FT4 levels on tests and brain fog

[trtthings]

I'm wondering if my brain fog has to do with thyroid hormones.

It seems to get a lot worse on days I don't take anastrozole. Testosterone promotes conversion of T4 to T3, and estradiol does the opposite. Inflammation also suppresses this conversion.

So my thyroid levels over time have been:

3rd of march:
TSH mU/l: 2.8 (reference: 0.4 - 4, seems.. fine..)
FT4 pmol/l: 13.2 (reference range 10.3 - 24.5) - definitely seems to be on the lower end, given age..

2nd of June:
TSH: 1.27 (reference range 0.30 to 4.20 at this lab) - seems.. alright..
FT4: 17.2 (lab range 12 - 22 at this lab). Seems okay here.

10th of August:
TSH: 2.7
FT4: 13.8 (seems low again)
FT3: 4 (range 2.8 - 6.5) - can't complain here.

 

[Vince]

I should also check your reverse T3. You could be pooling your T3. Have you ever had antibodies checked?

 

[trtthings]

I should also check your reverse T3. You could be pooling your T3. Have you ever had antibodies checked?

No I don't think I've had that. I also wonder if they measure reverse T3 at all in my country. If reverse T3 is high, would you benefit from T3 supplementation? I have had a few autoimmune markers measured as elevated but nothing definite.

What fits for me is fatigue, feeling horrible, dry skin, digestion is slow and cold intolerance. And the brain fog which seems to be a common complaint.

Testosterone seems to do a great deal of combating the fatigue.

 

[MarcoFL]

I agree with Vince. you need to know what your RT3 is. I have a tough time converting so on a larger dose of T3 with 1 grain of NDT. T4 only makes me very sick!

 

[trtthings]

I agree with Vince. you need to know what your RT3 is. I have a tough time converting so on a larger dose of T3 with 1 grain of NDT. T4 only makes me very sick!

How did you guys decide to get tested and what is it mainly that the thyroid meds are doing for you? Heat tolerance, mood, less brain fog?

 

[JoeMatts]

Anecdotally, my hypothyroid symptoms - low body temps and pulse, fatigue, dry skin, digestive issues, etc - have always correlated with my fT4 and total T4, even when fT3 was top of the range, and TSH was within range, but slightly elevated. These symptoms started following an extended period of severe caloric restriction, prolonged fasting and excessive exercise — all of which are suppressive to thyroid function on various levels.

TSH directly stimulates D2 deiodinase which controls T4 -> T3 conversion. As overall output from the thyroid begins to decline, the pituitary can compensate by increasing TSH production to not only direct increased thyroid hormone output, but also to maintain circulating T3 by increasing D2 activity, and thus peripheral T4 -> T3 conversion. This situation may manifest as moderate-high fT3, but a barely in-range fT4 and total T4, with a slightly elevated TSH between 2.5 - 4. However, although circulating T3 levels are maintained, there are various cells which rely solely on the uptake of T4 for local conversion to T3 rather than the direct uptake of T3 itself, which is why maintaining an optimal total and fT4 is extremely important, despite T4 itself being a largely inactive hormone — this is especially true for cells in the CNS, as T4 crosses the blood-brain-barrier more readily than T3; google 'hyperthyroid dementia' which can result from high-dose T3 monotherapy suppressing systemic T4 levels for more information.

My own thyroid panel has always fit the above, and my body temps, heart rate and other hypothyroid symptoms respond strongly to taking thyroid hormone, despite all my labs being within range, and fT3 being 'optimal'. Unfortunately, I struggle to tolerate thyroid hormone long-term as it causes my cortisol to drop below range which produces extremely severe symptoms, and subsequently the forced cessation of treatment. Low cortisol is often associated with hypothryoidism as the adrenals themselves require adequate thyroid hormone for cholesterol -> pregnenolone conversion, and thus the production of their own hormones.

I'm hoping some combination of thyroid + hydrocortisone and/or pregnenolone and/or progesterone will allow me to make progress in addressing my hypothyroid symptoms, but there is still a lot of experimentation needed.

