameworks and paradigms. Make genuine tissue T3 sufficiency equally accessible to patients who need adaptive thyroid therapy.
Sincerely,
Tania S. Smith, Ph.D
President, Thyroid Patients Canada
and thyroid science analyst
REFERENCES
Click to view the reference list
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I absolutely love your research and your insight and am so very grateful for it. This website has been recommended to me by different sources as I was pleading for help with a T3 hovering around the bottom of the range (sometimes going below). Besides having very pour quality of life my body is now starting to pack it in (bones and kidneys and high cholesterol, so probably heart as well). I have tried everything I could get my hands on to raise my T3. It only goes up slightly if the T4 goes above range and the TSH below range (which is, of course, unacceptable to any doctor!). They say that knowledge is power but in this case the power is not mine. No physician here in Winnipeg, I have seen, has even tried to give me T3, even a tiny bit, to see whether it brings improvement. One endo even said that testing for T3 is a total waste of tax payers’ money and that T3 has no function. The rest of the doctors just adopts a “there-there-attitude” as if I were a stubborn child throwing a tantrum. If you know any physician I could see that would dare to put me on T3, just to see if it helps (instead of antidepressants and statins) I would so, so much appreciate it. I’m at the end of my rope for trying now over a decade to improve my situation. I hope you can help. Thanks for all you do.
Dear Elke, thanks so much for your kind comments. Sorry for the delayed reply, since I have been busy writing (and occupied with writer’s block, during seasonal T3 dose adjustments in spring).
Ah, sorry to hear that you too were forced to endure chronic low-normal / low T3 levels, just like I was, and it led to my having a major health crisis after 3 years, so there is a price to pay. You’re right, knowledge may be power, but we patients are powerless to test and prescribe. I’ve heard Winnipeg is a hard place to find a physician who understands the science on T3 hormone levels and T3 pharmaceuticals.
The responses you describe are examples of vitriolic pharmaceutical prejudice based on ignorance and a swaggering medical arrogance. I’ve seen flashes of this before, in my own experience as a patient. We are certainly not children, and this is cruel and insulting behavior. The way the ATA thyroid guidelines are written, it promotes this paternalistic and dismissive attitude toward thyroid patients’ genuine suffering. We patients must raise our voices publicly as a collective, armed with the science that they are ignoring, alongside the clear evidence that most of their own scientists have long been neglecting key longitudinal research on FT3 levels and health outcomes in treated thyroid patients.
Meanwhile, if you are seeking physician recommendations and peer support, I recommend our private support group on Facebook for patients only. Click the “groups” tab in the menu on our website.
– Your fellow thyroid warrior, Tania S. Smith
I have managed to find a Nurse Practitioner in Winnipeg who is willing to try things. She leaves a lot up to me since she feels that I have done my work and collected a lot of information. She provides me with the prescriptions and tests. So far so good. I’m cautiously optimistic now.
How would you deal with a sudden over sensitivty to T3 during & after menopause as related to sharply rising Follicle Stiumating Hormone (FSH) and corresponding increase in autonomic sympathetic activity?
Without going into detail. prior to menopause I was on mostly T3 with a little T4 with great results -hypo symotoms gone and a vast improvement with kidney function (I have chronic kidney disease). While my T3 labs were always elevated, my T4 was midrange and my RT3 towards the top end of range. I did not have hyperthyroid symptoms despite the out of range T3 levels – pulse normal, BP low-nomal, good heat and cold tolerance.
Perinanopause & Menopause my cortisol & adrenaline hormones became elevated – corresponding with a rise in Follicle Stimulating Hormone. My T3 levels almost tripled despite no change in wither T3 ot T4 dose. Both my T4 & RT3 levels dropped despite the increase in adrenal hormones. It was as if my body could no use the T3 medication, and instead was converting mostly T4 to obtain the required T3.
I switched to mostly T4 with a little T3 with good results with T3 levels being in range for the first time. For everything seemed fine -albeit with some weight gain and cold intolerance. I was able to lower the beta blocker but had to increase my BP medication-since while my pulse dropped, my blood pressure increased but with increased adrenal activity and sex hormone fluctuations I assumed those were factors since I had developed classic menopause vasomotor symptoms. MWhile I still had some adrenal response to T4, it was markedly less so than to T3 at this point. Having read that T3 elicits a higher sympathetic response-which reflects my recent sudden ‘T3 intolerance’ as menopause seems to have triggered sympathetic overactivity.
