Understanding the difference between true hypothyroidism and the low T3 syndrome
My main interest is hypothyroidism and in particular, the Low T3 Syndrome, which I refer to as Intracellular Hypothyroidism.
I began this post with the intent to express my opinion on the subject of restless-leg syndrome, which is associated with hypothyroidism; but perusal of the available literature on the subject led me back to the realisation that of all medical subjects, thyroid function is most discussed and least well understood .
Understanding true, versus intracellular, hypothyroidism The limiting factor in any discussion of thyroid function is the breadth of vision of the debaters.
There is generalised, blind acceptance of the premise that thyroid stimulating hormone (TSH) is the be-all and end-all of thyroid function investigation: because of that, the levels of T3 and reverse T3 are ignored. This stumbling block is an impediment to an understanding of all hypothyroid conditions, from hives to “brain fog” from fatigue to heart failure, in which thyroid hormone levels play a part. So what I would like to do in this post is to make one more attempt to get my readers thinking in a more logical fashion, about thyroid function, hypothyroidism and in particular, the Low T3 Syndrome.
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All PD patients in this study had intracellular hypothyroidism
Doggone LowT3 Ssyndrome! Parkinson’s by itself is bad enough!
Parkinson’s and the thyroid
A recent communiqué, delivered to my newsfeed, made reference to an interesting paper in Clin Exp Immunol, 2022 May 3;208(3):372–379. doi: 10.1093/cei/uxac044 . Entitled “Genetic correlation between thyroid hormones and Parkinson’s disease” and submitted by Jiyi Xu1,2,#, Cheng Zhao3,#, Ye Liu4, Congjie Xu5,6, Bin Qin7, Hui Liang (PMCID: PMC9226140 PMID: 35511827).
The abstract reads as follows (paraphrased): “Parkinson’s disease (PD) is a progressive neurodegenerative disease, characterized by tremor, bradykinesia, myotonia, and non-motor symptoms. Clinically, degeneration of dopaminergic neurons in the substantia nigra, α-synuclein deposition, and Lewy body formation are characteristic pathological changes.
With the aging of society, the incidence of PD is increasing, but the pathogenesis is still unknown*. Dysfunction of the immune system is considered to be a critical cause of PD and has received increasing attention in the past decade.
An epidemiological study in Sweden (2023), involving more than 300 000 subjects, showed that patients with autoimmune diseases, such as amyotrophic lateral sclerosis, Graves’ Disease/Hyperthyroidism, Hashimoto’s Thyroiditis/hypothyroidism, multiple sclerosis, and rheumatoid myalgia, had an additional 33% risk of PD.”
* I would like to know whether stress, with low T3, close-to-zero DHEA and testosterone, plus deficiencies of pregnenolone, melatonin, magnesium, sulphur, Iodine, Selenium etc has anything to do with neurodegeneration, but no-one else seems to think in those terms!
A well written paper; but they entirely missed the significance of rT3!
The authors felt that the known correlation between thyroid function and PD was worth exploring and particularly, they wondered whether a genetic susceptibility to “autoimmune” disease might affect both the nervous system and thyroid function.
Therefore they undertook a study, aiming to answer two questions: (1) whether there is a difference in thyroid hormone levels between PD and healthy controls and (2) whether PD-related genes affect thyroid hormone levels. They investigated a group of Parkinson’s Disease patients, comparing them with matched controls, with emphasis on the effect of 12 different SNP’s on the patient’s thyroid hormone.
Examining the genetic correlation between thyroid hormone function and PD, so as to analyse the effect of PD-risk genes on thyroid function, they found 12 “meaningful SNP’s” which could affect PD and thyroid function through an immune mechanism and discovered that thyroid function indices between PD and their control group were significantly different.
The study was very well designed and the comparisons between the 12 different groups were meticulously recorded, utilizing tables, of which I have copied one (below).
