Some ideas you could consider -
-high dose t4 only (300mcg/day).
-TRH ( Thyrotropin-releasing hormone) which seems to be more hypothalamus than pituitary.
-You ever tried a dopamine reuptake inhibitor like ritalin, wellbutrin, vyvanse? I recall you tried the modafinil, but these products are a little bit different.
While both overt hyperthyroidism (suppressed TSH, high free T4/T3) and overt hypothyroidism (very high TSH, low free T4) are associated with significantly increased morbidity and mortality in all age groups, those of us nearing 70 or older may want to evaluate their thyroid status differently by considering that borderline low T4 with borderline high TSH may be associated with longevity. The Leiden Longevity Study identified a thyroid phenotype characterized by higher-than-average TSH levels in conjunction with free T4 levels in the low-normal range. This suggests a centrally-mediated reset of the hypothalamic-pituitary-thyroid axis. This state may be a heritable trait associated with a slower metabolic rate and, ultimately, a longer, healthier lifespan but it might also be modifiable, conferring similar benefits.
There are a number of studies and findings on this topic (not mentioned here) that older adults may find interesting. The generalization is that a low normal or even mildly subclinical hypothyroid state is not detrimental in those over 75-80 and, in fact, appears to be a biomarker for, or contributor to, exceptional longevity. Conversely, a high normal or subclinical hyperthyroid state is consistently associated with increased mortality and cardiovascular risk in this population. IMO, the utility of standard TSH reference ranges derived from younger populations is greatly diminished when applied to older adults. Treatment for mild hypothyroidism at these ages may interfere with a potentially adaptive, pro-longevity metabolic state.
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T4 only wasn’t good for me either. My reverse T3 is already high but my hope was to take enough that it would still convert to just enough T3 but my lab level was lower than at baseline.
I actually did try injecting TRH years ago when my symptoms were really bad but I didn’t notice any difference at all.
My symptoms are much much better these days anyway. I just wonder if I’m leaving some energy on the table by having a Free T3 just below 3.
No I’ve never tried the amphetamines
Did you copy this from a link or did you type all this yourself? If there’s a link, I’d be interested in checking it out
These are my thoughts @LukeMV based on a synthesis of reading over the years. You will find many sources related to this discussion. Here are a couple of links I have handy. With a little searching, you will find others even more on point.
More broadly, thyroid function is not the only functional component in which one can find counterintuitive evidentiary trends. SHBG levels in the elderly is another that comes to mind.
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Ah ok. That’s cool you tried injecting TRH! Good to hear your symptoms are much better.
That’s a tough call about the free t3 levels and energy.
If you have never tried ADHD medication (or other reuptake inhibitors) it’s something to try one day.
As there are 3 popular reuptake classes (dopamine, noradrenaline, serotonin) so some people stack various products. Some products have 2 in 1 etc.
Usually serotonin paird with dopamine or noradrenline. Some people do all 3.
I don’t believe Wellbutrin is an amphetamine. A lot of online pharmacies carry it.
Some people on this forum use it with good reviews. It appears to be a bit similar modafinil but more of a energy/motivation feel. Kinda like a more narrow focus (intense concentration).
Don’t know if you’ve read about Nandrolone use and it’s effect on neurotransmitters, but there are some interesting articles on animals/rodents. I’ve seen articles saying it can increase or decrease certain chemicals. Not sure what to think on it however.
https://www.sciencedirect.com/science/article/abs/pii/S0039128X13002195
Just linking a post on the subject from 2023
From chat GPT
Looking much deeper than this basic prompt, you will see an interesting set of relationships for older adults.
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FWIW …
Attia’s podcast on thyroid.{11/17/2025]
Now all trip over themselves,.
My comment;
Wilson was correct over 30 years ago.
“If you wait until you are ready, it is almost certainly too late.”
~Seth Godin
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Great interview. The news of a Free T3 LC/MS test existing and being more reliable than the standard one is huge information to me. I wish he discussed what the results of this test could mean.
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I thought you’d enjoy that episode. And no doc has ever told me about that test, either. Fyi, I see on Good Labs it’s available from Quest for $27
I also didn’t know it led to worse lipids etc, even if your levels are corrected.
I find the entire topic confusing and will listen to the episode again. Did I miss them talking about the ideal levels?
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Oh yes there’s definitely a correlation between low thyroid levels and higher LDL.
Unfortunately, they didn’t discuss optimal results except for TSH really.
I’m going to try and get a Free T3 LC/MS as well
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Journal Article
Published 01, Dec 2016(yes almost a decade)
DIAGNOSIS OF ENDOCRINE DISEASE: “How reliable are free thyroid and total T3 hormone assays”
This is behind a pay wall
https://academic.oup.com/ejendo/article-abstract/175/6/R255/6654920
A summary of this Podcast by Peter Attia, etc.
