High Dose Thyroid

[clausewitz2]

This one is for all you endocrine folks out there.

Psychiatry has been interested in using various thyroid preparations to treat a number of conditions for a very long time (like, since the late 19th century). We have good evidence that relatively small doses of T3 (like capping out at 50 mcg) can be helpful to augment treatment of depression, and actually do just as well as lithium for this purpose. That's all well and good and we're physicians enough to feel pretty comfortable about managing that sort of dosing.

There is also a camp within psychiatry, however, that advocates for much larger doses of thyroid hormone to treat depression, especially bipolar depression, and claims fairly impressive results. They have theories about subtle defects of thyroid hormone transport across cell membranes and perhaps most strikingly, they advocate for titrating doses to clinical effect/emergence of side effects and essentially ignoring TSH levels. This leads to quite high doses in some cases (like 150 mcg of T3 or 600 mcg of T4). They argue that problematic sequelae of hyperthyroidism per se may be due to the autoimmune processes usually causing an endogenous hyperthryoid state and less due to the hormone levels themselves. They point at the literature on HDT for maintaining remission of thyroid cancer and the fact that this literature does not find a great deal of evidence for the idea that exogenous thyroid hormone increases rates of osteopenia or CV difficulty.

They provide citations to papers that are not obviously low-quality, but I realize this is an argument that is not within my area of expertise. Assume for a moment it is a useful treatment for certain kinds of depression. What is the take of the endocrinologists here on the real risks of HDT that we should be looking out for and/or strong reasons why this should not be contemplated outside of true therapeutic desperation?

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[Crayola227]

@rokshana

 

[Raryn]

This one is for all you endocrine folks out there.

Psychiatry has been interested in using various thyroid preparations to treat a number of conditions for a very long time (like, since the late 19th century). We have good evidence that relatively small doses of T3 (like capping out at 50 mcg) can be helpful to augment treatment of depression, and actually do just as well as lithium for this purpose. That's all well and good and we're physicians enough to feel pretty comfortable about managing that sort of dosing.

There is also a camp within psychiatry, however, that advocates for much larger doses of thyroid hormone to treat depression, especially bipolar depression, and claims fairly impressive results. They have theories about subtle defects of thyroid hormone transport across cell membranes and perhaps most strikingly, they advocate for titrating doses to clinical effect/emergence of side effects and essentially ignoring TSH levels. This leads to quite high doses in some cases (like 150 mcg of T3 or 600 mcg of T4). They argue that problematic sequelae of hyperthyroidism per se may be due to the autoimmune processes usually causing an endogenous hyperthryoid state and less due to the hormone levels themselves. They point at the literature on HDT for maintaining remission of thyroid cancer and the fact that this literature does not find a great deal of evidence for the idea that exogenous thyroid hormone increases rates of osteopenia or CV difficulty.

They provide citations to papers that are not obviously low-quality, but I realize this is an argument that is not within my area of expertise. Assume for a moment it is a useful treatment for certain kinds of depression. What is the take of the endocrinologists here on the real risks of HDT that we should be looking out for and/or strong reasons why this should not be contemplated outside of true therapeutic desperation?

So the answer here is it is complicated.

In general terms, you need to be careful with what you define as low dose or high dose. 50mcg of T3, which is the usual studied dose in psychiatry, is a whopping dose. It may be relatively small, but that is enough thyroid hormone to be full replacement for someone who weighs 120kg. T3 is 3-4x as potent as T4 on a mcg by mcg comparison. I've seen a 55kg woman whose psychiatrist put her on the "standard" 50mcg dose who turned out borderline thyrotoxic with a suppressed TSH and had palpitations, etc. I looked at the psychiatry literature before and saw that it is the dose that is studied, but for smaller people it certainly seems inappropriately high.

Doses even higher than that though? While *some* problematic sequelae of hyperthyroidism are due to the autoimmune process (namely things like Graves ophthalmopathy), the risk of palpitations, atrial fibrillation, osteoporosis, etc are absolutely dose dependent. Even in the setting of thyroid cancer, we never push the TSH under 0.1, and the doses you're talking about will suppress the TSH of anyone.

 

[clausewitz2]

So the answer here is it is complicated.

In general terms, you need to be careful with what you define as low dose or high dose. 50mcg of T3, which is the usual studied dose in psychiatry, is a whopping dose. It may be relatively small, but that is enough thyroid hormone to be full replacement for someone who weighs 120kg. T3 is 3-4x as potent as T4 on a mcg by mcg comparison. I've seen a 55kg woman whose psychiatrist put her on the "standard" 50mcg dose who turned out borderline thyrotoxic with a suppressed TSH and had palpitations, etc. I looked at the psychiatry literature before and saw that it is the dose that is studied, but for smaller people it certainly seems inappropriately high.

Doses even higher than that though? While *some* problematic sequelae of hyperthyroidism are due to the autoimmune process (namely things like Graves ophthalmopathy), the risk of palpitations, atrial fibrillation, osteoporosis, etc are absolutely dose dependent. Even in the setting of thyroid cancer, we never push the TSH under 0.1, and the doses you're talking about will suppress the TSH of anyone.

