The American Thyroid Association mentions otherwise, so which is it?

same bioavailability between desiccated thyroid and synthroid

desiccated thyroid is basically the crushed up thyroid gland from an animal

Three factors leading to LT4 becoming the predominant choice of therapy in hypothyroidism

Conversion table available in thyroid (dessicated thyroid) monograph for the commercially available products. Compounding pharmacies can prepare custom dosing for your specific needs

Still, there was no difference in thyroid function blood test and psychometric test (for cognitive functioning) results

Results for the study appear to show benefit for dessicated thyroid compared to synthroid, both for patient preference and for extent of weight loss

Some people get a better response with desiccated thyroid than with synthroid

So desiccated thyroid was before synthroid

GeneName: DICER1 PMCID: PMC7859642 HGNCID: Unavailable Inheritance Pattern: Autosomal dominant. Disease Entity: Familial pleuropulmonary blastoma (PPB), cervix embryonal rhabdomyosarcoma, multinodular goiter, nasal chondromesenchymal hemartoma, Ciliary body medulloepithelioma, Sertoli-Leydig Cell Tumor (SLCT), differentiated thyroid carcinoma, pituitary blastoma, pineoblastoma, cystic nephroma, Wilm's tumor and sarcomas of different sites including, amongst others, the uterine cervix, kidney and brain. Mutation: Germline Zygosity: Heterozygose Variant: No ClinVarID present. Family Information: No family outline Case: No specified information of patients included. CasePresentingHPO's: n/a CasePrevious Testing: n/a gnomAD: n/a Mutation Type: nonsense, frameshift, or splice affected.

Gene Name: DICER1 PMID:33552988 HGNCID: Unavailable Inheritance Pattern:Autosomal Dominant Disease Entity: familial pleuropulmonary blastoma (PPB),cystic nephroma, ovarian Sertoli-Leydig cell tumor (SLCT), multinodular goiter, cervix embryonal rhabdomyosarcoma, Wilms’ tumor, nasal chondromesenchymal hamartoma, ciliary body medulloepithelioma, differentiated thyroid carcinoma, pituitary blastoma, pineoblastoma, and sarcomas of different sites. Mutation: Nonsense, Frameshift<br /> Zygosity: Heterosygosity Variant:No ClinVar ID present Family Information:no diseases mentioned in family Case: no specified case in this article gnomAD: n/a Mutation type: Nonsense. frameshift

GeneName: DICER1 PMID: 28323992 PMCID: PMC5443331 *No HGNCID found Inheritance pattern: autosomal-dominant Disease Entity: multinodular goiter and thyroid cancer Mutation: Germline Zygosity: not listed Variant: c.3726C>A; p.Tyr1242a, c.3675C>G; p.Tyr1225a Family Information: 145 individuals with DICER1 germline mutations from 48 family controls (135 individuals) that lacked the DICER1 mutation Case: male and female carriers as well as family members were studied. Ages: 20, 30, and 40 for both populations (DICER1 carriers were significantly younger than controls}. Population from Great Britain, UK, and USA (no significant difference between race, ethnicity, or sex found). CasePresentingHPOs: no previous therapeutic radiation or chemotherapy. Thyroid cancer or MNG diagnoses were likely reported with the DICER1 mutation CasePreviousTesting: Sequencing performed with Sanger or next-generation sequencing assays. DICER1 carriers underwent testing to obtain thyroid-stimulating hormone, thyroxine, thyroxine-binding globulin, and serum albumin levels as well as medical history and physical examinations (+thyroid palpation). Participants were also given thyroid US examinations. gnomAD: n/a Mutation Type: missense

GENENAME: DICER1 PMID: 31952842 HGNCID: NONE DISEASE ENTITY: THYROID DISEASE AND OVARIAN TUMORS ZYGOSITY: HETEROZYGOUS VARIANT: NONE CASE PRESENTING HPOS: cervical embryonal rhabdomyosarcoma CASE PREVIOUS TESTING: GYNECOLOGIC HISTORY MUTATION: DELETION

This confirms that thyroid function probably lacks any (direct) effect sleep. Of course, not this evidence alone, but rather this combined with "Effects of Supraphysiological Doses of Levothyroxine on Sleep in Healthy Subjects: A Prospective Polysomnography Study"

This supports my speculation from another study, found here.