 

[Vince]

Anecdotally, my hypothyroid symptoms - low body temps and pulse, fatigue, dry skin, digestive issues, etc - have always correlated with my fT4 and total T4, even when fT3 was top of the range, and TSH was within range, but slightly elevated. These symptoms started following an extended period of severe caloric restriction, prolonged fasting and excessive exercise — all of which are suppressive to thyroid function on various levels.

TSH directly stimulate D2 deiodinase which controls T4 -> T3 conversion. As overall output from the thyroid begins to decline, the pituitary can compensate by increasing TSH production to not only direct increased thyroid hormone production, but also to maintain circulating T3 by increasing D2 activity, and thus peripheral T4 -> T3 conversion. This situation may manifest as moderate-high fT3, but a barely in-range fT4 and total T4, with a slightly elevated TSH between 2.5 - 4. However, although circulating T3 levels are maintained, there are various cells which rely solely on the uptake of T4 for local conversion to T3 rather than the direct uptake of T3 itself, which is why maintaining an optimal total and fT4 is extremely important, despite T4 itself being a largely inactive hormone — this is especially true for cells in the CNS.

My own thyroid panel has always fit the above, and my body temps, heart rate and other hypothyroid symptoms respond strongly to taking thyroid hormone, despite all my labs being within range, and fT3 being 'optimal'. Unfortunately, I struggle to tolerate thyroid hormone long-term as it causes my cortisol to drop below range which produces extremely severe symptoms, and subsequently the forced cessation of thyroid. Low cortisol is often associated with hypothryoidism as the adrenals themselves require adequate thyroid hormone for cholesterol -> pregnenolone conversion, and thus the production of their own hormones.

I'm hoping some combination of thyroid + hydrocortisone and/or pregnenolone and/or progesterone will allow me to make progress in addressing my hypothyroid symptoms, but there is still a lot of experimentation needed.

Also good T3 levels help your cholesterol levels, especially your LDL cholesterol.

 

[JoeMatts]

Also good T3 levels help your cholesterol levels, especially your LDL cholesterol.

Indeed. Before the development of the thyroxine blood test, cholesterol levels were used as an indirect biomarker of low thyroid function, as T3 controls the rate of systemic cholesterol -> pregnenolone production, among other cholesterol-derived substances. Unfortunately most physicians have discarded this fact, so when a patient on T4 monotherapy with lingering hypothryoid symptoms presents with elevated cholesterol, they proceed to prescribe a statin, instead of revaluating their thyroid treatment— a very sad state of affairs.

 

[trtthings]

Anecdotally, my hypothyroid symptoms - low body temps and pulse, fatigue, dry skin, digestive issues, etc - have always correlated with my fT4 and total T4, even when fT3 was top of the range, and TSH was within range, but slightly elevated. These symptoms started following an extended period of severe caloric restriction, prolonged fasting and excessive exercise — all of which are suppressive to thyroid function on various levels.

TSH directly stimulates D2 deiodinase which controls T4 -> T3 conversion. As overall output from the thyroid begins to decline, the pituitary can compensate by increasing TSH production to not only direct increased thyroid hormone output, but also to maintain circulating T3 by increasing D2 activity, and thus peripheral T4 -> T3 conversion. This situation may manifest as moderate-high fT3, but a barely in-range fT4 and total T4, with a slightly elevated TSH between 2.5 - 4. However, although circulating T3 levels are maintained, there are various cells which rely solely on the uptake of T4 for local conversion to T3 rather than the direct uptake of T3 itself, which is why maintaining an optimal total and fT4 is extremely important, despite T4 itself being a largely inactive hormone — this is especially true for cells in the CNS, as T4 crosses the blood-brain-barrier more readily than T3; google 'hyperthyroid dementia' which can result from high-dose T3 monotherapy suppressing systemic T4 levels for more information.

My own thyroid panel has always fit the above, and my body temps, heart rate and other hypothyroid symptoms respond strongly to taking thyroid hormone, despite all my labs being within range, and fT3 being 'optimal'. Unfortunately, I struggle to tolerate thyroid hormone long-term as it causes my cortisol to drop below range which produces extremely severe symptoms, and subsequently the forced cessation of treatment. Low cortisol is often associated with hypothryoidism as the adrenals themselves require adequate thyroid hormone for cholesterol -> pregnenolone conversion, and thus the production of their own hormones.