Six months later my FSH has almost tripled as my estrogen went from elevated to depressed. Correspondingly my sensitivity to T3 increased as did to T4. Despite doctor’s reassuring me that T4 could be taken any time, and having midrange T4 levels, I had to lower my T4 dose -along with my T3 dose. My autonomic -vasomotor symptoms have increased as has my sensitivity to both T3 & T4.
Any change in circadian rythm – sleeping in even an hour for example, or having a cup of tea- now seems to create a permnant increased adrenal response, resetting my pulse blood pressure point to a higher starting point. I still struggle to find even a stable dose of T4 & T3 as a result. A couple of cups of tea consumed a week ago, elevated my RT3 levels with accompanying symptoms that felt like the flu.
Conventional wisdom in treating elevated RT3 would be to lower T4 and add in more T3 yet I struggle to tolerate even a 2-3 mcg increase of T3 despite my T3 now being closer to midrange rather than the usual upper limits. Yet if I lower the T3, while my adrenal response decreases slightly, my RT3 contues to rise and the accompanying flu like symptoms also increase. Your articles seem to suggest that D3 enzyme is the culprit as opposed to just ‘elevated RT3 clogging cell receptors’ theory so would be interested to hear how apply this in my situation.
Do you have any insights on how to handle this sudden oversensitivty to T3 due to sympathetic overactivity and elevated FSH levels?
Thanks for an excellent site, really clarifies the intracellular process of thyroid hormone and conversion and accompanying issues.
Dear Mary, good question. You’ve been through a challenging time. Thanks for explaining the extreme changes that occurred with menopause, and your other conditions like chronic kidney disease. The synergy between these factors is very complex and individualized.
I recommend this new article on thyroid and sex hormones, even if it’s highly technical and scientific: Ren, B., & Zhu, Y. (2022). A New Perspective on Thyroid Hormones: Crosstalk with Reproductive Hormones in Females. International Journal of Molecular Sciences, 23(5), 2708. https://doi.org/10.3390/ijms23052708 — There’s a section in this article on the interactions between thyroid hormones (THs) and “FSH and LH” and another section on “GnRH”, the hormone that stimulates FSH and LH. They say that thyroid hormone signaling in general, most of which is done by T3, has variable effects on LH and FSH levels from person to person, study to study.
T3 certainly has the power to influence FSH secretion. In the other direction, FSH can increase TSH receptor (TSHR) signaling, so in this way it acts a bit like Graves’ disease antibodies do. You might have had a rare “FSH-secreting adenoma” on your pituitary gland secreting abnormal FSH. According to this article in 2021, “renal failure” could be an effect. https://www.frontiersin.org/articles/10.3389/fendo.2021.621456/ Based on the downstream effects of excess FSH on TSHR signaling, it seems logical it would enhance not only thyroidal T3 secretion but also T4-T3 conversion via D2 enzyme beyond the thyroid. Scientists have a lot of work to do to explain these things better in the future.
In the mean time, we have to work with our doctors, test what we can, and treat by FT3 and FT4 levels and their effects in our bodies. We can’t all follow “conventional wisdom” that gives advice on T3 and T4 dosing. That wisdom presumes your body is similar to the “average” patient, but your body is obviously not like other people’s bodies. I recommend joining our peer support group on Facebook (click “Groups” above) where unique people of all sorts can get some compassionate tips and support for their unique responses to thyroid hormone levels and dosing. Yes, we have seen some people intolerant of tiny doses of T3.
You didn’t mention your thyroid gland status. If you were hypothyroid due to TSH receptor blocking antibodies, remission and improved thyroid function can be extreme, and you could have had a mild TSH receptor stimulating antibody flare enhancing both T3 secretion and T4-T3 conversion. See our article on this website on “Remissions and fluctuations” in thyroid status.
Thank you so much for both the detailed reply and linked articles.
Regarding elevated FSH levels (esp. due to FSH secreting tumor) and renal failure, I came across a study that showed a higher incidence in renal impairment and failure amongst menopausal/post menopausal women. The study did not mention how many if any cases were tumor linked. I suspect that the culprit may be the increased FSH levels result in increased autonomic sympathetic activity which in turns increases adrenal hormones which when elevated, inhibit both thyroid hormone conversion (T4 to T3) and cellular thyroid hormone uptake. I also wonder how much the loss of hormones (inhibin A, B ect.)assocaited with the ovarian negetive feedback loop impact thyroid hormone function and uptake.