Brilliant study. Astonishingly, ~500 mcg thyroxine only increased FT3 about 20% in depressed patients. In controls, it nearly doubled FT3 (about 80# increase), Thyroxine doubled total T4 and total T3 in both depressed and controls. That lines up with the FT3 rise in controls, but is still much lower than I'd expect from this dose.

Note that the depressed patients had equal thyroid symptoms before taking thyroxine, so experienced no increase. The pre-treatment depressed patients, treated depressed patients, and treated controls all had an equal number of thyroid symptoms. Thus, only the pre-treatment healthy patients lacked hyperthyroid symptoms. This is interesting because the treatment was 500 mcg thyroxine (average 484 mcg), which you'd expect to cause more symptoms.

This could mean either that the depressed patients had as many symptoms alleviated as they had caused by thyroxine, or that depressed patients simply had lower thyroidergic activity. The latter is supported by the fact that free T3 and free T4 rose 2 or 3 times less in treated depressed patients compared to treated controls (from full text).

It's also possible that the pre-existence of symptoms masked their appearance (in which case increased severity might be expected). I doubt that this is the case. A few symptoms trended toward improvement.

The individual change in REE to a given change in dose varied radically. The dose change was only 50 mcg, which seemed to change TSH about half what they've calculated for 15% REE change. That is to say, it looks like a 50 mcg dose reduction will only raise TSH from 1.0 to 5.0, not to 10.0. This is my personal guesstimate, and will need to be properly calculated from other studies. My point is merely that 50 mcg will not cause the full 15% REE increase. Additionally, the response to 50 mcg may depend on initial TSH.

It looks like TSH changes that remained hyperthyroid (i.e. bellow 1.0) had little effect on REE. This might be because the body is maintaining thyroid status, or that REE is more like an on/off switch. However, this only covers relatively small changes in thyroxine dose.

It is unclear how supraphysiological doses effect REE. It seems likely that the ten times greater dose (500 mcg) used for depression would significantly increase REE.

This suggests that hypothyroidism shortens the circadian cycle, while hyperthyroidism does nothing. This is disappointing, and also counter to what I expected. However, it could still be consistent with my expectations if these effects are behaviorally mediated. That is to say, it could be greater stimulation that keeps them awake longer (which in turn effects the body clock). If that is the case, the alertness/dullness effects could be countered by depressants/stimulants, which would reveal the direct circadian impact.

Additionally, I'd like to know if T3 doses at wake time could provide any entrainment (or at night time). The half life of T3 is short enough that reveal phase effects. T4 only demonstrates net effects; like getting light exposure all day long, T4 may both delay and advance circadian phase.

Also note that all conditions have a distinct rightward tilt when graphed. That is to say, they have a body clock longer than 24 hours. It's quite plausible that the thyroid hormone could interact with zeitgebers.

This is the same dosage that another study found to be indiscernible from placebo. I suspect a couple things are at play.

The first is that these are treatment-resistant patients, meaning that we already know they are not susceptible to placebo; given that we are effectively comparing combination therapy to SSRIs alone, this means that the SSRI only stage is not experiencing placebo, thus making the therapeutic effect visible by comparison (retrospective comparison, given that there is no control group).

The second is that this is combination therapy. It seems likely that thyroxine is more effective when combined with SSRIs.

Note that this study uses much lower doses than similar studies I've seen, yet had similar results in terms of efficacy rate (roughly 50% responders). I'm not currently certain how the magnitude of effects compares with those studies. Namely, comparing with Pfeiffer et al (350 mcg), Rudas et al (235 mcg) and Bauer et al (482 mcg), and also Bauer et al from 2016 (300 mcg)

This is consistent with the open label data. The dose is also similar. Combining this placebo-controlled trial with the three open-label supraphysiological thyroxine studies that I've seen, that is sufficient for me to conclude efficacy. Namely, combining with Pfeiffer et al (350 mcg), Rudas et al (235 mcg) and Bauer et al (482 mcg)

I would like to see if this study mentions nonresponders. Those three other studies found roughly a 50% response rate. Thus, the effect size in responders may be twice as significant.

1.5 mcg/kg comes to 102 mcg per 150 pounds. That's lower than I'd expected.

This is another study consistent with the 50% remission figure. The dose is also similar: between 235 mcg (Rudas et al) and 482 mcg (Bauer et al).