I'm hoping some combination of thyroid + hydrocortisone and/or pregnenolone and/or progesterone will allow me to make progress in addressing my hypothyroid symptoms, but there is still a lot of experimentation needed.

Interesting to hear, what were your primary symptoms before getting on TRT?

 

[JoeMatts]

Interesting to hear, what were your primary symptoms before getting on TRT?

All the standard things — low energy, exercise intolerance, morning fatigue, inability to build muscle mass, brain fog, low sex drive and regular ed. TRT didn't do anything to improve any of the above apart from increased muscle mass; it actually made many of them worse due the adrenal-suppression it produced, though I acknowledge not everybody experiences that as a by-product of exogenous testosterone. I've had much more success pursuing the adrenal and thyroid route in terms of symptom resolution, but I'm considering re-starting trt in the future in the form of low-dose, daily injections of a proprionate / enanthate blend that's been discussed here recently.

 

[trtthings]

All the standard things — low energy, exercise intolerance, morning fatigue, inability to build muscle mass, brain fog, low sex drive and regular ed. TRT didn't do anything to improve any of the above apart from increased muscle mass; it actually made many of them worse due the adrenal-suppression it produced, though I acknowledge not everybody experiences that as a by-product of exogenous testosterone. I've had much more success pursuing the adrenal and thyroid route in terms of symptom resolution, but I'm considering re-starting trt in the future in the form of low-dose, daily injections of a proprionate / enanthate blend that's been discussed here recently.

Can you elaborate on the suppression you've experienced? Which markers have you been measuring? Would be interested to see your blood tests.

My primary symptom was pronounced fatigue which testosterone does help with. I've been measuring cortisol as well as FT3 and FT4 for fun lately too.

 

[JoeMatts]

Can you elaborate on the suppression you've experienced? Which markers have you been measuring? Would be interested to see your blood tests.

My primary symptom was pronounced fatigue which testosterone does help with. I've been measuring cortisol as well as FT3 and FT4 for fun lately too.

The trt-induced adrenal suppression involved below range serum am cortisol, low four-point saliva cortisol across the day, undetectable progesterone and below-range DHEA-S — all of which return to normal following the cessation of testosterone. Taking thyroid hormone has a similar suppressive effect though not as severe, so it might not be solely related to testosterone (I believe testosterone's suppressive effect on both the release and action of ACTH is heavily involved, however).

Anecdotally, 2.5 - 5 mg of hydrocortisone upon waking causes the fatigue to immediately dissipate, but hydrocortisone supplementation isn't something I'm interested in pursuing long-term.

Consider testing total T4 and T3 instead of free, as they always better correlated with my symptoms; the 'free hormone' hypothesis has various flaws.

 

[trtthings]

The trt-induced adrenal suppression involved below range serum am cortisol, low four-point saliva cortisol across the day, undetectable progesterone and below-range DHEA-S — all of which return to normal following the cessation of testosterone. Taking thyroid hormone has a similar suppressive effect though not as severe, so it might not be solely related to testosterone (I believe testosterone's suppressive effect on both the release and action of ACTH is heavily involved, however).

Anecdotally, 2.5 - 5 mg of hydrocortisone upon waking causes the fatigue to immediately dissipate, but hydrocortisone supplementation isn't something I'm interested in pursuing long-term.

Consider testing total T4 and T3 instead of free, as they always better correlated with my symptoms; the 'free hormone' hypothesis has various flaws.

Interesting to hear, but do you not find that your FT3 and FT4 correlate with your total T3 and T4? If they don't then surely your TBG is varying a great deal?

 

[JoeMatts]

Interesting to hear, but do you not find that your FT3 and FT4 correlate with your total T3 and T4? If they don't then surely your TBG is varying a great deal?

Not really. Never looked at TBG as it's a pointless test, but total T4 has always been extremely low despite free t4 / 3 being somewhat normal. Raising total T4 with levothyroxine and low-dose T3 always causes a significant increase in body temp and overall wellbeing until cortisol levels drop too low. It's also the only thing that lowers my elevated prolactin; elevated prolactin is associated with hypothyroidism.