I am currenlty in the process of testing for Cushings disease *pitutary and adrenal tumors). My catecholimine levels are slightly elevated but not as dramatically elevated as in the case of an adrenal and/or pituatary tumor. My symptoms are accordingly only moderately elevated although enough to make even finding a daily dose of thyroid medication a challenge. I have not yet had imaging done so I appreciate your comments regarding the possibility of an FSH secreting tumor. I will discuss with my endo next visit.
I was initially diagned with mild hypothyroidism in my late 30’s, believe my T4 levels were normal but T3 mildly depressed. Not enough my doctor felt a tthe time to warrent any form of thyroid hormone replacement. I adon’t recall any testing for TSH receptor blocking antibodies…probably not I am guessing. In fact I had never even heard of such a thing until you mentioned it -so another subject to discuss with my current (much more thyroid informed) doctor.
Since posting my question, Imy doctor started me on menopause sex hormone therapy-initially testosterone and progesterone since my estrogen was extremely elevated. Estrogen was added shortly thereafter due to the levels falling once the t & p were started. Five months later we have discovered what appears to be severe progesterone intolerance in that even a small dose has a stimulatory effect on the adrenas glands resulting in a dramatic increase in both pulse and blood pressure, plus an inhibitory effect on thyroid hormone uptake. Apparently there are several mutations of either (or both) mineralcortisteroid and GABA receptos that can cause progesterone to have an atypical effect in causing an adrenal surge in some cases. There are different degrees of progesterone intolerance, some women only having PMs type symptoms with mild water retention to the more extreme casues like mine. Now I am only taking testosterone to bring my levels into normal range and so far doing much better. Progesterone does share some simlar properties as cortisol and is even being tested to treated conditions like carpal tunnel in lieu of using cortisone…so it seems not illogical that it could mimick excess cortisol in certain cases. I share this in case anyone else has expierenced a rise in BP, pulse, water retention, constipation along with a sudden inability to tolerate their thyroid medication. In my case my T4 adn T3 serum levels went up but I developed acute hypothyroid symomts including rapid weight gain (water retention), elevated BP and pulse, loss of energy, severe constipation and other symptoms that mimicked the effects elevated cortisol.
I have stopped T3 medicationall and am now on only T3. For the last 3 years my T3 levels have risen while my T4 (I was on mostly T3 with a little T4) levels suddenly plummetted. In essence it was as if my body was no longer using the T3 medication and instead using primarily the T4 medication…’preffering’ as tit were, to convert the T4 to create T3. I am at a loss to describe why this happened especially since this occured at a time of rapdily increase adrenal activity. Anyway a long and strange journey…never imagined that I would go from mostly T3 therapy to now only T4. For now the T4 only has resulted in a shar decline of cardiovascu;ar symptoms so much so that I will be able to go offer my beta blocker and lower my other BP meds. I share this just in case someone else hsa sudden;y developed a ‘T3 medication’ intolerance after being able to tolerate it well for years. Menopause seems to be the change that is the trigger.
Thanks again for your thoughtful and detailed reply. As my doctor said ‘we just aren’t there’ in regards to the full understanding of the endocrine system. Sites like yours however, help provide a much clearer pcture, particularily in regards to the intracellular processes involving thyroid hormone uptake. Thank you for your time and hard work.
Mary
I would like to get some feedback on this particular blog which appears to have some controversial viewpoints.
https://www.integrativeholistichealth.org/information/natural-dessicated-thyroid-ratio-t4-to-t3-causing-illness/
Bullet points made (true or false):
• cells close down admittance of T3 and T4 when the cells have reached their maximum capacity
• the ratio of T3 to T4 in NDT does not match the ratio we have in our human bodies. The T3 is way too high and causes resistance to occur
• a high reverse T3 demonstrates that there is either an inhibition of reverse T3 uptake into the cell and/or there is increased T4 to reverse T3 formation.
