Optimizing thyroid levels for longer lifespan?

#1

I feel like we don’t discuss thyroid health much on here so I’m hoping to get a discussion going.

In my personal case, I have an optimal TSH (1.6) and Free T4 (1.4), but my Free T3 runs on the low end of the normal range (2.7).

I have a bunch of links saved in my notes so I’m going to share them here.

The impact of thyroid hormone dysfunction on ischemic heart disease. 2019 study

Thyroid Dysfunction in Heart Failure and other Cardiovascular Outcomes
https://www.ahajournals.org/doi/10.1161/CIRCHEARTFAILURE.118.005266?fbclid=IwAR0UUzJVMK5mcownP4vOEKES1urH5Vjqc-bC0krT2hR5UcPcUKBIcePi57A&

Thyroid Replacement Therapy and Heart Failure
http://circ.ahajournals.org/content/122/4/385.extract

Thyroid Hormone and Cardiac Disease: From Basic Concepts to Clinical Application

The Role of Thyroid Hormone Therapy in Acutely Ill Cardiac Patients

T3 Therapy Lowers the Incidence of Atrial Fibrillation After Cardiac Operations
http://www.annalsthoracicsurgery.org/article/0003-4975(96)00102-6/abstract

T3 Effects on Cardiovascular System in Patients with Heart Failure

Relation Between Free T3/Free T4 Ratio, Echocardiographic Parameters and Mortality in Dilated Cardiomyopathy
http://onlinelibrary.wiley.com/doi/10.1016/j.ejheart.2004.04.016/full

Low-T3 Syndrome: A Strong Prognostic Predictor of Death in Patients with Heart Disease
http://circ.ahajournals.org/content/107/5/708.full

Low Thyroid Hormone Increases Risk of Death from Heart Attack by 70%

Low T3 Syndrome: A Strong Predictor of Low Cardiac Output and Death in Patients Undergoing Coronary Artery Bypass Grafting
http://www.annalsthoracicsurgery.org/article/S0003-4975(14)00328-2/fulltext

Acute Effects of T3 Replacement Therapy in Patients with Chronic Heart Failure and Low-T3 Syndrome
http://press.endocrine.org/doi/full/10.1210/jc.2007-2210

Safety and Hemodynamic Effects of Intravenous T3 in Advanced Congestive Heart Failure

Low T3: A Strong Predictor of Outcome in Acute Stroke Patients

  1. Symptomatic Relief is Related to Serum Free Triiodothyronine Concentrations during Follow-up in Levothyroxine-Treated Patients with Differentiated Thyroid Cancer - Larisch, Midgley , Dietrich and Hoermann. See: Thieme E-Journals - Experimental and Clinical Endocrinology & Diabetes / Abstract (This paper clearly proves that FT3 concentrations are the most important in clinical decision making, as they are most closely linked to residual hypothyroid symptoms in T4- Only treated patients. It also shows that in-range TSH is not sufficient for symptom relief.).

  2. Homeostatic equilibrium between free thyroid hormones and pituitary thyrotropin are modulated by various influences including age, body mass index and treatment - Hoermann R1, Midgley JE, Giacobino A, Eckl WA, Wahl HG, Dietrich JW, Larisch R. See: Homeostatic equilibria between free thyroid hormones and pituitary thyrotropin are modulated by various influences including age, body mass index and treatment - PubMed ((This is a great paper, although complex. It shows that it is the relationships of the thyroid hormones, and how they adjust during treatment, that counts. It also makes it crystal clear that TSH should only have a supporting role in the assessment process during treatment.)

  3. Recent Advances in Thyroid Hormone Regulation: Toward a New Paradigm for Optimal Diagnosis and Treatment - Hoermann, Midgley, Larisch, Dietrich. See: Frontiers | Recent Advances in Thyroid Hormone Regulation: Toward a New Paradigm for Optimal Diagnosis and Treatment

  4. Thyroid hormone replacement - a counterblast to guidelines - Dr A.D. Toft. See: http://www.rcpe.ac.uk/sites/default/files/jrcpe_47_4_toft.pdf

  5. Consensus statement for good practice and audit measures in the management of hypothyroidism and hyperthyroidism - M P J Vanderpump, J A 0 Ahlquist, J A Franklyn, R N Clayton, on behalf of a working group of the Research Unit of the Royal College of Physicians of London, the Endocrinology and Diabetes Committee of the Royal College of Physicians of London, and the Society for Endocrinology See: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2351923/pdf/bmj00557-0041.pdf

In patients with a left ventricular ejection fraction of greater than 40% (study II), triiodothyronine (T3) administration resulted in significantly improved stroke volume (p less than 0.01) and cardiac output (p less than 0.02) and reduced systemic (p less than 0.01) and pulmonary (p less than 0.05) vascular resistances. There were no adverse reactions to triiodothyronine in the dosages that were used. Triiodothyronine appears to be beneficial to all patients undergoing open heart surgery.