 

[trtthings]

Not really. Never looked at TBG as it's a pointless test, but total T4 has always been extremely low despite free t4 / 3 being somewhat normal. Raising total T4 with levothyroxine and low-dose T3 always causes a significant increase in body temp and overall wellbeing until cortisol levels drop too low. It's also the only thing that lowers my elevated prolactin; elevated prolactin is associated with hypothyroidism.

How elevated is your prolactin? Not enough to check for an adenoma I guess?

Interesting to hear. I would consider thyroid replacement myself, and/or low-dose hydrocortisone but it just sounds like a pain to titrate that and find an optimal dose. Looking at people on thyroid replacement they often have to change the dosage even with the seasons.

However if I recall some people (including John Crisler) claim that hydrocotisone is not suppressive at low doses. Up to 20mg daily iirc.

Do you take an SSRI by any chance?

 

[JoeMatts]

How elevated is your prolactin? Not enough to check for an adenoma I guess?

Interesting to hear. I would consider thyroid replacement myself, and/or low-dose hydrocortisone but it just sounds like a pain to titrate that and find an optimal dose. Looking at people on thyroid replacement they often have to change the dosage even with the seasons.

However if I recall some people (including John Crisler) claim that hydrocotisone is not suppressive at low doses. Up to 20mg daily iirc.

Do you take an SSRI by any chance?

Prolactin is very elevated, but it's always in-response to testosterone and hcg, so it's primarily mediated by an increased is systemic estrogenic load.

You are correct that thyroid and adrenals are hard to treat in terms of practicality, but that doesn't bother me too much because impaired thyroid function is heavily implicated in heart disease, cancer, various brain diseases, etc, so treatment goes well beyond just feeling better. Thyroid itself is straightforward - start small, increase dose every two to four weeks using basal body temperature, symptoms and labs as barometers - but the main issues arise when the adrenal response does not rise accordingly to support an increased metabolic rate.

Theoretically thyroid + pregnenolone and/or progesterone should fill the need for hydrocortisone, but you can definitely use low doses without risk of long-term suppression. Regardless, the implications of HPTA shutdown are much more serious than that of the HPTA, so it's not worth messing with unless the adrenals are destroyed imo (which mine aren't; I had a strong adrenal response to 250mcg tetracosactrin). Also, supplemental cortisol covers up the symptoms but does nothing to address the underlying reason as to why cortisol is low, which is another downside to consider.

Have never and would never touch any substance that directly increases serotonin, including SSRI's, but also 5-HTP, l-trypophan, certain herbs, etc. There's little evidence to support the 'happy hormone' label big pharma has placed on serotonin, whereas there's an abundance of data to support the opposite — the fact that it increases alongside estrogen, prolactin, cortisol, and other mediators of the stress system is telling. Interesting read for those interested:

Is serotonin an upper or a downer? The evolution of the serotonergic system and its role in depression and the antidepressant response

 

[trtthings]

Prolactin is very elevated, but it's always in-response to testosterone and hcg, so it's primarily mediated by an increased is systemic estrogenic load.

You are correct that thyroid and adrenals are hard to treat in terms of practicality, but that doesn't bother me too much because impaired thyroid function is heavily implicated in heart disease, cancer, various brain diseases, etc, so treatment goes well beyond just feeling better. Thyroid itself is straightforward - start small, increase dose every two to four weeks using basal body temperature, symptoms and labs as barometers - but the main issues arise when the adrenal response does not rise accordingly to support an increased metabolic rate.

Theoretically thyroid + pregnenolone and/or progesterone should fill the need for hydrocortisone, but you can definitely use low doses without risk of long-term suppression. Regardless, the implications of HPTA shutdown are much more serious than that of the HPTA, so it's not worth messing with unless the adrenals are destroyed imo (which mine aren't; I had a strong adrenal response to 250mcg tetracosactrin). Also, supplemental cortisol covers up the symptoms but does nothing to address the underlying reason as to why cortisol is low, which is another downside to consider.

Have never and would never touch any substance that directly increases serotonin, including SSRI's, but also 5-HTP, l-trypophan, certain herbs, etc. There's little evidence to support the 'happy hormone' label big pharma has placed on serotonin, whereas there's an abundance of data to support the opposite — the fact that it increases alongside estrogen, prolactin, cortisol, and other mediators of the stress system is telling. Interesting read for those interested:

Is serotonin an upper or a downer? The evolution of the serotonergic system and its role in depression and the antidepressant response

Was wondering because serotonin increases prolactin. However there exist antidepressants (that aren't SSRIs) that don't have that effect. But alright, very elevated still sounds like something to look into. Do you take an AI to control it/see a difference from taking an AI?

