Could Alz, PD, SPS, MS and Hoffman’s Muscular Dystrophy be, in common with ALS, be related to the Low T3 Syndrome, either as its cause, or its effect?
Incidence of ALS (similar to MS): graphic from Vitamin D Wiki
There are few lethal conditions as poorly understood, as tragic, as unpredictable and as inexorable as ALS (Amyotrophic Lateral Sclerosis, a.k.a. Lou Gehrig’s disease). ALS engenders a sense of helpless inadequacy and frustration in the mind of the observing physician, because its origin is unknown, its timing is unpredictable, its course is relatively rapid and we have no clue as to how to treat it. Twice, I have watched a dear friend waste away, for what seemed to be no good reason!
Here, in brief, are two stories:
CASE 1: An old friend, an anaesthetist with whom I worked for 20 years, married a brilliant young pediatrician, who soon became the chief of pediatrics at a high-end teaching hospital. They had 3 girls, each as savvy as her mother and each, a source of pride and joy, to her parents.
With the youngest aged 12 years, the brilliant pediatrician began to notice a loss of muscle power: soon, beset with ALS, she was just a patient – an MD no more .
After a few short years of careful, constant, loving care by her husband, one of the planet’s most empathetic humans, she lost the battle and became a memory.
CASE 2: Another friend, a diligent, empathetic, and steadfast family physician, faithful father of three and one of my closest friends, developed a high-grade, rapidly progressive cancer of the prostate at age 68. His tumour quickly progressed to bone metastases and was unresponsive to hormone manipulation: shortly after starting chemotherapy, he became progressively weaker and eventually, ALS was diagnosed.
The chemotherapy continued, but he too, lost the battle with ALS, dying prematurely from ALS – not from prostate cancer– in 2019.
The Spectre of ALS
The Spectre of ALS sits, a shadow at the back of my mind, taunting me with every mention of “Neurology”, filling my thoughts with heightening frustration. Had I known then, what I now know, perhaps my hand might have been the one that saved those two exemplary physicians, but I, and all their other medical friends had been unable to help.
I wrote most of this “piece” shortly after the family physician’s demise: I held back on posting it, in case time proved me wrong. But now, here comes that spectre againI and I’m upset, once more – one of my sons came to see me, lamenting the fate of a friend’s wife, who chose “MAID” over the slow death of ALS.
But now I am a SUBSTACK blogger: perhaps – just maybe – by publishing my thoughts, I can interest and motivate some forward-thinking and well-connected researcher, to find the answer to the vexing question of Lou Gehrig’s disease.
With that in mind, I googled “ALS T3 reverse T3”: Google led me to the single, easily available article on the subject, – ”T4, T3 and RT3 Levels In Serum And Cerebrospinal Fluid Of Patients With Amyotrophic Lateral Sclerosis”, published in the journal “Neurology”, in January 1989, authored by J P Malin 1, R Ködding, H Fuhrmann, A von zur Mühlen – PMID: 291-5230, DOI: 10.1007/BF00314221, URL https://pubmed.ncbi.nlm.nih.gov/2915230/
Here is the Abstract:
“Thyronine (T4), Triiodothyronine (T3), and reverse-triiodothyronine (rT3) levels were evaluated in cerebrospinal fluid (CSF) and in serum of 12 patients with definite Amyotrophic Lateral Sclerosis (ALS) by specific radioimmunoassays.
Circulating microsomal and thyroglobulin antibodies were also evaluated: in all patients, serum levels of T4, T3 and rT3 were within normal limits**; but In CSF, the rT3 levels were significantly elevated to 0.118 micrograms/l (mean). The T4 levels were not significantly elevated and the T3 levels were below the detection limit of 0.03 micrograms/l ………… (!).
In other words, the T3 level in the CSF was ZERO, which means that the T3/rT3 ratio was also, zero: these patients had LowT3 in the central nervous system, but doubtless, LT3 S was present throughout their bodies.
** The authors did not specify their “normal limits”, so I can’t comment on the presence or absence of LT3 S. However LT3S develops in all severe and chronic diseases, so I conclude that the levels in the CSF were a reflection of the situation in all the other organs.
According to the authors, “a correlation between the elevated rT3 levels in CSF and the severity or type of ALS could not be demonstrated by this study, especially since the antithyroid antibodies (thyroglobulin and microsomal antibodies) showed normal titres and did not suggest disturbances of thyroid autoimmunity in patients with ALS.” ***
*** Here’s the “kicker”: “thyroid autoimmunity” is not a prerequisite for the development of LT3 S. LT3 S is is diagnosed on the basis of T3/R T3 ratio and since they referred to the serum levels simply as “normal”, no conclusion can be drawn about the severity of LT3 S, in their series of ALS patients.
