THE THYROID GLAND MAKES THYROXINE (T4). and CALCITONIN, which lowers blood calcium. it also makes perhaps 10 – 20% of our T3, the active form of thyroid hormone.
Just as with DHEA, testosterone, estrogen, progesterone, Allopregnanolone and melatonin, there is a progressive reduction of T4 production by the thyroid as we age, which may result in true hypothyroidism.
Stress causes intracellular hypothyroidism by blocking triiodothyronine (T3) production.


T4 isn”t really a hormone: it’s raw material that TRIIODOTHYRONINE (T3), is made from.
T4 secreted by the thyroid gland is picked up by a protein called thyroid hormone binding globulin (TBG). More than 90% of T3 and T4 in the blood is attached to “TBG”.


Triiodothyronine (T3) increases the efficiency of all cells (including pituitary cells).

Where is T3 made?

The scientific literature contains many articles on the subject of thyroid hormones and the conversion of T4 to T3.
Some authors have suggested that T4 – T3 conversion occurs in the liver and kidneys only, but we now know that T3 production in the tissues: each cell takes some T4 from the blood, uses it to make T3 and passes any surplus T3 back into the bloodstream.

The “story” regarding thyroid hormone which I put forward below should be easy to read and understand.

Every cell makes T3, from T4.

Each cell uses a “Transporter” protein to import T4 from TBG and in the inner layer of the cell wall, an enzyme called Deiodinase 1 removes an Iodine atom from it, to make T3.
Most of the T3 only stays inside the cell for 20 minutes or so: it goes back through the cell wall and joins the pool of circulating thyroid hormone, by attaching to TBG.
Thus, the individual cell can import both T4 and/or T3 from the blood, without difficulty.

Thyroid function tests

In addition to testing for the thyroid stimulating hormone (TSH), we can test for the total amount of T4 and T3 in the blood, but testing for the portion which is “free” from TBG is more accurate, in terms of judging how much T3 and T4 is available to our cells.
The free T4 (F T4) tells us how much raw material is available to make T3.
The free T3 (F T3) gives an Idea of how much T3 is being made in the cells.


T4 is a protein molecule with 4 Iodine atoms. It is raw material (“prohormone”), for T3.
We have 3 “de-iodinase” enzymes (D1, D2, D3), which remove an Iodine atom from T4.
All the cells in the body and brain, except in the pituitary, use D1 to make T3, by removing the correct iodine atom from T4 (cells in the body and brain don’t have D2).
Cells in the pituitary gland don’t have D1: they use D2, to change T4 to T3.

T3 has a particular shape, which fits into “T3 receptors” * in all the cells, including those of the pituitary gland.
T3 receptors accept T3 molecules and when T3 plugs in, it increases cell efficiency. Without T3, the cells don’t work properly.

Deiodinase 3

D3 exists only in the body, including the brain: the pituitary gland does not have D3.
D3 removes a different Iodine atom, producing reverse T3 (rT3), instead of normal T3.
Reverse T3 is a different shape: it doesn’t fit into the T3 receptors and has no effect on cellular efficiency, but a blood test can tell us when a lot of rT3 is being made: if the cells are making too much rT3, we know that they are not making enough normal T3.

CATCH 22: Stress

When a human is subjected to stress – any stress, whether from high or low temperature, famine, natural disaster, animal attack, infection, poisoning, psychological strain or diseases like heart attack or stroke, cancer or any condition which disturbs normal function, every cell in the body reduces efficiency so as to save energy which may be needed for repairs.

This is how it works:
UNDER STRESS, cortisol is secreted by the adrenal glands, and ….
A: Cortisol blocks D1, but not D2, so no T3 can be made inside any cell, except the cells of the Pituitary gland!
B: Cortisol activates D3 and D3 removes the wrong iodine atom from T4, making “rT3”.
C: D3 also destroys any T3 present in the cell, by taking away one of its iodine atoms, to produce “T2”, which is completely inactive.
Thus cortisol removes T3 from all cells except the Pituitary, and all cells “hibernate”(except, of course, the pituitary cells).

The Pituitary doesn’t have the problem, because the It doesn’t have D1 or D3.
The Pituitary uses D2 to make T3, so it has enough T3 and it and puts out thyroid stimulating hormone (TSH) as usual, according to the amount of T4 it gets.
So when a human is stressed, the level of TSH in the blood tells the doctor that the Pituitary has enough T4, but does not indicate what is happening in the body.
If the doctor did tests to find out the T3 and rT3 level, the situation would be obvious. However up to now, doctors are specifically taught not to test for T3 or reverse T3.