The object of this post
I have little interest in the authors’ prime concern, as to whether or not PD and thyroid disease are linked according to genetic characteristics. However I find their detailed analysis of the thyroid hormone parameters fascinating, revealing and hugely important to our understanding of hypothyroidism in general and Intracellular Hypothyroidism in particular: this is the first time that I have seen such a detailed list of thyroid tests, including reverse T3 (rT3), which is usually ignored!
I’m also interested in a segue, from Parkinson’s disease to myocardial failure: more on that, below; for now, let’s look at their tables:
Incredibly detailed thyroid function tables
Table 1 summarizes the characteristics and thyroid function indexes of participants. Comparing all eight indices of thyroid function (TT4, TT3, TSH, FT3, FT4, TPOAb, TGAb, and rT3)in the two groups, it was found that the levels of TT3, FT3, FT4, and TSH in the PD group were significantly lower than those in the control group, while rT3 was significantly higher than that in the control group.
Table 1: – Note that normally, FT3 is between 2.3 & 4.2 Picograms per ml (3.2 to 6.2 Pmol per Litre. Thus the PD subjects actually did not have suppressed serum FT3 levels. – However rT3, which should be less than 13 (see aT3/rT3 table, below table 1), ranged between 50 and 63 Ng/DL: this very high rT3 level,, common to all of the PD subjects under investigation, indicates that 100% of the patients had severe low T3 syndrome (defined as T3/RT 3 = <20).
Normally, FT3 is 2.3-4.2 Pg/ml (3.2 to 6.2 Pmol per Litre. rT3 should be < 13
This finding is repeated, with numbers very close to these, in all 13 of the tables presented in the article: I won’t bore you by copying the subsequent 12 tables, to this page!
The unusual FT3 (2.9 – 3.44 Pg/mL) and rT3 (48 – 63.28 Ng/DL) values are similar, in all 13 tables.
Note that Normal FT4 in adults is 0.8 to 1.8 ng/dL
No mention is made in the article, of iodine, selenium, magnesium or any other essential minerals, vitamins, amino acids or other nutrients and neither is mention made of hormones (DHEA, cortisol and the like), diet, lifestyle habits or exposure to heavy metals and other toxins, which might affect thyroid function will will will will.
The bottom line
There are two conclusions from table 1: (1) The figures for all parameters, between patients and controls are not hugely different, including the reverse T3 levels, while the average rT3 among patients was 58, the average among the controls was 48: therefore the controls also had the Low T3 syndrome.– Please go to “hypothyroidism diagnosis” and read “Basic facts and the bottom line”– if the rT3 exceeds 20, T3/rT3 must be less than 20, unless the patient is hyperthyroid.
(2) The best free T3 level, 3.44 pg/mL, translates to 5.28 picomoles per litre and the worst, 3.01, is 4.62 pmol/L: both are normal, on the Ontario scale of 3.2 – 6.2. all the numbers you a T3/rT3 ratio of less than 10, indicating severe intracellular hypothyroidism.
These facts however do not change my conclusion, as stated below.
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There is now general consensus, that Micro–Thrombotic injuries from Covid’s Spike Protein persist for at least 6-15 months after Covid infection (or vaccination) and constitute a possible cause of long COVID symptoms. This is supported by, among others, an article in “Cureus”, of 2023 Nov 21;15(11):e49204, by Nicolas Hulscher1,✉, Brian C Procter2, Cade Wynn2, Peter A McCullough3,4 , entitled “Clinical Approach to Post-acute Sequelae After COVID-19 Infection and Vaccination” (doi 10.7759/cureus.49204).
The abstract reads (paraphrased) as follows: “The Spike Protein of SARS-CoV-2 is a cause of sequelae after SARS-CoV-2 infection or COVID-19 vaccination. The vaccines utilise a modified Spike Protein with toxic effects similar to the virus itself: there is abundant evidence that the Spike Protein, whether from SARS-CoV-2 itself or from vaccination, causes inflammatory damage to the cardiovascular, hematological, neurological, respiratory, gastrointestinal, and immunological systems, by means of producing micro-clots in the capillaries.“
The obvious questions
Vexing questions arise: (1) are the symptoms of long Covid purely products of micro-thrombosis caused by spike protein, or are they partially the product of stress, as perceived by the hypothalamus. (2) What can be done to prevent “Spike Protein” activity?