• A high reverse T3 can be associated with hyperthyroidism as the body tries to reduce cellular thyroid levels
• the free T3/reverse T3 ratio is proving to be the best physiologic marker of intracellular thyroid levels
• taking a compounded Thyroid medication, (not from a ‘natural’ animal source), in the ratio that is normal for humans may often be the best answer, that ratio being approx. 14:1 up to 19:1
Thank you so much for the work that you do. I am so overwhelmed and I have learned so much but still do not know how I should dose combination T4/T3? Is there a page that has a shorter explanation? For example if I am taking 70 mcg T4 and 5 mcg T3 how should I time the doses? Paul Robinson says to take the first T3 dose with the morning T4 dose then the second T3 dose in the afternoon. But I am not sure if this will work for me. How can I take this combination while trying to avoid the peaks and valleys of T3? I have tried combination T4/T3 many times in the past 2 years and I cannot find stability. But I know I desperately need T3. Thank you.
I had been on 100mcg T4 and was put on compounded, which did not work for me. Then 5mcg T3 was added to the 100mcg, which made the TSH plummet. It looked like T3 would be taken away from me again (after all, it looked like it was not working for me). So, I decided to go by the ratio of the compounded (approx.) and now take T4 50mcg 4x, 25mcg 3x per week and T3 5 mcg at 9am and 5mcg at 2pm daily. I feel fantastic. The only thing that bothers me is that the 25mcg pills are sooo much cheaper and I don’t know whether they are as impossible to split as the 5mcg. Otherwise, I would just split the 25mcg into quarters. There is a chart as to how to convert from T4 only to combination. Here is the link. I hope it helps. Best wishes. https://www.restartmed.com/thyroid-medication-dosage-chart/
thank you Elke this is very helpful I am so glad to hear you feel fantastic.
So you are saying originally your doctor gave you 100 µg T4 compounded with 5 µg T3?
I read the link you sent but I’m confused how you got to the amount in the end of taking approximately 40 mcg (average daily dose of T4) and 10 mcg T3 total daily dose?
Thank you for your help
Just trying to understand to make my own conversions… If you were taking 100 and 5 Cytomel compounded that is approx 120 mcg T4 equivalent? and now you are taking 80 mcg equivalent- Meaning 40 mcg average T4 and 10 mcg T3 = 80 mcg? Thank you for the help!
The Nurse Practitioner gave me exactly what the chart says in compounded; 38mcg T4, 9mcg T3 plus pro biotics to help with the slow-release absorption (I did not absorb…or so I was told after my TSH went to 23). Then she said to go back on the 100mcg per day again. With the TSH so high I decided to titrate to protect my organs. When my TSH was back to normal at 1,7 she added 5mcg to the 100mcg (which even then made little sense to me looking at the composition of the compounded). Then my TSH plummeted to 0.02 and I was told that I had to stop the T3. I discussed it with her and decided to get closest possible to the values of the compounded. My T4, T3 and TSH will be measured again at the end of the months. My NP felt that I could try this because she thinks I have amassed enough knowledge. Whether that is true or not I really don’t know. But that’s what I decided on and so far, it has paid off.
Maryam, I did not know how to answer to your replies directly. I hope this works and clarifies things.
Thank you so much Elke I think I’m understanding better!
Do you mind me asking if you still have a thyroid? I had a total thyroidectomy and for some reason I tried taking many different combinations of T4 and T3 the first year but I haven’t yet found a combination where I have felt stability. The most stability I have felt is with T4 only but I am still symptomatic. So I know I need to get more T3 somehow I just am trying to figure that out. I guess I’m one of those people that when I take T3 it’s like taking speed I’m super sensitive so it’s a lot of highs and lows and I end up feeling completely spent.
I still have a thyroid, but it is very small. The Hashimoto’s ate it all 😀
I’m sorry to hear that you tried so many things without having found just the right way to make you feel better. It really seems a hit or miss thing with thyroid issues (I have often heard the term “Goldilocks”). I also feel that the hormones are just one part of the puzzle. I’m on a forum called “Healthunlocked” where there is a group called “thyroiduk” and it is just mind boggling what works and does not work for different people. Some were helped by gluten free, some by upping their vitamin D intake, or B12 or folate. Some eat strictly plant based, low sugar, low fat others swear by organ meats and loads of coconut oil. This I find the most maddening part of all this, that you have to do all the work for yourself by yourself. It is, of course, great to be part of a group that will try to help as much as possible and give a number of tips and references to research. In the end, though, we need to figure out what is just right for us (and hope to find supportive medical staff to write prescriptions and requisitions, which in itself is a monumental task)). I’ve been at it for 50 years and still struggle along. And there are fantastic times and then the body decides that it’s time to try something new and you start looking for the right path again. And contrary to medical belief it is not just taking a pill and feel normal for many of us. Hang in there. Keep at it. Success comes from a succession of trials and errors. I surely wish you the very best in your quest.