Obviously, blocking T3 is a disaster

When you are under stress, there is little or no functioning T3 inside the cells, and all cells lose efficiency: in fact, the most sensitive ones shut down almost completely.
The result is lassitude, an overwhelming sense of tiredness and muscle weakness, reduced heat production with a feeling of being cold, “fuzzy thinking” with uncertainty and confusion, plus weight gain.
All of the symptoms tend to be worse in the afternoon and if the problem persists for long enough, chronic “low thyroid” symptoms” like dry skin, hoarseness, leg swelling, constipation, hives etc. can set in.

I call this stress-produced condition INTRACELLULAR HYPOTHYROIDISM. *
If it stays bad enough for long enough, it can progress to serious illness, which will be different from person-to-person depending on which of their cells and organs are most sensitive to the absence of T3.
As an example, see “Takotsubo cardiomyopathy“, a type of heart failure (“broken heart syndrome”) which happens to genetically predisposed people, when they are emotionally, or physically, stressed.
In particular, see a case report of cardiomyopathy, in my blog.
The incidence of Takotsubo Cardiomyopathy is between 2 and 10 cases per 100,000 hospital admissions, but there must be many cases of cardiomyopathy which are not recognized as “Takotsubo” and in any case, even the mildest cardiomyopathy should be suspected of being due to intracellular hypothyroidism.

* Also called “low T3 syndrome”, “functional hypothyroidism”and “nonthyroidal illness”, the syndrome is indistinguishable from “burnout”, “chronic fatigue syndrome” and “long Covid”, in terms of the symptoms it produces.

Recap: Details made simple

The thyroid gland lies in the neck, wrapped around the larynx (the voice-box).
It secretes all the T4 (about 90 to 100mcg daily) and 20% of the T3, for the body.
Every cell imports T4 and activates Deiodinase to make T3 out of it, using the T3 to maximise its efficiency.
Every cell exports surplus T3 into the bloodstream and we can test the blood for T3.
Remember: Pituitary cells use D #2, but all others use D #1, to convert T4 to T3.

T3 is responsible for 100% of the metabolic efficiency of all cells.
T3 helps to regulate body temperature, muscle power, body weight, glucose, cholesterol and everything else from hair and fingernail growth to mood and “well-being”: it controls every cell in the body and brain.

T3 is essential for the unborn baby’s brain development and the fetus does not begin to make its own T3 until the 14th week of pregnancy.
The baby’s brain connections are started between the 8th and the 14th week of pregnancy and If the mother is hypothyroid, or stressed enough to have intracellular hypothyroidism, while the “wiring” is being done, subtle abnormalities in brain growth may occur.
This can lead to cognitive and physical deficits in the newborn.
Autism spectrum, schizophrenia, dyslexia, ADD, obesity and gender dysphoria are all related to maternal hypothyroidism, but no one has thought about intracellular hypothyroidism being a cause.


Deiodinase 1 converts T4 into active T3 throughout the body.
Deiodinase 2 converts T4 into active T3 in the pituitary gland.
Deiodinase 3 converts T4 into rT3 and T3 into T2, in cells outside of the pituitary.
Deiodinase 3 does not exist in the pituitary.
D1 is blocked, preventing conversion of T4 to T3, when cortisol rises in response to physiologic or emotional stress.
D2 is not affected by cortisol.
D3 is activated by cortisol: as an energy-saving measure, it converts T4 into rT3 and any pre-existing T3, into T2.

The graphic below shows the process clearly: D3 removes the wrong iodine atom!
It was copied from “Cardiomyocyte-specific inactivation of thyroid hormone in pathologic ventricular hypertrophy: an adaptative response or part of the problem?”, by Christine J. Pol, Alice Muller, and Warner S. Simonides, in journal “Heart Fail Review, Nov 24, 2008).

Enzymatic metabolism of thyroxine: the enzymes – D1 & 2 make T3 from T4. 
D3 makes rT3 from T4 and T2 from T3.
blockade of D1 and the promotion of D3 resulted in intracellular hypothyroidism.
D1 (in the Body) and D2 (in the Pituitary) make T3 from T4. D3 makes reverse T3 from T4 and T2 from T3, BUT NOT IN THE PITUITARY, where no D3 exists.