The incidence of DHEA deficiency in a family practice: symptoms observed and the effects of supplementing serum DHEAS
FIRST, THREE CAVEATS
(1) Please allow me, before going any further, to recognise and admit that this is an anecdotal, retrospective report, regarding an unfiltered, un-organized population which attended a family practice ad hoc, between 2006 and 2021, at the time, there was no plan to report the findings and no control of time of presentation. Particularly, this was not a double-blind study. This report therefore, is presented as an opinion piece, which (hopefully), some scientifically-inclined researcher may find thought-provoking and worthy of in-depth, scientific investigation. (2) Some of the graphics herein were taken from previous publishings and their enumeration may seem inappropriate: please consider correct., the enumeration in the text. (3) I report on 585 individuals – 266 men and 359 women, but this post shares detail regarding the men only – the women’s symptomatology was very complicated and would have rendered this article much too long: their stories will be reported in a separate post, in July, 2025.
Fig 1: Genesis and metabolism of DHEA
Fig 1: Processing Cholesterol, to produce human Neuroactive Steroids
585 documented patients: 226 males and 359 females
I have analysed the records of 585 patients, to the point of detailing my therapeutic success in the management of 226 males; but the 359 female patients’ records are so much more complicated that my report re. therapeutic success with women cannot be readied for some months: I will complete it by mid-July 2025 and will submit it as a stand-alone post.
No concrete conclusions can be drawn from this record, regarding any aspect of DHEA deficiency, excepting for the salient points ……..
A sufficiently large subset of the patient population (in my family practice, 92% of females and 70% of males) needs investigation for DHEA insufficiency, to warrant advising family physicians to be aware of the problem and to prepare to diagnose and treat the condition.
Health Canada’s attitude toward hormone restoration in general and DHEA/Pregnenolone supplementation in particular, needs to change! It is time to remove these two side-effect free, supportive, all-important antiaging hormones, which have been freely available over-the-counter in the United States since 1995, from Canada’s “dangerous drugs” list.
At a minimum, we should educate our family practitioners on the subject of DHEA and DHEA deficiency and we should permit them to recommended supplementation appropriately.
At best, Canada should permit over-the-counter sales of DHEA and Pregnenolone: the result would be ASTRONOMICAL SAVINGS, for our publicly-funded healthcare system.
Background review
DHEA is a fat-soluble molecule, which you might call a “steroid ring”. It is produced in small amounts by the brains of all animals and in large amounts (more than all of our other hormones, put together) by the adrenal glands of the primates, including humans. It is the essential raw-material for production of neurosteroid hormones and its deficiency implies deficiency of Its “downstream products” (Fig. 1).
Fig 2: DHEA, the prime Neurosteroid prohormone: the “mother of Testosterone”,
The active form of DHEA (Fig 2) is fat-soluble, but for transport in the blood, a sulphur atom is attached to it, producing water-soluble “DHEAS”.
Adding the sulphate (Red and yellow, left, lets DHEA (+S) dissolve in water
DHEAS is delivered via the blood, to all cells in the body: on entering the cells, the Sulphur atom is removed and the molecule reverts to fat-soluble DHEA.
Within the cells, DHEA is modified, to produce Testosterone and a series of “micro-hormones”, different for each cell type, which each produces for its own use. Thus DHEA is not truly a “hormone”, because apart from its special action (blocking an enzyme called G6PD) to promote the death of cancer cells, it doesn’t make any changes by itself: it is simply raw material for neurosteroid * hormone production.
DHEA levels are high at birth, because the mother produces it in quantity during pregnancy and it crosses the placenta to the baby. Levels fall rapidly after birth and remain low until puberty: at “Menarche” (girls) or “Adrenarche”(boys), between age 8 and 13 years, both genders maximise DHEA production (Fig. 3), keeping it high until age 25.