ChatGPT5.1 Summary:
1. Executive Summary (High-Level Takeaways)
Thyroid physiology is far more intricate than routine clinical screening implies. While most clinicians treat thyroid disease as a “TSH and free T4” problem, the reality is that T3 drives biological activity, and intracellular conversion via deiodinases (D1, D2, D3) determines whether individual tissues experience adequate thyroid signaling. A patient can appear “normal” on labs while specific organs are functionally hypothyroid or hyperthyroid.
In hypothyroidism, Hashimoto’s autoimmune thyroiditis dominates, but a variety of less common etiologies exist. Diagnosis is usually made via elevated TSH with low free T4, but there are subtler cases where pituitary dysfunction, assay interference, medication effects, or chronic illness distort interpretation. Symptoms are notoriously nonspecific: fatigue, weight gain, cold intolerance, dry skin, constipation, hair changes, and cognitive slowing.
Treatment revolves around levothyroxine (T4), but dosing, absorption, adherence, drug interactions, and genetic factors (e.g., DIO2 polymorphisms) create wide inter-individual variability. Some patients report persistent symptoms despite normalized labs; the debate over combination therapy (T4+T3) remains unresolved, with limited evidence supporting broad use but possible benefit in select subgroups. Conversely, overtreatment is common and dangerous: excess thyroid hormone increases risk of atrial fibrillation, bone loss, and arrhythmia.
The interview emphasizes that clinicians should think beyond template protocols — recognizing atypical presentations, carefully evaluating persistent symptoms, and individualizing therapy while avoiding dogma on either side of the T3 debate.
2. Bullet Summary (Key Points)
- T3 is the active hormone; tissue-level thyroid status depends on local deiodinase activity, not just serum labs.
- TSH + free T4 is an oversimplification; labs often fail to reflect organ-specific thyroid signaling.
- Hashimoto’s is the most common cause of hypothyroidism in developed countries.
- Symptoms are nonspecific and overlapping with depression, anemia, menopause, and chronic fatigue.
- Subclinical hypothyroidism requires judgment; treatment isn’t automatically indicated.
- Central (pituitary) hypothyroidism breaks the normal TSH–T4 pattern and is often missed.
- Levothyroxine absorption varies with food, supplements, gut issues, and medications.
- Many patients feel unwell despite “normal” labs — but evidence for adding T3 is mixed.
- A minority with DIO2 polymorphisms may respond better to combination therapy.
- Overtreatment is common and raises fracture and atrial fibrillation risk.
- Thyroid nodules are common and usually benign; ultrasound stratification guides biopsy.
- Silent thyroiditis causes transient hyper → hypo → recovery patterns.
- Hyperthyroidism (Graves’, toxic nodules) is less common but clinically dramatic.
- Graves’ disease involves TSH-receptor–stimulating autoantibodies.
- Treatment options include antithyroid medications, radioactive iodine, or surgery.
- Thyroid eye disease can occur independently of thyroid hormone levels.
- Aging shifts TSH upward; mild elevations may be physiologic rather than pathologic.
- Lab interpretation must consider pregnancy, illness, meds, and assay artifacts.
- “Normal range” is not universal — population and lab variations matter.
- Clinical judgment is essential; algorithms alone miss atypical cases.
Full text of response:
And testosterone! A decent % of guys with slight hypogonadism (ie total T in the 300-400 range) would benefit from addressing thyroid issues, which in turn fixes testosterone. Another well-known gym bro fact which turned out to be true!
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Reving an older thread, but was looking for feedback. I am pretty sure I am trying to over optimize something that isn’t broken, but my TSH has always been high 4-5+. Recently - now in caloric maintenance it’s a bit lower, but not in “optimal range”.
I am have read somewhere that lower thyroid function (higher TSH, lower FT3/FT4) is associated with longevity in centenarian/offspring studies — which makes me wonder if my mildly-down-regulated-but-adequate pattern is actually favorable and best left alone, rather than something to “optimize”.
Thyroid labs (biotin-washed draw):
• TSH: 3.4
• Free T4: 1.6 (range 0.8–1.8) — upper-normal
• Free T3: 3.5 (range 2.3–4.2) — upper-mid normal
• Reverse T3: 19 (upper-normal)
• TPO antibodies: 1 (negative)
• Thyroglobulin antibodies: <2 (negative)
I’ll not the 3.4 is the lowest it’s been that I have recorded - at least in a decade. I have lost some weight and ~11bf in full maintenance mode for several months.
What I make of it so far:
My read is that this looks like a mildly elevated TSH, but with genuinely adequate free hormones (FT4 upper-normal, FT3 upper-mid) and no autoimmunity. So I appear euthyroid at the tissue level; my pituitary just seems to run TSH a bit high. I’m specifically not in the low-FT3 / poor-conversion situation — my FT3 is solid.