Appreciate the response. Would you be able to point me in the direction of any literature that quantifies risks of long-term thyroid replacement at doses not chiefly designed to normalize TSH? Again, the sources I read present papers purporting to do this and pointing out flaws in other papers that they feel undermine the case against it, but I would love to have an overview that was not coming from an envangelist.

A claim have seen is that for people this is useful for clear thyrotoxic symptoms do not emerge at some of the crazier doses I mentioned above, in contrast to healthy volunteers (unfortunately often the authors and people associated with them) taking much smaller doses. I don't think they are conceptualizing it as replacement, exactly.

I bang on about this because bipolar depression is incredibly hard to treat and has a very high mortality rate, and even beyond this, impairs functioning in a way that I think is hard to appreciate for those who haven't seen it close up on a regular basis. I would like to have a clearer idea of the risks to be able to actually weigh cost v. benefit, and at the end of the day I routinely give people medications that I am fairly confident will make them diabetic and significantly more likely to experience sudden cardiac death and nobody objects to this, so "there may be medical side effects" seems inadequate.

 

[Crayola227]

darn, is rokshana the nephro person on here, and raryn the endo?

 

[Raryn]

darn, is rokshana the nephro person on here, and raryn the endo?

Both endocrine.

I don't have the time or will power to respond to the second post above at the moment, but I might get to it later. Or Rokshana might beat me to it.

 

[rokshana]

darn, is rokshana the nephro person on here, and raryn the endo?

No we are both endo...
That being said I have waited to answer here mostly due to the fact that utilizing such high doses of cytomel boggles my mind...but then I dont have experience with psych patients and the literature on utilization of T3 in that pt population.

But Raryn is right in that even in thyroid cancer pts our goals are rarely to suppress the TSH and goals in others is to normalize the TSH mostly to limit the know adverse effects of hyperthyroidism and thyrptoxicosis especially the issues of arrhythmias and osteoporosis.

Yes there are pt that develop endocrine issue due to medications that are used for treatment of other diseases...we are seeing issues of diabetes and hypophysitis with checkpoint inhibitors or thyroid issues with drugs like amiodarone that are treating life threatening arrhythmias and we work around it...the trade off of treating someone’s adrenal insufficiency with hydrocortisone is worth the increased life expectancy for someone with metastatic melanoma...or treating their diabetes if they are taking keytruda...

But in those cases, we can treat the adverse reactions to decrease the problems...but giving someone high doses of a medication to treat one issue,knowing we increase their chances of them having issues that could be life threatening? common sense tells me it’s not a good idea but I don’t have the data off the top of my head to back that up...and I’m on vacay at the moment so haven’t been checking in here as frequently

 

[clausewitz2]

No we are both endo...
That being said I have waited to answer here mostly due to the fact that utilizing such high doses of cytomel boggles my mind...but then I dont have experience with psych patients and the literature on utilization of T3 in that pt population.

But Raryn is right in that even in thyroid cancer pts our goals are rarely to suppress the TSH and goals in others is to normalize the TSH mostly to limit the know adverse effects of hyperthyroidism and thyrptoxicosis especially the issues of arrhythmias and osteoporosis.

Yes there are pt that develop endocrine issue due to medications that are used for treatment of other diseases...we are seeing issues of diabetes and hypophysitis with checkpoint inhibitors or thyroid issues with drugs like amiodarone that are treating life threatening arrhythmias and we work around it...the trade off of treating someone’s adrenal insufficiency with hydrocortisone is worth the increased life expectancy for someone with metastatic melanoma...or treating their diabetes if they are taking keytruda...

But in those cases, we can treat the adverse reactions to decrease the problems...but giving someone high doses of a medication to treat one issue,knowing we increase their chances of them having issues that could be life threatening? common sense tells me it’s not a good idea but I don’t have the data off the top of my head to back that up...and I’m on vacay at the moment so haven’t been checking in here as frequently

Thanks! I am getting the sense that from the endocrinology perspective, based on your all's goals, this approach rarely makes sense and is ill-advised. It also sounds like maybe a quantitative assessment of the relative risk is not easy to calculate or super well-established. I get not having the energy to dig up papers, so I suppose I will go back to trying to identify them myself. Any recommendations of particularly strong/non-crazy authors or groups working on this?

I frequently prescribe lithium and clozapine. These drugs definitely kill people or cause organ failure sometimes. Even very common stuff like risperidone definitely causes metabolic syndrome and progression to frank diabetes in some people and is associated with a significant increase in sudden cardiac death as I mentioned.

All those drugs, though, also come along with decreased all cause mortality. Real deal bipolar disorders shave around 10 years off life expectancy and have a ~15% suicide completion rate. So you can perhaps see why I am interested in getting numbers to get granular in helping patients make decisions about this!

 

[clausewitz2]

Let's make it more concrete. What are the glaring flaws you guys see from an endocrinology perspective in, for example, this paper:

https://www.sciencedirect.com/science/article/pii/S0165032714002067