* “Neurosteroids” are hormones which are active in the brain and nerves.
Fig 3: Graphic from the excellent website, “you and your hormones”: Normal serum levels of DHEAS (red line), during pregnancy and up to age 20 – the curve for cortisol is included, because DHEA and Cortisol share the “root”, Pregnenolone (Fig1) The graphic shows DHEA in the male: in the female, DHEA levels are lower, but the trend is the same.
Fig 3: Male Serum DHEA and Cortisol, from pregnancy, through age 20
What DHEA does, for Humans
As the “prohormone” raw material for the neurosteroid hormones our cells (in particular, our brain cells) need, DHEA helps to keep function normal in all our organs. But starting at age 26, both men and women reduce production of this all-important prohormone, by 1% per year. So by the time we get to age 80, the production of DHEA is down to 10 % or less of what it was at 20 and eventually, the blood level hits Zero.
The basic cause of aging
This reduction of available DHEA is the root cause of many health complaints and is the basic cause of “aging”: the incidence of noncommunicable disease, including cancer, rises as DHEA fades away (see Figure 5).
The progressive loss of DHEA production and the gender difference are nicely documented by the “Normal DHEA” table with which test results were reported by “Life Labs”, in Canada, early in the 21st century – see Figure 4 and the associated “normal” table, below:
Fig 4: DHEA levels, and DHEA in pm/Litre, by age, according to “LifeLabs” (1) At puberty, the male surge of DHEA production is greater than the female’s (2) These “Normals” are verbatim, from LifeLabs: “male, age 13–23” must have been a typographical error – I assume that it should have been “<14.0”
The 1%-per-annum diminution of DHEA production occurs in both sexes and begins at age 25. The rate of loss It is the same, regardless of the DHEA level at age 25 (the level at 25 is variable, because those who were stressed as children, or in the teen years, tend to produce less DHEA). Note that women, who have lower serum levels in youth, tend to become deficient at an earlier age.
DHEA deficiency
When the serum level falls below 6.0 pmol per litre, symptoms of DHEA deficiency begin. Usually, women’s DHEA level falls to less than 6.0 micromoles per Litre at some point between 30 and 40 years of age, while men usually don’t cross that threshold until they are over 50………Howeverunder stress conditions (especially in cases of childhood PTSD), aberrations of function due to subnormal DHEA supply can begin in the teen years.
The effect of childhood PTSD
When stress causes PTSD in childhood, Pregnenolone is “stolen”, to produce Cortisol instead of DHEA.
But that’s not all – not only is DHEA suppressed; cortisol decimates T3 production inside the cells, so the unfortunate child enters the teen years in a self-perpetuating state of combined DHEA deficiency and Intracellular Hypothyroidism.
Fig 5: PTSD hobbles DHEA* and serum DHEA <6.0 can occur in the teens.
Figure 5:My clumsy modification of J.W. Nyce’s superb graphic showsthe effect of PTSD on DHEA production. The blue (Male) and blue-green (Female) lines show humans’ DHEA level with age: Women’s levels fall below 6.0 by age 35-40, but Men’s DHEAS levels may exceed 6 pmol/L through age 60. The “lesser”, long-lived animals, producing DHEA only in the brain, have low, but steady, DHEA levels (purple line). The red line shows our risk of cancer and other noncommunicable diseases, while the green one shows the liability to degenerative disease of long-lived mammals, who use other factors for protection from NCD’s. The black line (my modification) shows the effect of childhood PTSD: serum DHEAS is reduced to less than 6 pmol/L by age 30 or earlier, and occasionally, in both girls and boys, may not even rise to 6.0 Pmol/L during the 2nd and 3rd decades.
DHEA deficiency
According to popular legend, as promulgated by our putative medical cognoscenti, the decline of DHEAS in our serum (Figures 4 and 5) is natural and therefore, the gradual disappearance of DHEA from our bodies constitutes neither deficiency, nor abnormality: by their tenets, it should be ignored.
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