The one thing I’m spinning on is the upper-normal rT3 (19) alongside good FT3. My working theory is that it reflects (a) abundant FT4 substrate feeding both conversion pathways, and (b) some physiologic/training stress nudging conversion toward the rT3 off-ramp — i.e., a cortisol/recovery signal rather than a thyroid problem. I exercise frequently and have a higher stress dayjob that doesn’t have great boundaries.
My questions:
- Given good FT3 + negative antibodies, does anyone see a genuine case for intervention here, or does this read as “euthyroid, leave it alone” to you too?
- For those into the longevity angle — do you view a mildly-high-TSH/adequate-FT3 pattern as favorable (the centenarian phenotype) or as something to correct?
- On the upper-normal rT3 with good FT3 — agree this points more at cortisol/physiologic stress than thyroid, or am I missing something?
I queried Claude Opus 4.8 on this to see what the optimal levels are for lowest all cause mortality, and this is what it came back with:
Here’s the evidence-based synthesis. The crucial framing up front: for most of these markers the “lowest-mortality” level is where healthy long-lived people sit naturally, not a number you should drug a healthy person toward. Much of the “low FT3 / high rT3 = death” signal is reverse causation — sick people generate those patterns — and the levothyroxine RCTs (TRUST, IEMO) in subclinical hypothyroidism failed to improve hard outcomes. So read these as a physiological signature of slow aging, not a treatment target list.
Optimal-longevity targets
| Marker | Longevity-optimal zone | Direction of the mortality signal |
|---|---|---|
| TSH | ~1.0–2.5 mIU/L (high-normal tolerated, esp. with age) | U-shaped: both suppressed and ≥10 raise mortality |
| Free T4 | Lower third of range (~0.8–1.1 ng/dL / ~13–15 pmol/L) | Linear — higher FT4 is consistently worse |
| Free T3 | Mid-normal (~2.8–3.4 pg/mL / ~4.3–5.2 pmol/L) | Low FT3 tracks mortality, but mostly as illness marker |
| Reverse T3 | Low-normal | Higher = worse, but it’s a sickness flag, not a lever |
| FT3/FT4 ratio(derived) | Higher | Efficient peripheral conversion = lower mortality |
| TPO antibodies | Negative / undetectable | Positivity → inflammation, AITD progression, stroke |
| Tg antibodies | Negative / undetectable | Same; weaker independent signal |
The reasoning per marker
TSH — aim mid-to-high-normal, not low. The single most striking longevity finding: families bred for exceptional survival run higher TSH. Leiden Longevity Study offspring averaged ~0.8 mIU/L higher TSH around the clock than spousal controls, and lower family mortality among nonagenarian siblings’ parents was associated with higher serum TSH and lower free T4. This replicates in Ashkenazi centenarians. The mechanism is a lower thyroidal response to TSH — the gland is set to idle. Meanwhile the danger is at the edges: subclinical hyperthyroidism (suppressed TSH) and TSH ≥10 both raise total/CVD mortality, heart failure, and AF in the large IPD meta-analyses. In a 6,054-person prospective cohort, higher TSH was not associated with all-cause mortality overall, but cardiovascular-mortality estimates diverged — increased risk in those under 72 and decreased risk in the elderly, which is why the high-normal tolerance widens with age. PubMednih
Free T4 — the cleanest, most actionable target: keep it low. This is the most reproducible signal in the whole field. Higher FT4, even within the normal range, predicts more death. The same cohort found higher free thyroxine associated with all-cause mortality (HR 1.18 per unit) and with cardiovascular mortality in the elderly (HR 1.61). It holds in elderly men (MrOS-Sweden), the Rotterdam Study, and frailty/cognition endpoints. Low-normal FT4 is the cell-level correlate of low metabolic “burn rate.” If any single number matters for your stack, it’s this one. nih
Free T3 — wants nuance, not maximization. Two opposing truths. In hospitalized/elderly populations, low FT3 robustly predicts mortality — but that’s largely non-thyroidal illness syndrome (NTIS), where inflammation downregulates D1/D2 deiodinase. Low-T3 syndrome carried 15.1% vs 4.1% 30-day mortality in non-critically-ill internal-medicine patients, which is prognosis, not a deficiency to correct. Yet in healthy people the picture inverts toward efficiency: the NHANES sensitivity analysis found the highest FT3/FT4 ratio quartile had lower all-cause mortality than the lowest (HR 0.70). Leiden offspring had slightly lower absolute FT3 but a higher FT3/FT4 ratio — they convert efficiently from a low T4 base. So the target is mid-normal FT3 achieved through good conversion, not a high FT3 propped up by high FT4. PubMed CentralPubMed Central