(1) What is Deiodinase #3 USED FOR?
A: In either physical or psychological high-stress conditions, D3 SHUTS THE WHOLE BODY DOWN, SAVING ENERGY WHEN LIFE IS THREATENED.
(2) Under stress, does the pituitary gland shut down too?
A: No: in the Pituitary, D2 makes T3 and no rT3 is produced.
The pituitary is unaffected and the output of TSH continues, as usual.
A: With T3 formation stopped and available T3 converted to T2, the cells don’t have enough T3 to keep going.
(4) What does reverse T3 do?
A: Not much: we used to think that rT3 could hitch itself to the receptors and block the entry of T3, but really, all it does is to encourage the actions of D3.
However, rT3 is a perfect “marker” (a blood test signal) for intracellular hypothyroidism, because it only increases if the cells use D3 instead of D2 for T4 conversion.
(5) What are the symptoms of intracellular (“functional”) hypothyroidism?
A: The unfortunate human feels tired, weak, confused, anxious and depressed.
Any “low thyroid” symptoms (see the list below) can present themselves– for example:
The skeletal muscles don’t work properly and hurt, with effort.
Some people get muscle cramps.
Some get “Hoffman’s syndrome”, or “stiff person syndrome”, because the muscles can’t relax.
There is constipation: the “tight” bowel muscles can’t relax to let the stool go through.
There is cognitive loss, fuzzy thinking and confusion, due to of reduced brain function.
In some organs (varying from individual to individual), “subtotal” stoppage of function can occur (for example, heart muscle paralysis in Takotsubo Cardiomyopathy).
If the problem persists the fingernails get brittle, the hair (e.g. eyebrows) starts to fall out, there may be dry and itchy skin, the voice gets hoarse, the legs and eyelids swell from retained water, there is a feeling of being cold because the brown fat stops burning glucose, the cholesterol may rise, the body weight goes up and diabetes starts.
(6) If the problem is from insufficient T3, why doesn’t the doctor Prescribe T3?
A: The doctor tests “everything” except T3, T4 and rT3: the only thyroid test done is TSH, which stays normal because the Pituitary is “happy”.
So the Doctor can’t “read” the situation and doesn’t recognise the problem.
But in any case, the professors and the medical system tell the doctors specifically, that prescribing T3 is not good Medicine.
(7) So what does the doctor do to help the patient?
A: The MD may notice depression or confusion, high cholesterol, high blood pressure due to stress, muscle cramps, constipation, early diabetes, or swollen legs, etc.
So the sufferer gets a pill for each symptom.
(8) What’s the end result of intracellular hypothyroidism?
A: If the Stressful conditions come to an end, a “remission” may occur.
If the situation becomes chronic, serious disease, such as those above, may ensue: in the case of heart muscle weakness, there is heart failure and some people die.


Stress-related T3 deficiency, previously termed “Reverse T3 dominance”, is called “Functional Hypothyroidism” by the Metabolic Medicine community.
It is also called “Subclinical Hypothyroidism”, “Euthyroid Sick Syndrome” and “Nonthyroidal Illness Syndrome”, by mainstream medicine.
It is often confused with chronic fatigue syndrome (CFS).
It may be the background reason for “Long Covid” symptoms.
However the most appropriate term, in my opinion, is Intracellular Hypothyroidism (IH), because the real problem is insufficient T3 inside the cells.

In IH, testing shows (1) reduction of serum T3 from the individual’s usual level, to, or below, the low end of the “normal” T3 range and (2) Increased reverse T3 *, resulting in reduction of the T3/rT3 ratio.
TSH and T4 levels are normal, unless the patient also has true hypothyroidism.
The diagnosis is made if a reduction of the T3/rT3 ratio, to less than 20.0, is found. True hypothyroidism, with reduced production of T4, may coexist with IH. However in true hypothyroidism there is reduced, not increased, production of reverse T3.
Since some people are able to cover-up, or ignore, their low-thyroid symptoms, IH can sometimes be diagnosed on the basis of blood test results, even though the patient’s complaints are not typical.

Intracellular hypothyroidism is part of the pattern in all life-threatening illnesses.