These make good reference figures. Given that normal T3 values are around 100 ng/dL, Graves' patients had 2 to 7 times normal levels. This is good because it means the symptoms associated with hyperthyroidism may be only on the upper end. Supraphysiological therapeutic doses of T4 (500 mcg) are only 3 or so times the full replacement dose.

T3 values in painless thyroiditis were only 1 to 3 times normal, except for 1 outlier. Thus, I would predict few symptoms in painless thyroiditis.Or, perhaps, symptoms only in few patients.

It appears that the liothyronine could have advanced the phase of circadian temperature. However, since the study had no controls, it is impossible to confirm this hypothesis.

It appears they are calculating based on total T3 rather than added T3. Assuming that the conversion of T4 to T3 remains constant, the half life of the liothyronine dose towards baseline is less than 10 hours (I'd estimate 5-7 hours). Given that this is short compared to other studies, it is likely that the conversion was slowed by the high thyroid status.

Fascinating. At 100 mcg, I'd expect one to be able to tell the difference. This is especially surprising given the two groups. Namely, the symptomatic group and the healthy control group. I'd expect at least one group to be able to tell the difference. However, it's worth noting that the TSH between the two groups were virtually identical. The groups were selected based on hypothyroid symptoms rather than actual thyroid status.

The fact that healthy controls could not tell the difference is odd. It is both not what I expected and cuts against what the related lesswrong article says about discernibility to healthy subjects (odd given that lesswrong mentions this specific study). What may be happening is that the question was not specific enough. If subjects interpreted reduced vitality as a sign that they were not receiving thyroxine, then many might get is wrong. I wish they has a more thorough questionnaire on perception of drug effects. Even an informal "describe the experience" question would be nice.

All in all, I find it unlikely that this is accurate. There are at least two possibilities. It could indicate that the dose was not high enough, in which case the study is not testing what it thinks it's testing. That is supported the the fact that the TSH of the thyroxine group is barely out of the normal range. The other option, as mentioned above, is that they are not asking the right questions. If that is the case, that also seems to invalidate the findings.

In conclusion, this result means that we can't trust the study. I'm certain higher doses would be discernable from placebo to subjects. It is likely that it was discernible at this dose (100 mcg) if the right questions were asked. I'm thankful they included this outcome.

P.S. I found this study completely by accident, then found out it was related to that lesswrong article that I've always appreciated.

This is very interesting to note. This is some of the most direct evidence that hyperthyroidism shares some symptoms with hypothyroidism. I'd still like to know if liothyronine (T3) would show the same results. I suspect T3 would be better, especially given that it may be less likely to disturb sleep (because of the half life).

This is just as I expected, though I'd also be unsupervised by opposite findings. I'm yet to find why symptoms such as insomnia are so often cited for hyperthyroidism. I see a few possibilities. One is that it's very slow onset effect that takes more than 2 months to develop (personally, this seems unlikely). Another is that it only effects people with preexisting anxiety or hyper-arousal (strikes me as a likely partial explanation). A third is that it only effects people with the most extreme hyperthyroidism (also strikes me as partial explanation). Finally, it's possible that the entire thing is a myth. Authors of another study from 2011 noted that "[sleep] is being characterized as poor without further elaboration." I think it may be the case that people are just assuming patient's sleep issues are caused thyrotoxicosis because it seems like it would, when in fact only a small fraction actually are. Perhaps thyrotoxicosis even turns depressive insomnia into anxious insomnia, thereby confusing physicians.

The next question is whether treating light to moderate hyperthyroidism would resolve insomnia. This would answer some of the above possibilities. However, I'm uninterested in severe hyperthyroidism because it is above the maximum treatment dose I commonly see, namely 500 mcg thyroxine.

25.2 out of 33 is quite high (i.e. very positive results). In fact, those results seem too good to be true, and are likely due to the limitations of the study. In particular, by 54 months of treatment the non-responders or those with side effects would have already stopped taking thyroxine. Nonetheless, the data is consistent with other studies indicating that supraphysiological doses of levothyroxine has few and mild side effects (regardless of the sample population).

Thyroxine working in about 50% of patients was also found in Bauer et al. This dose was not quite as high as Bauer, but 235 mcg is still above a full replacement dose.

I'd like to see results on minor depression. However, such studies are unlikely.

It appears that even mild thyroid elevation radically cuts TSH. Makes sense.