Wow it really is a lot, I am so sorry you have suffered for so long. It really is criminal that the medical community is not up to speed so they can make a difference in peoples lives. I was reading the feed on this page and I saw that you had mentioned that even when you increased your dose of T4 so that it was above the normal range and your TSH was suppressed it did not raise T3?
I was just watching a video on YouTube with Paul Robinson and he was saying that if someone is able to raise their T4 dose and it increases their T3 that it would be OK to even go above the normal range for T4 and suppress TSH as long as the Free T3 increases (and they feel better)
I’m a little confused by that because I thought that if the free T4 was too high it could cause hyper thyroid symptoms. Maybe it’s different when a person doesn’t have a thyroid anymore? Bc with Graves if the Free T4 is higher than optimal that means there is higher than optimal T3 bc I had a working or overworking thyroid back then. Trying to gain some clarity about that because my T3 does increase when I raise my T4 however it’s at the upper third of the normal range right now and whenever I increase my T4 dose beyond what I am currently taking the hair loss increases. 🤷🏻♀️
But it’s interesting to know that you didn’t have hyper thyroid symptoms with higher than normal T4 and suppressed TSH.
Trying to wrap my head around this! I really am so very happy for you that you are finally getting to a better place. Best wishes for continued success and only feeling better and better!
That actually sounds like a really good plan. If I could split the tiny pill without pulverizing it taking T3 four times a day would probably be even better (albeit probably also a royal pain in the rear). I will keep the nibbling in mind, though. Thanks. 🙂
Yes, it is all very crazy. I have also heard that only if the T3 is above range hyperthyroidism sets in (regardless of T4 or TSH). I could not verify that claim (yet?). As for increasing T4 to increase T3, from what I understand some people just don’t convert the T4 into T3 very well. I assume that’s the case for me. So, I think that even if the doctors were better informed it would take too much effort and time, they don’t have, to figure things out for each individual because we are all different. It is just easiest to go by TSH and declare the patient soft in the head if they still have symptoms. I would not want to be a doctor under the current circumstances with patients flowing by like on a conveyer belt in a factory. Modern times. 😀
Yeah the nibbling thing is a major pain in the rear but if you’re feeling good with 5 µg twice a day I think that’s the most important thing – is feeling well. I guess the nibbling thing could get you out of a pinch where maybe I don’t know you were stressed out or traveling and you felt yourself dipping so you could just know that you can take a tiny bit more until you feel less symptomatic and you don’t have to take a whole tablet.
Wow OK every time I’ve asked my endocrinologist I feel like I’ve gotten different answers each time regarding if elevated T4 (without excess T3) can cause hyperthyroid symptoms. I will persist and ask again 🙄.
For me I know that I have tested as having one of the DIO1 polymorphisms and I sent off my test for the DIO2. I know I definitely have issues with not converting to T3 well enough bc I am quite symptomatic and my T3 has been at the rock bottom of the normal range on T4 only. But it appears that you may convert even less than someone like me?
My endocrinologist hasn’t suggested increasing my T4 because I think she’s concerned that it will suppress my TSH.
Once recently she told me I could increase it slightly because she said I had “room” to increase it and I asked her what that meant and she was vague and didn’t answer of course! But I realize now that she is concerned with suppressing TSH. I also learned today on another YouTube video with Dr. Bianco that T4 is a great suppressor of TSH but it is not an indicator of our cells having the T3 it needs. That was very validating to hear him say that.
Sorry one last thing 🤪 I just remembered that my reverse T3 was high … which is why I think I need to lower T4 and add T3 rather than increase T4. Paul Robinson says to get reverse T3 down
I just wanted to add that I also watched another video where one doctor said that the old school method of “time released“ T3 is basically nibbling on a tablet of Cytomel all day long 😕. The funny thing is I actually kind of started doing that I’ve been taking teeny tiny slivers like the size of a sesame seed every so often throughout the day and it helps I actually did that maybe an hour ago and that’s why I’m able to think clearly right now to type the message that I sent to you. It’s crazy!
I have a doctor who prescribes NDT (Erfa). But he got scared when my FT4 levels dropped low in range and prescribed levo to take with NDT. I felt good with a low-in-range FT4 and FT3 in the upper third of range but worse after adding levo to NDT…after reading your excellent articles, I think I know why.