It may be the result of the illness, or the cause of it.
It is found in the vast majority of chronic debilitating conditions, in prolonged depression and in morbid obesity, anorexia nervosa and starvation.
It is found after severe physical injury, major surgery, significant psychoshock and in acute illnesses severe enough for admission to intensive care units.
It is associated with heart failure, cardiomyopathy, Long Covid, PTSD, Chronic Fatigue Syndrome, ME, Fibromyalgia, the post-finasteride syndrome, infertility with recurrent abortion, major depression, schizophrenia and chronic true hypothyroidism.
It is also associated with neurological diseases, like MS, Parkinson’s disease, Alzheimer’s disease, Hoffman’s syndrome, stiff person syndrome and ALS.

Intracellular Hypothyroidism is pervasive, but is usually missed by doctors.
It can be “silent”, especially in confident people who have high self-esteem and tend to endure mild symptoms without complaint.
Therefore a “thyroid profile“, including TSH, T4, T3 and rT3 should be included in every “checkup” test series, regardless of the reason for the checkup.

Calculation, from the test results:
T3 is reported in Picomoles per litre (Pm/L) and rT3 is reported in nanograms per decilitre (ng/DL). to get the ratio, we first convert the T3 result to ng/DL.
Then we divide the T3 result in ng/DL) by the rT3 result: this gives us the “T3/rT3 ratio” **.
It should be >20 (the accepted normal), or ideally, >24.
Intracellular hypothyroidism is diagnosed if the ratio is <20.

Rating the severity of IH:
We rate the severity of intracellular hypothyroidism as follows:
7 – 10 = severe, 11 – 15 = moderate and 16 – 20 = mild.
If T3/rT3 is less than 21, treatment should be prescribed, to return the T3/rT3 ratio to >20
(>23 is better), by prescription of slow-release triiodothyronine, in addition to appropriate therapy for whatever other disease is diagnosed.

Treatment protocol: calculating the dosage of Triiodothyronine (T3).
“Cytomel”, a commercially available rapid-release triiodothyronine (T3) tablet, can be prescribed, but tends to cause a hyperthyroid “Spike” of serum T3 soon after it is taken and a T3 “Crash”, with recurrence of hypothyroidism symptoms, in the late afternoon.
Compounded T3, in a slow-release format, is preferred, because it does not produce a T3 spike or crash and the symptom relief persists throughout the day.
The prescription begins with 5 µg of triiodothyronine taken at, or close to, 4 AM.

Blood testing for T3 is done weekly * and based on the results the prescription is increased, if necessary, by 5 µg per day, until the serum T3 is >5 pmol/L.

When the T3 result is between 5 pmol /L, and 6.3 pmol/L, the prescription is continued without increasing the dose.
If a T3 test result of >6.2 pmol/L is reported, the dose should be reduced.
rT3 is not done along with the weekly T3 tests, for reasons of cost and convenience.*

* (1) Because the half-life of T4 is 6 or 7 days, it takes a long time to achieve a “balance” of T4 in the serum. Therefore it is necessary to wait 6 weeks from the date of a T4 prescription, to evaluate the effect of the T4 by blood testing.
T3 is quite different: the half-life is just a few hours, so the blood level produced by the prescription can be checked after 7 days.
(2) The diagnostic T3/rT3 ratio shows whether the abnormality of thyroid hormone metabolism needs to be corrected, but T3/rT3 is not a “target”, in terms of calculating the dosage of slow-release T3 for the individual patient.
(3) The serum T3 level is a better target: the dosage of slow-release triiodothyronine is increased until the serum T3 is between 5.0 and 6.2 pmol/L (see below).

T3/rT3 is checked every 3 months for one year: if it is >30, or consistently >20 for the full year, or If the T3 level exceeds 6.2 pmol/L , a smaller dose of triiodothyronine can be tried, “on spec”.
However the patient’s symptoms are more important than blood test results and for “perfect” physical and psychological function, some individuals need a T3 serum level at, or slightly over, the accepted upper limit.
Occasionally, if the stress can be completely eliminated, IH may go into remission: when this happens, it may be reasonable to discontinue T3 treatment. However a relapse to intracellular hypothyroidism is likely, if stress recurs.

(1) Please go to my blog on “NORMAL” and scroll down to the section re. the Thyroid.
(2) A T3/rT3 ratio table is available:… see below.


In the bloodstream, a “binding protein” (TBG) holds most of the T3, for a backup supply.
That portion of total T3 is inactive.
Therefore WE DON’T CHECK TOTAL T3: we check the “FREE”, UNBOUND T3.
In this website, references to “T3” always mean “Free T3” (FT3).