And if you're intent on treating the thyroid, but not willing to take hydrocortisone, what's your alternative plan, is it to take pregnenolone? I've tried the tablets myself a couple of times, I felt like they made me more emotional both times (not desirable for me). However some people like John Crisler advocated taking the cream instead. I'm not sure what he was basing that on. He was also adamant that you shouldn't supplement with progesterone as it had feminizing effects, I'm wondering if that's why I felt like I did with the pregnenolone (or if it was just that my estradiol was out of check).

 

[JoeMatts]

Was wondering because serotonin increases prolactin. However there exist antidepressants (that aren't SSRIs) that don't have that effect. But alright, very elevated still sounds like something to look into. Do you take an AI to control it/see a difference from taking an AI?

And if you're intent on treating the thyroid, but not willing to take hydrocortisone, what's your alternative plan, is it to take pregnenolone? I've tried the tablets myself a couple of times, I felt like they made me more emotional both times (not desirable for me). However some people like John Crisler advocated taking the cream instead. I'm not sure what he was basing that on. He was also adamant that you shouldn't supplement with progesterone as it had feminizing effects, I'm wondering if that's why I felt like I did with the pregnenolone (or if it was just that my estradiol was out of check).

Crisler recommended transdermal over oral because it skips the first pass of the liver, which is responsible for much of the pregnenolone -> progesterone conversion; transdermal skips the first pass, seemingly increasing preg sulfate and the androgens more than prog and the progestins. Regardless, Crisler demonized prog purely on the basis that it's 'femininizing', which whilst true in excess, does not mean that men don't need optimal levels, nor does it mean maintaining levels within the physiological range for a healthy male will produce feminization. What dose of oral pregnenolone did you take? Some theorize that non-extended release forms can cause issues due to the sudden spike / drop from it's short half-life, so perhaps you could try a brand like nutricology. There are studies that show doses above 10mg can increase progesterone disportionately to the androgens, which may have been your issue. Conversely, there are many people on trt who see no increase at all in progesterone from preg (this was the case for me, presumably from HPTA-induced downregulation of specific enzymes in the steroid hormone cascade), or who find that pregnenolone supplementation produces side effects that are not repeated by taking progesterone directly, so your reaction could have just been something specific to the preg.

As far as how I plan to go about increasing cortisol: it'll probably be with some combination of preg, prog and dhea with thyroid. The ability of the adrenals to produce cortisol is thyroid-dependant, as T3 is required to drive cholesterol -> pregnenolone conversion in the mitochondria - and thus the production of all downstream steroids - which is why chronic, unaddressed hypothyroidism will usually lead to low cortisol, prog, dhea, testosterone, etc. Paradoxically, thyroid hormone requires the presence of the adrenal hormones to exert its own action, so trying to restore either one without the other is often unsuccessful. The key distinction here is that we're trying to restore the bodies ability to produce its own hormone, but taking hydrocortisone does the exact opposite by suppressing CRH/ACTH, and by-proxy, further inhibiting the body's own production of cortisol, preg, prog, dhea and their associated metabolites. Pregnenolone can serve as substrate upstream for cortisol without causing suppression to the HPA, but it also has many of its own actions independent of the conversion to cortisol that aid the body in supporting the increased thyroid function required to restore adrenal steroidogenesis.

In my view, the elevated prolactin is secondary to hypothyroidism and the associated increase in estrogen / serotonin it produces (thyroid function determines the rate at which estrogen is glucuronidated and subsequently excreted), so addressing it directly isn't something I'll be pursuing. I don't take trt anymore, but when I did, an aromatase inhibitor would reduce my prolactin as expected. However, this never produced the improvements in symptomatology that I'd have hoped, and I believe this is because the underlying physiological state that leads to one being prone to an excess of aromatization is more problematic than the absolute amount of estrogen, which is merely the manifestation, and not the problem itself. I don't deny that aromatase inhibitors do help some people, but very rarely are they the difference between feeling like shit and feeling 100% — which is expected, given the aforementioned. Aromatase inhibitors also have many issues of their own, some of which that go beyond solely the inhibition of aromatase.