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#2

Thanks for starting this discussion. I re-started thyroid therapy a few months ago, after having been on it briefly about 5 years ago. It was the link to heart health that led me to more actively manage that issue. I’m having a better outcome with the Armour natural thyroid this time around as compared to the levothyroxine 5 years ago.

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#3

I got t3 of 38 on the latest test, CR decreases T3, recently on semaglutide but not long enough

#4

Ashwaghanda may affect the thyroid. From ConsumerLab.

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#5

When I used to take ashwagandha, I used to see about a 0.2 increase in Free T3 (2.7 to 2.9) which isn’t much, but it was something.

Now I take 100mcg T4 and 12.5mcg T3 and it has improved my T3 level and I feel better. No doctor would have prescribed them to me if they only went by my 1.6 TSH and 1.4 Free T4, but I definitely notice a big difference in my energy level by self medicating this way since my T3 got a bump from the lower end of normal to a more optimal level.

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#6

I’m glad there are people who understand thyroid function here! I am hypothyroid and we tinker with my t3/t4 because I have fatigue/blah issues, and this is one area where I think I could be managed better. My ADD keeps me from reading/focusing on all the numbers long enough to absorb what it all means (the I can’t read a study to save my life thing) .

I’ll post my numbers and see if anyone has anything to say, if you’d be so kind

In March
my free t4 was .9
My tsh was 2.17

We tweaked my rx and kept my t3 at 20 and bumped my t4 slightly to 110 mcg sr c (no idea what the c means!)
T3/t4 20/110 mcg (sr) (c)

I have had more energy and focus since changing, but I also started rapa, so ??

I need to retest soon, but if anyone has suggestions based on those numbers (if they should be higher or lower), I’m all ears

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#7

If you feel better and continue to sustain the better feeling. I don’t see the problem. I used to think the Free T3 level was very important but I find it to be more reliable before we start taking thyroid hormone, and unreliable when we are taking it. I am starting to see some doctors actually place more value in Total T3 as opposed to Free T3, so it might be worth checking next time.

I understand the evidence is mixed here so some of my opinions are anecdotal.

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#8

Lower T3 IS BETTER for longevity

https://www.sciencedirect.com/science/article/abs/pii/S0047637416301804

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#9

This contradicts a few of the studies I shared in the original post, so it’s a bit strange.

Low T3 levels lead to a very poor quality of life.

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#10

On the clinical side of things as to what I do … TSH upper limit of normal is 2.5 … not what the labs report up to 4.5-5.5.
Free T3 is the active hormone, and the conversion of T4 to T3 is zinc/selenium mediated.

It’s an interesting area, but if dysfunctional, AND Cortisol/Melatonin/Sex Hormones are normalized - then certainly address this, but make sure especially cortisol curve is normal before thinking Thyroid is the primary issue (unless having +Thyroid autoantibodies and low Free T3).

I think an important point for so many people is get to a point where you feel well … measure EVERYTHING hormonal; and when things seem to go badly, remeasure and see what has moved, and work on getting it back to when you were feeling great. Also, be aware, you could have something else going on, but hormones are incredibly important and it is a balance between all of them.

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#11

@ConquerAging
Mike Lustgarden just put out a new video on this

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#12

More than a decade ago, I recall reading a reference to a retrospective observational study associating slightly low metabolism/free T3 levels being associated with longevity. Does anyone recall a specific study to that effect?

#13

I remember but I’m very skeptical. It reminds me of the study where castrated rats with low testosterone lived longer. Low T3 levels are undoubtedly linked to cardiovascular disease and healthspan would be atrocious with low thyroid levels.

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#14

Cautionary Tale
I finally got around to listening to an old Attia member-level podcast on thyroid hormones. I had thought I was mostly on top of those issues but the podcast made me realize I might be missing a point or two.