Calculating the FT3/rT3 ratio is simple in principle, but mystifying for those who aren’t mathematically inclined.
In Canada, the FT3 is reported in picomoles/litre of serum , while our T3 is reported in nanograms/DeciLitre.
To obtain the ratio, we must express both free T3 and rT3 in the same scale.
So we divide the FT3 value by 0.0154; eg, FT3 = 4.0 Pm/L /0.0154 = 259.74 Ng/DL.
We then divide the FT3 (Ng/DL) value by the rT3, to get the T3/rT3 ratio.

To continue the example, if T3 is 259.74 and rT3 is 15, the ratio is 259.74/15, = 17.3.
A T3/rT3 ratio of >20 is normal and >24 is excellent, while a ratio of <20 indicates preferential conversion of T4 to rT3 (instead of T3), severe enough to cause the signs and symptoms of intracellular hypothyroidism (IH).
So in this example our patient, whose FT3 is 4.0 pmol/L, and rT3 is 15, has moderate intracellular hypothyroidism and will benefit from treatment with slow-release triiodothyronine, from our compounding pharmacy.

The easy way to check T3/r T3 balance:

A table renders T3/rT3 calculation quick and easy: you only need to read the number at the intersection of the (horizontal) T3 row and the (vertical) rT3 column.

Cameron Sutherland’s T3/rT3 worksheet
by permission from Cameron Sutherland:

Quick calculation of FT3/rT3 ratio, from FT3 and rT3 test results

Table, for calculation of T3/rT3 ratio:
Light blue Column is FT3 values, in Pm/L.
Bright yellow Column is FT3 values, in Ng/DL.
Light blue numbers on the yellow row are rT3 values.
The FT3/rT3 ratio appears at the row/column intersections:
PINK area = normal range and WHITE area = Intracellular Hypothyroidism range.


IH is easily and safely treated with slow-release T3, but most doctors do not believe in, accept or even recognise the diagnosis and doctors are specifically instructed not to test for T3 or rT3 and not to prescribe T3.
They call IH “low T3 syndrome” and prescribe T4, expecting it to convert to T3.
This is disastrous: in IH, the underlying condition is the stress response, with increased cortisol production , so prescribed T4 is preferentially metabolised to rT3, making the situation worse because the rT3 helps cortisol to activate D3.
Most doctors are unfamiliar with Deiodiinase 3 and don’t believe patients who say that they get worse when they take T4: if the patient complains, they prescribe more T4.

HOW MUCH T3 does a person need?

Everyone has an individual requirement for T3, so we begin with a low dose and increase it sequentially, using weekly or two-weekly blood tests of serum T3, to determine when the correct dose has been reached. For purposes of titrating the dose of T3, we do not “need” to test either T4, or TSH.

Regarding TSH:

Most people’s “blood–brain barrier” (BBB) allows T3 to enter the brain and the pituitary.
When prescribed T3 raises the pituitary’s T3 level, the gland reduces TSH production to almost zero, and the thyroid responds by making less T4.
So most on-treatment blood tests show a higher T3, low-normal T4 and very low TSH.

However some people’s BBB blocks entry of T3 and then, if the pituitary’s T4 supply is down because the thyroid isn’t making enough, the pituitary puts the TSH up, to call for more T4. When this happens, tests show high TSH, low T4 and upper-normal T3.
This problem is insignificant. It is easily solved by adding a little T4 to the prescription.

Prescribing Desiccated Thyroid
Prescribing desiccated thyroid (DT) is an attractive idea, but DT is 70% T4 and 30% T3.
So taking it results in the patient getting a load of T4 along with their T3.
The T4 is immediately converted to reverse T3, which makes calculating T3/rT3 difficult.
Having said which, some people with mild IH do quite well on desiccated thyroid.


Spontaneous remission of functional hypothyroidism may follow stress relief, because preferential activation of Deiodinase #3 stops when the stress level and Cortisol output return to normal.
However most subjects promptly increase rT3 production and relapse into IH when a stressful situation arises.
The most spectacular example of remission and relapse of an intracellular hypothyroidism-based condition is found in cases of Takotsubo Cardiomyopathy.