Reverse T3 — a sickness barometer, not a target organ. A 2021 review reports serum rT3 positively correlates with all-cause mortality (HR 1.23), likely due entirely to the adverse effects of non-thyroidal illness, of which rT3 is a sensitive marker. Translation: elevated rT3 tells you the body is shunting T4 down the inactivating D3 pathway because of illness, stress, calorie restriction, or drugs (amiodarone, glucocorticoids). Worth noting for your context — rT3 can rise with carbohydrate restriction, short-term calorie deprivation, poor glucose control, and high-dose soy isoflavone, so aggressive fasting/keto can transiently push it up without pathology. Keep it low-normal; don’t chase it pharmacologically. Sage JournalsOptimalDX
TPO & Tg antibodies — you want them gone. Negative is the target. Beyond predicting progression to overt hypothyroidism and Hashimoto’s, even sub-positive detectable TPOAb has been proposed as a sign of low-grade inflammation with negative health effects in euthyroid people, with associations to arterial wall thickening and stroke. One genuine wrinkle: TgAb behaves oddly metabolically — a large Chinese national survey linked TgAb presence to lower glucose/lipid disorder risk, and the NHANES autoimmunity cohort found TgAb inversely associated with hypertension — so its independent mortality contribution is muddier than TPOAb’s. Net: undetectable is ideal; isolated low-titer TgAb in a euthyroid person with normal FT4 is a softer flag than positive TPOAb. Oxford Academic
The integrated longevity phenotype
The slow-aging thyroid signature is internally coherent: high-normal TSH + low-normal FT4 + adequate FT3 via a high FT3/FT4 ratio + low rT3 + no antibodies. It’s a gland set to low output with efficient peripheral conversion — the endocrine equivalent of the mTOR/IGF-1 downregulation you already track. The two findings with the strongest causal plausibility (versus reverse-causation confounding) are low FT4 and high TSH; the FT3/rT3/antibody panel is more diagnostic-of-context than target-able.
One caveat for the report you’re likely building from this: nearly all of it is observational, and no trial has shown that nudging a euthyroid person’s FT4 to the low-normal end extends lifespan. The honest claim is association with a longevity phenotype, not demonstrated benefit from intervention.
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And commentary on your specific results:
Rating against the longevity-optimal zones
| Marker | Value | Optimal zone | Grade | Read |
|---|---|---|---|---|
| TSH | 3.4 | ~1.0–2.5 | C+ | High-normal — but the “wrong kind” of high (see below) |
| Free T4 | 1.6 | lower third (~0.8–1.1) | D | Upper range — the main detractor |
| Free T3 | 3.5 | mid-normal (~2.8–3.4) | A– | Adequate, slightly above mid — no NTIS, good |
| Reverse T3 | 19 | low-normal | C+ | Mildly high, consistent with the high T4 substrate |
| FT3/FT4 ratio | ~0.26 | higher | C | Middling conversion — not the efficient-converter phenotype |
| TPO Ab | 1 (neg) | undetectable | A+ | Ideal |
| Tg Ab | <2 (neg) | undetectable | A+ | Ideal |
The integrated read
The autoimmune panel is flawless — negative TPO and Tg with no detectable titer is exactly the longevity-optimal state. Nothing to improve there.
Free T4 is the problem, and it’s the marker that matters most. Recall that high FT4 — even inside the reference range — is the single most reproducible adverse longevity signal in the literature (HR ~1.18 per unit, plus frailty and CVD-mortality associations). At 1.6 ng/dL this person sits in roughly the top fifth of the range, which is the opposite of the slow-aging signature. The whole longevity phenotype is a gland set to idle: low FT4 with adequate downstream T3. This gland is running warm.
The TSH–FT4 coupling is discordant, and that’s the most interesting finding. Normal feedback says a high FT4 should suppress TSH. Here you have high-normal TSH (3.4) sitting alongside high FT4 (1.6) — they’re moving the same direction instead of opposite. So don’t be misled into reading the 3.4 as “longevity-like”: the Leiden/Ashkenazi high-TSH signal is protective only because it’s paired with a low-output gland (low FT4). High TSH + high FT4 is not that phenotype; it’s an uncoupled pattern. Benign explanations dominate — diurnal timing (TSH peaks late night/early morning, so an early draw inflates it), normal assay variability, or non-simultaneous interpretation. A less common one worth keeping on the radar only if it persists across repeat draws is a mild central set-point quirk (the resistance-to-thyroid-hormone family of patterns presents as FT4 high-ish with non-suppressed TSH). One clean morning fasting recheck would tell you whether the discordance is real or a timing artifact.
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Thank you btw. I am going to do a clean test in a few weeks. That being said, unless something changes, I am not exactly sure I am fixing anything that is really broke (outside of a high t4). More t3 in think may cause more issue and I am not uber symptatic today.
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