This morning I dug out last year’s comprehensive panel (I’m, due for this year’s test), calculated my Free T3/Reverse T3 ratio, and plugged my findings into GPT-4o and two other LLMs. Even though all of my primary readings were in the normal range, GPT offered the following interpretations. For context, my body temps run 1-2 degrees F below the old school 98.6. I have very low inflammation, healthy body weight and composition, and am not cold or tired, nor do I chill easily. Still . . .

Prompt
In order of likelihood, what are the two most likely diagnoses and treatments given following thyroid measurements: TSH=low normal range, Free T4=mid-normal range, Free T3=low normal range, Reverse T3=high normal range, Free T3/Reverse T3 Ratio=Borderline low range. Conduct a deep analysis.

ChatGPT

Based on the thyroid function test results you provided:

  1. TSH (Thyroid Stimulating Hormone): Low normal range
  2. Free T4 (Thyroxine): Mid-normal range
  3. Free T3 (Triiodothyronine): Low normal range
  4. Reverse T3: High normal range
  5. Free T3/Reverse T3 Ratio: Borderline low

Here are the two most likely diagnoses:

1. Non-Thyroidal Illness Syndrome (NTIS) (also known as Euthyroid Sick Syndrome)

Diagnosis Rationale:

  • Low normal Free T3 combined with a high reverse T3 is characteristic of NTIS. This condition is often observed in patients with acute or chronic illness (e.g., sepsis, trauma, or chronic inflammation), where the body downregulates thyroid hormone activity to conserve energy.
  • TSH in the low-normal range and Free T4 in the mid-normal range support the notion that this is a peripheral thyroid metabolism problem rather than an issue with the thyroid gland itself.
  • In NTIS, the body preferentially converts T4 into reverse T3 (an inactive form) rather than into the active T3, leading to a high reverse T3 and a low T3/reverse T3 ratio.

Likely Treatment:

  • Observation: NTIS is often a transient phenomenon associated with systemic illness, and treatment generally focuses on addressing the underlying illness. In most cases, thyroid hormone supplementation is not recommended unless there is clear evidence of hypothyroidism.
  • Management of underlying illness: If an acute or chronic illness is present, treatment should focus on resolving or stabilizing the primary condition, after which thyroid function often normalizes on its own.

2. Subclinical Hypothyroidism with Impaired T3 Conversion

Diagnosis Rationale:

  • The low-normal TSH and mid-normal Free T4 suggest that the thyroid gland is producing sufficient levels of T4. However, the low normal Free T3 combined with high reverse T3 may indicate that peripheral conversion of T4 to T3 is impaired, leading to a relative deficiency in the active hormone (T3) despite adequate T4 levels.
  • This could occur due to chronic stress, chronic illness, nutrient deficiencies (e.g., selenium, zinc), or impaired liver function, all of which can alter deiodinase enzyme activity, resulting in increased reverse T3 production.
  • The Free T3/Reverse T3 ratio being borderline low suggests that the patient may not be converting T4 into active T3 effectively, even though the gland itself is functioning relatively normally (e.g., not a primary hypothyroid condition).

Likely Treatment:

  • T3 supplementation: In some cases, particularly if the patient is symptomatic (e.g., fatigue, cold intolerance, weight gain), treatment with a small dose of liothyronine (T3) may be considered. This would help improve T3 levels and address symptoms related to impaired T3 conversion.
  • Addressing potential underlying factors: If factors such as nutrient deficiencies, stress, or liver dysfunction are suspected, addressing these issues could improve the conversion of T4 to T3. Selenium supplementation, for example, may improve deiodinase activity, which is responsible for converting T4 into T3.

Deeper Analysis:

  • The results suggest a peripheral thyroid hormone metabolism issue rather than a primary thyroid dysfunction (e.g., hypothyroidism or hyperthyroidism). Both NTIS and impaired T4 to T3 conversion are non-primary thyroid disorders.
  • Reverse T3 is often elevated in conditions where stress, inflammation, or chronic illness is present, suggesting that systemic factors could be at play in regulating thyroid hormone activity.
  • T3 is the more biologically active form of thyroid hormone, and low T3 relative to reverse T3 can lead to symptoms of hypothyroidism, even in the presence of normal TSH and Free T4 levels.
  • These conditions can coexist with non-thyroidal influences (such as nutrient deficiencies or chronic illness), so a multifactorial approach is often necessary to achieve optimal treatment outcomes.