After a while under prolonged stress and IH, the adrenals no longer respond with high cortisol production and cortisol tests may show low levels.*
Practitioners unfamiliar with deiodinase metabolism and IH can’t explain the low cortisol levels and the patient’s continuing complaints. They assume that the symptoms are due to low cortisol production, so they call the condition “Adrenal Fatigue”.
So, many ill effects caused by Functional Hypothyroidsm are blamed on “Adrenal Fatigue”, a fanciful label which is inappropriate.

We don’t know the mechanism of cortisol output reduction – there is nothing wrong with the adrenal glands.
The symptoms of Adrenal Fatigue are indistinguishable from those of IH, so perhaps the cause is simple:
Metabolic slowdown in IH affects the whole body except the Pituitary.
The adrenals are part of the body.
So if the adrenals respond to inadequate intracellular T3 in the same way as all our other cells, a reduction of efficiency and reduced cortisol production is unsurprising.
Therefore the failure of cortisol production in “Adrenal Fatigue” seen in IH may just be a previously unrecognised manifestation of Intracellular Hypothyroidism and nothing to do with the abilities of the Adrenal glands.

IF STRESS CAUSES IH BY INCREASING CORTISOL, why doesn’t the reduced cortisol in “adrenal fatigue” result in remission of IH?

Currently there is no answer to this question, but the symptoms of hypo cortisol is him are similar to those of hypothyroidism.

(1) Low T3, from true hypothyroidism or from IH, in women can cause infertility or abortion.
The foetus begins T4-to-T3 conversion for itself at approximately 12 weeks gestation and is not fully capable of making T4 until 20 weeks. Therefore If the mother is hypothyroid and a pregnancy persists, maternal T3 deficiency during the first 20 weeks may cause fetal hypothyroidism:
(2) Fetal hypothyroidism between 8 and 20 weeks of gestation can result in maldevelopment of the baby’s brain, with a variable degree of learning disability, gender dysphoria, ADD/ADHD, Autism, Schizophrenia and other neurocognitive states such as dyslexia, etc.

(3) Regarding Stress:
the origin of “stress”, whether “subjective”, “objective” or “id–perceived” may be psychoshock (including abuse), PTSD, life-threatening infections, severe injury, surgery and severe illness of whatever cause: it can be due to any disturbance of body or mind.
Even dieting, vitamin or mineral deficiencies, toxins or diseases can be the cause.
Basically, “whatever stresses you out”, physically or emotionally, can start the problem.

“Perceived stress” is stress subconsciously perceived by the brain, even if the individual claims to be stress-free, as super-confident people do.
Perceived stress, with or without subjective or objective stress, is present in close to 100% of ICU patients, causing IH, which can be proven by checking theT3/rT3 ratio.

“Subjective stress”
is consciously “felt” and can be described by the individual.  

“Objective stress”
is stress to, or on, the individual, as observed by others.

(3) Intracellular (“Functional”) hypothyroidism presents with recognised, or unrecognised, hypothyroid symptoms and signs, reduced T3 and high rT3.
IH can coexist with true hypothyroidism.
IH cannot be diagnosed with a TSH test: it is necessary to calculate the T3/rT3 ratio.
IH must not be treated with T4, because T4 will be converted into rT3, not T3.

(4) “Desiccated Thyroid” pills, made from dried porcine or bovine thyroids, consist of
30% T3 and 70% T4, bioidentical with the human hormones.
Human thyroid tissue contains 20% T3 and 80% T4, but the disparity is insignificant.
So, a person with IH, treated with Dessicated Thyroid, is getting genuine thyroid hormone, but the pills contain 70% T4, which Is converted into rT3.
treatment results are sometimes quite good; but the resulting flood of reverse T3 makes laboratory assessment of the patient’s condition difficult.
Further, once the IH resolves, the body begins to convert the T4 into T3 and excessive T3 production may result.

(5) TSH diagnoses true hypothyroid disease, but cannot be used to diagnose IH.
TSH is only relevant to the Pituitary’s satisfaction with its T4 supply.
TSH is not related to the body’s satisfaction with intracellular T3.
Intracellular T3 deficiency can only be assessed by estimating FT3/rT3.