Chat GPT
This being 2025, the year of AI, I put the question to Chat GPT – and it responded: ”Cerebrospinal Fluid (CSF) Analysis (PubMed): in a smaller study of 12 ALS patients, rT3 levels in CSF were significantly elevated, while T3 levels were below detection limits and T4 levels showed no significant change. However, there was no correlation between elevated rT3 levels and ALS severity or type.” Evidently, chat GPT had only found the article which I had already read, so it seems that there are no similar articles available, within the purview of chat GPT.
Anyway, Chat GPT continued, in a paragraph entitled “clinical implications” (below):
“Clinical Implications:
The elevation of rT3 in CSF, without corresponding changes in serum levels, suggests that alterations in thyroid hormone metabolism may occur locally in the central nervous system in ALS. However the lack of correlation with disease severity and the absence of consistent findings across studies indicate that these changes may not have a direct pathological role in ALS” (Rupa Health). ****
**** rt3 produced in the tissues passes immediately, from the cells to the serum and is cleared from the serum in the kidneys: hence, a blood test shows a low level: rT3 produced in the central nervous system passes into the CSF, and “has nowhere to go”. Patently therefore, CSF levels of rT3 can be expected to be much higher than serum levels.
The authors continued:
”Given the current evidence, routine measurement of rT3 and free T3 in ALS patients is not recommended, and these markers should not be used to guide clinical management. Further research is needed to understand the potential role of thyroid hormone metabolism in ALS and its implications for disease progression and treatment.
If you have concerns about thyroid function in the context of ALS, it’s advisable to consult with a healthcare provider who can interpret thyroid hormone levels in the context of your overall health and clinical presentation.”
MY COMMENT, regarding Chat GPT’s assessment:
This concluding statement, recurrent in papers which discuss atypical thyroid hormone profiles, is the annoying “cop out” – the “stumbling block“, which has prevented doctors from coming to reasonable conclusions regarding thyroid function for the past four decades!
The edicts “Don’t use Free T4 or T3 to screen for hypothyroidism” and “do not test for reverse T3” are neither fair nor reasonable, even although they are part of the ministry of health’s “choosingwiselycanada” platform: “choosing wisely”, as advertised, is “a campaign to help physicians and patients have conversations about unnecessary tests, treatments and procedures”.
However such a statement, coming from the MOH, which has direct control over doctors’ licenses and livelihoods, is interpreted by the “grassroots” physician as a blanket ban on testing T3: what that means is that a citizen suffering from LT3 S hasn’t got a hope of being diagnosed.
The MD should, as he used to be, free to use his/her judgement, in the investigation and management of patients: “one-size-fits-all” should not be applied to the practice of medicine!
In the face of known facts regarding stress-related hypercortisolemia, its effects on T4–T3 conversion and rT3 production in humans, the resulting intracellular T3 starvation and minimization of serum Free T3 (not to mention the effects of T3 deficiency on the brown fat and the myocardium), I am forced to comment: Permitting the voice of authority to instruct us that “Measurement of T3 and rT3 in ALS patients is not recommended” is, to say the least, obfuscatory: at worst, one is tempted to postulate that the reason for the copout is to avoid rocking the Eltroxin boat, by pointing out that the logical treatment for a problem due to Low Thyroid 3, is to prescribe Thyroid 3!
Anyway, I continued to query AI, beginning with “Please tell me about T3, rT3 and the T3/rT3 ratio in neurological diseases, including Alzheimer’s, Parkinson’s, Stiff Person Syndrome, Multiple Sclerosis and ALS: I need a comment on the Low T3 Syndrome in neurological disease.”
Chat GPT “Thought, for 18 Seconds”.
Then it came up with the best explanation of LT3S which have thus far seen, outside of my own articles (viz): it’s answer was as follows:
“INTRODUCTION: Euthyroid sick syndrome—often termed “Low T3 Syndrome”—is characterized by decreased serum Triiodothyronine (T3) levels, elevated serum reverse T3 (rT3), normal or low thyroid‐stimulating hormone (TSH) concentrations and low or subnormal Thyroxine (T4), in patients without intrinsic thyroid disease.
It is classically seen in critical illness, with low F T3 being the most frequent abnormality (≈70% of hospitalized patients) and rT3 elevations resulting from down-regulation of Deiodinase-1 activity, plus up-regulation of Deiodinase-3, which converts T4 to T3 and rT3 to inactive T2 (NCBIMedscape).
Chat GPT continued: “Increasingly, similar alterations have been documented in chronic neurological disorders, suggesting that a systemic or central “tissue hypothyroidism” may contribute to neurodegenerative processes.”
NOTE:
Chat GPT, by not identifying the “neurological disorders”, implied that “tissue hypothyroidism” ( a.k.a. “Intracellular Hypothyroidism”, “intracellular T3 starvation”, “LT3 S”, “euthyroid sick syndrome”, etc.) is related to neurological disease, in general., either as effect (indubitable), or as cause (possible, especially in demyelinating diseases),
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