Conclusion:

  • The most likely diagnosis is Non-Thyroidal Illness Syndrome (NTIS), particularly if the patient has an underlying illness or stress. The second possibility is Subclinical Hypothyroidism with Impaired T3 Conversion, especially if there are symptoms of hypothyroidism and systemic issues affecting deiodinase function.
  • Treatments typically revolve around managing the underlying cause of thyroid dysfunction or addressing peripheral hormone conversion deficiencies through T3 supplementation or nutritional support.
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#15

I’m amazed that chat GPT was able to do all of this. I didn’t know I could plug in lab results and get this much info.

It sounds like we have exactly the same issue. Reduced conversion of T4 to T3, without any issue with the thyroid gland itself. I’ve had this issue for a number of years, despite having no nutrient deficiencies that would impair conversion. I’m taking 180mg NP Thyroid for it. I had severely symptomatic previously. My Free T3 went as low as 2.4, but I had symptoms on 2.9. My TSH and Free T4 have always been great.

#16

I have worked some with all of the public LLMs. On balance, I believe GPT-4o leads in this particular area (and many more), followed by Claude’s advanced versions. With all LLMs, what you get out depends greatly on crafting the prompt. Omit or change a few words in the wrong direction and you will get much less or even different answers. With Chat, I have written a permanent meta-prompt to treat all relevant queries as a conversation between one research scientist and another. Among other things, this omits the medical warnings, etc. in most cases and engages a higher level of analysis.

On your analysis. Do you have Reverse T3 reading? In many cases, this value and the Free T3/Reverse T3 ratio (you have to convert the readings first) is required to discriminate among possible causes and issues. Without them, you may experience improvement with NP but it will be masking (maybe overpowering is a better term) the underlying causality, which may or may not have consequences.

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#17

Just for fun, I typed the same prompt into Dr. Oracle which had a higher score than Chat GPT on the medical licensing exam.

I don’t have the medical expertise to judge the relative merits of the responses.

Most Likely Diagnoses and Treatments for Given Thyroid Measurements

  1. Euthyroid Sick Syndrome (ESS)

Diagnosis

Most likely diagnosis based on the provided thyroid function test results

Characterized by low T3 levels with normal TSH and T4 levels ([1])

Often seen in patients with non-thyroidal illness or malnutrition

Clinical Considerations

Typically a transient condition that resolves with recovery from underlying illness

Not a primary thyroid disorder, but rather an adaptive response to stress or illness

Treatment

Generally, no specific treatment for thyroid function is required

Focus on addressing the underlying condition causing ESS

Thyroid hormone replacement is not recommended unless there is clear evidence of primary hypothyroidism ([2])

2. Subclinical Hypothyroidism

Diagnosis

Second most likely diagnosis, although less probable given the normal TSH

Typically characterized by mildly elevated TSH with normal free T4 levels

In this case, the low-normal TSH and low-normal free T3 could suggest early stages

Clinical Considerations

May progress to overt hypothyroidism in some cases

Associated with increased cardiovascular risk and subtle symptoms of hypothyroidism

Treatment

Treatment decisions should be individualized based on clinical presentation and risk factors

For TSH levels < 10 mIU/L, treatment is generally not recommended unless there are specific risk factors or symptoms ([3])

If treatment is initiated:

Levothyroxine is the standard treatment

Starting dose typically 25-50 mcg daily, adjusted based on TSH levels

Goal is to achieve TSH within the reference range

Differential Considerations

Central Hypothyroidism

Less likely but should be considered if clinical suspicion is high

Characterized by low or normal TSH with low or low-normal thyroid hormone levels

Further evaluation of pituitary function may be warranted if suspected

Non-Thyroidal Illness Syndrome (NTIS)

Similar to ESS, but typically seen in more severe illnesses

Can present with various patterns of thyroid function abnormalities

Caveats and Additional Considerations

Interpretation of thyroid function tests should always be done in the context of the patient’s clinical presentation ([4])

Repeat testing may be necessary to confirm the diagnosis, especially if results are borderline

Consider potential interfering factors such as medications, pregnancy, or recent iodine exposure ([5])

The high-normal reverse T3 and borderline low free T3/reverse T3 ratio may suggest impaired T4 to T3 conversion, which can be seen in various conditions including ESS

Always rule out laboratory errors or assay interferences before making a definitive diagnosis ([1])

:speech_balloon: Ask a follow-up question here. Topic will be limited to the above discussion.