(6) As thyroid function deteriorates and slows, so does the rest of the body.
Thus no system is exempt from the effects of Hypothyroidism.
It can make you fat, cause hair loss (check the outer 1/3 of the eyebrows) and dry skin. It can make your skin coarse and your voice hoarse.
Hypothyroidism can prevent bowel muscles from relaxing, causing constipation.
It can affect the eyes, tear glands (“dry eye”), long nerves (peripheral neuropathy), skeletal muscle (weakness, stiffness and muscle aches) (6) and heart muscle (7, 8).
It can cause leg swelling, or puffy eyes and face, from fluid retention.
It can cause numbness and tingling of the fingers.
It can cause brittle fingernails.
In the worst cases, atrial fibrillation, heart failure or dilated cardiomyopathy (7,8) may result from intracellular hypothyroidism.
Briefly put, Intracellular Hypothyroidism can cause almost any symptom you can name, because it can affect any organ: see the list of low-thyroid symptoms, below.

(7) Re. muscles and the heart, see Hoffmann’s syndrome and stiff person syndrome (effects on skeletal muscle) and cardiomyopathy (effect on heart muscle).
Also see: a case history, entitled “Hypothyroidism-induced reversible dilated cardiomyopathy” (this patient recovered when treated with T4, which in my opinion was lucky: she would have done better with T3)
and see my history (My own history of Intracellular Hypothyroidism).


T3 hormone is the efficiency factor for all body parts and the problems resulting from lowered T3 depend on which part of the individual’s body is most sensitive to lack of T3, so symptoms are many and varied.
Virtually any symptom may present, including those from Adrenal slowdown.
Many people with Hypothyroidism (either “true” hypothyroidism from underproduction of thyroid hormone, or “functional” (intracellular) hypothyroidism, with metabolic loss of T3 within the cells), report sluggishness, anxiety, “brain fog”, cognitive loss and a feeling of low energy, in addition to the classical hypothyroid complaints (see below).

SYMPTOMS short list
Low motivation
Depressed mood
Impaired memory
Poor sleep quality
Weight Gain
Reduced sex drive, male or female
Heavy or irregular “periods”
Recurrent abortion
Subtle abnormality of a baby’s brain development
Chronic yeast infections
Muscle weakness, including Myocardial weakness (see Ref # 6,7,8).
Muscle aches
Joint Pain, stiffness, swelling
Difficulty staying warm
Difficulty breathing
Slower heart rate
Puffy face, Dry skin, Acne
Brittle hair and nails
Calloused heels
Premature gray hair  
Brittle fingernails
SIGNS noticed by the doctor
Slow pulse, Irregular pulse, Low BP,
Temperature < 36°C
Dry skin + Dry hair / grey hair
Heel calluses
Hair loss from the head, legs or eyebrows (outer 1/3)
Swelling below lower eyelids
Skin swelling over the shins
Hoarse, “thick” speech,
Dry cough
Slow thinking, confusion
Memory loss,
Home in endemic area
Economic disadvantage
History suggesting FH
High-stress job,
High-stress job partner
High-stress life partner
Separation, divorce
(Parents): difficult children
(Children): difficult parents
Childhood abuse of whatever type
Chronic illness, eg.
Celiac Disease or gluten intolerance
Severe illness, with ongoing anxiety
Difficult life circumstances
Dependent relatives
Anxious personality disorder
Other psychopathy, schizophrenia and “bipolar disease”
Family history of hypothyroidism
Retirement, social isolation
Alcohol / tobacco / THC /drug habit
1:   Iodine deficiency
2:   Selenium deficiency
3:   Hashimoto’s thyroiditis
4:   Ionising radiation
5:   Therapeutic radiation
6:   Thyroid/ Pituitary Surgery
7: Unknown cause
8:   Prescribed medication
9:   Stress (IH)
10: Worse IH with Eltroxin *
11: Hypopituitarism 
Elevated blood cholesterol level
Borderline blood sugar/A1C
High TSH, with or without low T4
Low T3, High reverse T3, Low FT3/rT3 ratio, with or without high TSH
“Adrenal Fatigue”
Low DHEA, Testosterone, Oestrogen, Progesterone, Allopregnanolone
Fluid retention, with or without heart failure  
Iodine &/or Selenium deficiency
HEAVY METAL OVERLOAD CAN CAUSE SIMILAR SYMPTOMS: the Urine should be checked for Heavy Metal “burden”
Eltroxin*, plus iodine and/or selenium, for # 1 – 8.
Compounded, slow-release T3, for # 9, 10 & 11.
Selenium (2 Brazil nuts per day will provide enough).
Iodine (2 drops of Lugol’s iodine per day).
Iron: serum iron (“Ferritin”) should be kept >100.
DHEA, 50mg/day (men) and 25-50mg/day (women) reduces symptoms.
* Eltroxin makes #9 MUCH worse.
CONDITIONS ASSOCIATED WITH Intracellular Hypothroidism
Long-COVID syndrome,
CFS/FM, Gulf war syndrome, PTSD (CHILDHOOD or ADULT), Depression,
Lyme Disease,
Menopause, Psychiatric conditions, autism, Type I or II Diabetes, obesity, peripheral neuropathy, Alzheimer’s, Autoimmune diseases (rheum. arthritis, lupus, sarcoidosis, Sjogren’s, etc.),
Fibrillation, heart failure, Takotsubo Cardiomyopathy,
Adrenal Fatigue,
Crohn’s disease, Ulcerative colitis, Diverticulitis,
Heavy-metal overload,
Multiple sclerosis (MS), Hypercholesterolaemia, Heart failure,
Chronic anxiety/depression, Schizophrenia
ALL TYPES OF SEVERE ILLNESS, or admission to an ICU.