Graves disease has a average free T3 at least 3 times the upper normal range. This implies that there is only a little bit of wiggle room between high thyroid status and thyrotoxicosis. However, free T4 is at about twice as high as upper normal, so the total thyroid activity may be closer to 3.5 or 4 times the upper normal (assuming that T4 is roughly 10 times less potent than T3)

Most thyroiditis patients had total T3 in the upper reference range. Free T4, on the other hand, was nearly all above reference range. Graves' disease had half somewhat elevated and half extremely elevated levels for bot total T3 and free T4. I now just need data on free T3 (which in my recollection would be expected to scale tightly with total T3, so I may be able to predict the values).

Note that the high dose was because they were increasing the dose based on symptoms. That is to say, as the thyroid gland produced less thyroid hormone, they increased liothyronine dose to compensate.

If this holds true, I'd expect rapid blood volume expansion from thyroid hormone. I'm also interested in whether thyroid hormone stimulates the production of albumin, given its anabolic properties.

300 mcg is on the high side. Nevertheless, lack of hyperthyroid symptoms is not surprising. The highest dose administered in the Skinner study was 275 mcg, but that was merely for the elimination of hypothyroid symptoms.

It seems like doses would need to be quite high in order to become symptomatic. The only counterevidence I'm aware of so far is anecdotes I've read online. Thus, it appears that high doses are well tolerated.

If the mechanism is really the same as alpha blockers, then the blood volume expansion may be expected to be similar in constitution. However, I would expect more red blood cells in thyroid mediated volume expansion compared to alpha blockers. The reason, obviously, is because of the increased oxygen demand from thyroid hormone.

Thus, a 15% expected increase would be reasonable for a euthyroid subject such as myself. However, since T3 reduces weight compared to T4, it is possible the weight loss indicates greater energy expenditure.

So, given that thyroid hormone resistance does exist, the remaining question is whether it is common enough to explain some cases of CFS or similar conditions. Unfortunately this paper is not in english, but the abstract provides enough information to google more.

I ought read the full study to see the proposed mechanism. The vasopressin effect is not surprising at all, but the oxytocin effect was unexpected for me. That may be because I know more about vasopressin than I do oxytocin.

This is the only group with a TSH significantly below the reference range. The reason, of course, is that the patients with the most symptoms ended up getting the highest doses of thyroxine (T4) by the end of the study.

The study does not provide enough information to determine whether this is meaningful. It appears to be meaningless. If they had used a crossover design, then this might be useful.

Note that they did not have a mild hyperthyroidism group, whereas they did have a mild hypothyroidism group.

Before reading the study, I'll state that my suspected mechanism is dry skin. Hyperthyroidism causes oily skin, while hypothyroidism causes dry skin. Thus, I'd expect hypothyroidism to have similar symptoms to using harsh detergents/soap and/or scrubbing too frequently or too hard.

This is exactly what I expected to find. This is why I doubt that there is significant risk to high dose T3 taken in the morning. In fact, given that hypothyroidism is also associated with increased fracture, I'm inclined to think that thyroid hormones per se play no role whatsoever, but rather the downstream effects. That is to say, hyperthyroidism disturbs sleep, thus harming bones. I conclude, then, that so long as sleep quality is maintained, hyperthyroidism is plausibly safe for the bones.

Liothyronine does not raise blood pressure despite the rise in heart rate. The reason that respiratory rate (RR) was not changed may be because the increased cardiac output compensates for the increased oxygen demand.

The T3 half-life, therefore, is only 14.25 hours (14 hours and 15 minutes). I calculated this based on taking the peak value and comparing it to the baseline value 22 hours later.

Since they've been on the same dose during this study period, the baseline value is what's left from yesterday's peak, and can be assumed to be tomorrows trough. Since the drug took 2 hours to peak, there are 22 hours remaining to reach trough/baseline values.

This is all very interesting. It is also true that, in the treatment of depression, there is a relatively low dropout rate due to side effects from treatment with T3 (liothyronine).

liothyronine (T3) augmentation in the treatment of depression

This is precisely the type of information I was looking for. Wikipedia implied T4 should be taken with long-term T3, but the reasoning was poorly explained. However, I'd like a more official source for this case report.

This case would also express no rT3 (reverse-T3). Thus, it appears that neither T4 nor rT3 serve any vital functions.