References

Pitfalls in the measurement and interpretation of thyroid function tests. (Best practice & research. Clinical endocrinology & metabolism, 2013)

Biochemical Testing of the Thyroid: TSH is the Best and, Oftentimes, Only Test Needed - A Review for Primary Care. (Clinical medicine & research, 2016)

2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis. (Thyroid : official journal of the American Thyroid Association, 2016)

Thyroid function tests. Guidelines for interpretation in common clinical disorders. (Postgraduate medicine, 1989)

2017 Guidelines of the American Thyroid Association for the Diagnosis and Management of Thyroid Disease During Pregnancy and the Postpartum. (Thyroid : official journal of the American Thyroid Association, 2017)

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#18

And still another AI, Mayo Clinics platform.

They are all in agreement that ESS is the most likely diagnosis.

For things not life-threatening, maybe we can just ask AI without a trip to the doctor.

It seems more plausible than an online visit with a doctor.

“Given the thyroid measurements provided—low normal thyroid-stimulating hormone (TSH), mid-normal free thyroxine (FT4), low normal free triiodothyronine (FT3), high normal reverse triiodothyronine (rT3), and a borderline low FT3/rT3 ratio—the two most likely diagnoses are euthyroid sick syndrome (ESS) and central hypothyroidism.”

1. Euthyroid Sick Syndrome (ESS):

• ESS, also known as non-thyroidal illness syndrome, is characterized by alterations in thyroid function tests in the setting of non-thyroidal illness without intrinsic thyroid disease. The typical pattern includes low or low-normal FT3, normal or low-normal FT4, and elevated rT3, which aligns with the provided measurements. The FT3/rT3 ratio is often low in ESS due to impaired peripheral conversion of T4 to T3 and increased conversion to rT3.[1]

• Treatment: Generally, no specific thyroid hormone treatment is required for ESS. Management focuses on treating the underlying illness. Thyroid function typically normalizes once the primary illness resolves.[2]

2. Central Hypothyroidism:

• Central hypothyroidism is due to insufficient stimulation of the thyroid gland by TSH, often secondary to hypothalamic or pituitary dysfunction. This condition can present with low or low-normal TSH, normal or low-normal FT4, and low FT3. The high rT3 and borderline low FT3/rT3 ratio can also be seen in central hypothyroidism due to impaired T4 to T3 conversion.[1][3]

• Treatment: The primary treatment is thyroid hormone replacement, typically with levothyroxine (LT4). The dosage should be titrated to maintain FT4 in the upper half of the reference range, as TSH is not a reliable marker in central hypothyroidism.[3]

In summary, the most likely diagnoses are euthyroid sick syndrome and central hypothyroidism, with treatments focusing on managing the underlying illness for ESS and thyroid hormone replacement for central hypothyroidism.

#19

Always amusing and 4o seems to be holding up well cf. the medically specialized LLMs. OpenAI offers many private highly specialized versions of GPT; one or more in the above chart are likely to be offspring of GPT parents.

Two interesting question are the R^2 between medical licensing exams and diagnostic skills in humans, and the same question applied to LLMs. In the law and the behavioral sciences, these correlations are surprisingly low.

Based on many hundred queries, not all medical but all scientific, the shortfall I see in the best of the current models is a tad too much “desire” to please the human, making them susceptible to poorly written “leading question” prompts. Be careful of that. Still, with good prompts and probing as necessary, I find the the LLMs provide valuable evidence and, again with the right prompts, to display few fabrications.

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#20

“I see in the best of the current models is a tad too much “desire” to please the human”
Perhaps I see that a little with Chat GPT and Bard, but I do not think that is generally the case,

When I am at the doctor’s office, I often feel I am not able to frame my symptoms properly because I feel time constrained and the doctor’s follow-up questions indicate that I am not accurately describing my symptoms.

I am much more comfortable taking my time to produce a proper AI prompt for Dr.Oracle and
Mayo’s OpenEvidence.

The AI, responses seem to be more accurate. I don’t think that they are trying to please me
The fact that I can get the same diagnosis from more than one AI is reassuring, like getting a second doctor’s opinion that agrees with the first doctor’s opinion.

I see the day, if it is not already happening, when your doctor consults AI first before giving a diagnosis. I would feel better if my doctor did this. Doctors could be trained in the art of the AI prompt.

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