I could be wrong, but addressing anything other than thyroid function (and also trying to identify the exact reason why thyroid function is impaired along with taking supplemental thyroid) is not addressing the real issue.

 

[trtthings]

Crisler recommended transdermal over oral because it skips the first pass of the liver, which is responsible for much of the pregnenolone -> progesterone conversion; transdermal skips the first pass, seemingly increasing preg sulfate and the androgens more than prog and the progestins. Regardless, Crisler demonized prog purely on the basis that it's 'femininizing', which whilst true in excess, does not mean that men don't need optimal levels, nor does it mean maintaining levels within the physiological range for a healthy male will produce feminization. What dose of oral pregnenolone did you take? Some theorize that non-extended release forms can cause issues due to the sudden spike / drop from it's short half-life, so perhaps you could try a brand like nutricology. There are studies that show doses above 10mg can increase progesterone disportionately to the androgens, which may have been your issue. Conversely, there are many people on trt who see no increase at all in progesterone from preg (this was the case for me, presumably from HPTA-induced downregulation of specific enzymes in the steroid hormone cascade), or who find that pregnenolone supplementation produces side effects that are not repeated by taking progesterone directly, so your reaction could have just been something specific to the preg.

As far as how I plan to go about increasing cortisol: it'll probably be with some combination of preg, prog and dhea with thyroid. The ability of the adrenals to produce cortisol is thyroid-dependant, as T3 is required to drive cholesterol -> pregnenolone conversion in the mitochondria - and thus the production of all downstream steroids - which is why chronic, unaddressed hypothyroidism will usually lead to low cortisol, prog, dhea, testosterone, etc. Paradoxically, thyroid hormone requires the presence of the adrenal hormones to exert its own action, so trying to restore either one without the other is often unsuccessful. The key distinction here is that we're trying to restore the bodies ability to produce its own hormone, but taking hydrocortisone does the exact opposite by suppressing CRH/ACTH, and by-proxy, further inhibiting the body's own production of cortisol, preg, prog, dhea and their associated metabolites. Pregnenolone can serve as substrate upstream for cortisol without causing suppression to the HPA, but it also has many of its own actions independent of the conversion to cortisol that aid the body in supporting the increased thyroid function required to restore adrenal steroidogenesis.

In my view, the elevated prolactin is secondary to hypothyroidism and the associated increase in estrogen / serotonin it produces (thyroid function determines the rate at which estrogen is glucuronidated and subsequently excreted), so addressing it directly isn't something I'll be pursuing. I don't take trt anymore, but when I did, an aromatase inhibitor would reduce my prolactin as expected. However, this never produced the improvements in symptomatology that I'd have hoped, and I believe this is because the underlying physiological state that leads to one being prone to an excess of aromatization is more problematic than the absolute amount of estrogen, which is merely the manifestation, and not the problem itself. I don't deny that aromatase inhibitors do help some people, but very rarely are they the difference between feeling like shit and feeling 100% — which is expected, given the aforementioned. Aromatase inhibitors also have many issues of their own, some of which that go beyond solely the inhibition of aromatase.

I could be wrong, but addressing anything other than thyroid function (and also trying to identify the exact reason why thyroid function is impaired along with taking supplemental thyroid) is not addressing the real issue.

So did you give up on TRT due to symptoms? Excess aromatisation/anxiety/irritability/depression/something else?

How long did you give it before quitting and with what level of AI if any?

Edit: Also you're aware that E2 suppresses T4 -> T3 conversion, and that inflammation suppresses the thyroid and increases aromatisation, whereas testosterone decreases many inflammatory markers?

I haven't heard the case of TRT crashing cortisol before though. Personally I believe my issue is primarily an issue with inflammation (and possibly the immune system). I had fatigue that was absolutely wrecking me before TRT and I feel best with TRT and adequate AI with regard to that.

 

[trtthings]

@JoeMatts

Had another blood test drawn today where FT4 came back at 12.8 pmol/l (range 10.5 - 24.5). I've had two before with 15.1 and 15.8. I'm not too thrilled about how low it is but I'm also very hesitant to intervene with that.