- Apr 2021
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www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
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In seven out of the eleven subjects in whom core body temperature could be sampled, the nadir of body temperature was advanced during L-T4 intake by 15 minutes to 270 minutes.
This supports my speculation from another study, found here.
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- Apr 2020
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www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
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RESULTS: The rate of discontinuation due to side effects was significantly higher in the control group than for the patients (38% versus 0%). The severity of the side effects in the controls increased significantly during treatment with T(4). The side effect scores of the patients were higher than those of the controls prior to T(4) treatment, but did not change significantly during the treatment period. Although the serum concentrations of thyroid hormones rose significantly in both groups, concentrations of fT(3) and fT(4) were significantly higher in the controls.CONCLUSIONS: Healthy controls and depressed patients respond significantly differently to supraphysiological T(4). Healthy controls experience higher elevations of thyroid hormones in response to supraphysiological T(4), thus inducing significantly more side effects and discontinuation.LIMITATIONS: Open-label study; groups were studied at different times; in contrast to healthy controls, depressed patients were also taking antidepressants.
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.
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- Mar 2020
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www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
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The addition of supraphysiologic doses of L-T4 (300 mcg per day) to an otherwise stable medication regimen of standard treatments resulted in a significant decline in depression scores during the 6-week, double-blind treatment phase. At endpoint (week 6), the mean HamD score showed a group difference of 3.7 points in favor of L-T4. Such difference is generally considered to be clinically meaningful in a short-term treatment trial for major depression. NICE used a 3.0-point difference in HamD change scores as a criterion of clinical significance.27
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.
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www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
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L-thyroxine at an average dose of 350 micro g/die. Outcomes were moderate in 39.3% and very good in 21.5%, corresponding to 21-item HAMD scores of < or =16 and < or =8 and clinical judgement. Of all patients, 39.3% had to stop treatment due to nonresponse or side effects.
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).
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- Feb 2020
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www.hindawi.com www.hindawi.com
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Surprisingly, treatment with supraphysiological doses of L-T4 did not cause significant effects on sleep architecture. However, the increase in body movements and REM density was close to reaching statistical significance.
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.
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www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
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At the time of assessment, patients had been treated with supraphysiological T4 (mean dose 368 microg/d) for a mean of 54 months. The total subjective response score was +25.2.
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).
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- Jan 2020
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www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
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RESULTS: Two patients dropped out of the study owing to side effects. The remaining 7 patients received a final mean dose of T4 of 235 +/- 58 micrograms/day (range: 150-300 micrograms/day). Their scores on the Hamilton Depression Rating Scale had fallen from a mean of 21.1 +/- 4.1 before inclusion in the study to a mean of 8.0 +/- 2.8 at the end of the 8th week. Five patients were full responders, 1 a partial responder, and 1 a nonresponder.CONCLUSIONS: Augmentation with high-dose T4 proved to have an antidepressant effect in more than 50% of the previously treatment-resistant patients with chronic depression and/or dysthymia.
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.
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Thyroxine was added to their antidepressant medication, and the doses were increased to a mean of 482 ± 72 μg/day.
This is the highest dose of levothyroxine that I've seen administered. Even treatment for thyroid cancer rarely goes beyond 300 mcg (or even 200 mcg, which is more common).
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www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
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(A)–(C) Changes in markers of thyroid status over the course of the study (mean ± standard error). (D) Changes in treatment preference.
Looks like preference for T3 increased as the number of hyperthyroid symptoms increased. It would be interesting to know if those are the same patients.
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www.drugwiki.net www.drugwiki.netCytomel1
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L-T3 has proven to be 4-5 times more biologically active and to take effect more quickly than L-thyroxine (L-T4).
Will need to check up on that. I recall T4 being less potent.
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www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
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Following this observation, the same group conducted a cross-sectional analysis to assess the association among 140 patients with EE and TH replacement hypothyroid treated with LT4. In this study population, REE did not differ significantly between patients achieving low-normal (TSH ≤ 2.5 μIU/mL) vs high normal TSH (TSH >2.5 μIU/mL). Conversely, free T3 level showed a direct correlation with EE, but also with indices of adiposity including body mass index (BMI), body composition, and fat free mass [49]. This latter observation is consistent with other cross-sectional studies that have clearly defined the positive association between circulating levels of T3 and adiposity [50, 51].
This is consistent with my previous assertion that T3 may result in greater energy expenditure than T4.
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The authors demonstrated an inverse correlation between TSH and REE with a change of 15% for a TSH ranging from 0.1 to 10 μIU/mL. Of interest, free T4 remained within the normal range in all of the study volunteers. Nonetheless, the changes in REE with different LT4 doses were demonstrated in every patient [46].
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.
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www.encognitive.com www.encognitive.com
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0.19
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.
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- Aug 2018
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www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
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AbstractHigh dose thyroid hormone has been in use since the 1930s for the treatment of affective disorders. Despite numerous papers showing benefit, the lack of negative trials and its inclusion in multiple treatment guidelines, high dose thyroid has yet to find wide spread use. The major objection to the use of high dose thyroid is the myth that it causes osteoporosis. This paper reviews the literature surrounding the use of high dose thyroid, both in endocrinology and in psychiatry. High dose thyroid does not appear to be a significant risk factor for osteoporosis while other widely employed psychiatric medications do pose a risk. Psychiatrists are uniquely qualified to do the risk-benefit analyses of high dose thyroid for the treatment of the bipolar I, bipolar II and bipolar NOS. Other specialties do not have the requisite knowledge of the risks of alterative medications or of the mortality and morbidity of the bipolar disorders to do a full risk benefit analysis.
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
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- Apr 2018
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www.wilsonssyndrome.com www.wilsonssyndrome.com
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There was a boy who was born with congenital hypothyroidism and was raised on traditional T3 (Cytomel). He was never treated with a T4-containing medicine, and so essentially never had a molecule of T4 in his body. By age 26 he had developed normally with no problems.
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.
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