If you think the above list is fanciful, please read my own history of FH in the blog post, ON THE SUBJECT OF FIBROMYALGIA“, for the whole story.


(1) Trans Am Clin Climatol, 2013;124:26-35, Cracking the code for thyroid hormone signaling: Antonio C Bianco 1 PMID: 23874007, PMCID: PMC3715916
(2) Endocrinology, 2021 Aug 1;162(8):bqab059. doi: 10.1210/endocr/bqab059.Deiodinases and the Metabolic Code for Thyroid Hormone Action, Samuel C Russo 1 Federico Salas-Lucia 1 Antonio C Bianco 1 PMID: 33720335, PMCID: PMC8237994 (available on 2022-03-15),
DOI: 10.1210/endocr/bqab059
(3) Endocr Rev. 2019 Aug 1; 40(4):1000-1047. doi: 10.1210/er.2018-00275. Paradigms of Dynamic Control of Thyroid Hormone Signaling, Antonio C Bianco 1 Alexandra Dumitrescu 1 Balázs Gereben 2 Miriam O Ribeiro 3 Tatiana L Fonseca 1 Gustavo W Fernandes 1 Barbara M L C Bocco 1 , PMID: 31033998, PMCID: PMC6596318, DOI: 10.1210/er.2018-00275
(5) Clinical Endocrin., Volume81, Issue5, Review, November 2014, Pages 633-641: Defending plasma T3 is a biological priority Sherine M. Abdalla, Antonio C. Bianco: 05 July 2014
(6) Hoffman’s syndrome – A rare facet of hypothyroid myopathy, Swayamsidha Mangaraj and Ganeswar Sethy, Neurosci Rural Pract. 2014 Oct-Dec; 5(4): 447–448. doi: 10.4103/0976-3147.140025PMCID: PMC4173264PMID: 25288869
(7) Hypothyroidism-induced reversible dilated cardiomyopathy, by P Rastogi, A Dua, S Attri, and H Sharma, J Postgrad Med. 2018 Jul-Sep; 64(3): 177–179. doi: 10.4103/jpgm.JPGM_154_17
(8) Myocardial Induction of Type 3 Deiodinase in Dilated Cardiomyopathy (experimental, Mice), Ari J. Wassner,1Rebecca H. Jugo,1David M. Dorfman,2Robert F. Padera,2Michelle A. Maynard,1Ann M. Zavacki,3Patrick Y. Jay,4 and Stephen A. Huang1 Thyroid. 2017 May 1; 27(5): 732–737. Published online 2017 May 1. doi: 10.1089/thy.2016.0570PMCID: PMC5421592PMID: 28314380
(9) Thyroid Hormone Transport into Cellular Tissue, Journal of Restorative Medicine 3(1):53-68, April 2014, DOI:10.14200/jrm.2014.3.0104, by Kent Holtorf, Holtorf Medical Group (HMG),I can supply further references, on request.
(10) “Stiff person syndrome” –
(11) Attention deficit hyperactivity disorder and autism spectrum disorder in children born to mothers with thyroid dysfunction: a Danish nationwide cohort study, by
S L Andersen  1 P LaurbergC S WuJ Olsen,
PMID: 24605987, DOI: 10.1111/1471-0528.12681

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