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Elevated levels of circulating thyroid hormone do not cause the medical sequelae of hyperthyroidism

For so many years, endocrinologists and GPs have been running scared of adequate thyroid hormone dosing - citing all the nasty signs and symptoms of hyperthyroidism.

It seems to take psychiatrists, cardiologists, and others to seek out and research whether that really is the case in humans who simply take a high dose of thyroid hormones.

Don't miss that this is only a "literature review" - not new research.

Prog Neuropsychopharmacol Biol Psychiatry. 2016 Jun 11. pii: S0278-5846(16)30080-X. doi: 10.1016/j.pnpbp.2016.06.001. [Epub ahead of print]

Elevated levels of circulating thyroid hormone do not cause the medical sequelae of hyperthyroidism.

Kelly T1, Denmark L2, Lieberman DZ3.

Author information

1George Washington University, Department of Psychiatry and Behavioral Sciences, 2120 L St NW, Suite 600, Washington, DC 20037(1); The Depression & Bipolar Clinic of Colorado, 400 East Horsetooth Road, Suite 300, Fort Collins, Colorado 80525(2). Electronic address:

2The Depression & Bipolar Clinic of Colorado, 400 East Horsetooth Road, Suite 300, Fort Collins, Colorado 80525(2).

3George Washington University, Department of Psychiatry and Behavioral Sciences, 2120 L St NW, Suite 600, Washington, DC 20037(1).



Clinicians have been reluctant to use high dose thyroid (HDT) to treat affective disorders because high circulating levels of thyroid hormone have traditionally been equated with hyperthyroidism, and understood as the cause of the medical sequelae of hyperthyroidism, such as osteoporosis and cardiac abnormalities. This conclusion is not supported by (HDT) research.


A literature review of research related to the morbidity and mortality of HDT treatment was performed.


There exists a large body of research involving the use of HDT treatment to prevent the recurrence of differentiated thyroid cancer and to treat affective disorders. A review of this literature finds a lack of support for HDT as a cause of osteoporosis, nor is there support for an increase in morbidity or mortality associated with HDT. This finding contrasts with the well-established morbidity and mortality associated with Graves' disease, thyroiditis, and other endogenous forms of hyperthyroidism.


The lack of evidence that exogenous HDT causes osteoporosis, cardiac abnormalities or increases mortality compared with the significant morbidity and mortality of hyperthyroidism requires an alternative cause for the medical sequelae of hyperthyroidism. One possibility is an autoimmune mechanism.


High circulating levels of thyroid hormone is not the cause of the sequela of hyperthyroidism. The reluctance to using high dose thyroid is unwarranted.

Copyright © 2015. Published by Elsevier Inc.


bipolar; etiology; hyperthyroidism; iatrogenic; morbidity; sequelae

PMID: 27302764 [PubMed - as supplied by publisher]

See also:

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.

9 Replies

This is just what I needed - thank you for finding and posting.

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The real problem is based on the variable human response to thyroid failure, emanating from the particular patient's exact status when well. By that I mean the unique interplay between thyroid and tissues regarding the control of T4-T3 conversion (i.e. how much does the thyroid do itself versus the body's completion of the job). Some people (a 10-15% minority) will be so good at body conversion that the thyroid is a more minor T3 supplier and therefore T4 treatment will be very sensitive when the thyroid fails (they can be easily overdosed on T4 however mildly, owing to the crude incremental 25 ug increase in T4 therapy at present the norm. Most will be in the middle (OK with T4). Another 10-15% are poor body converters (T4 isn't enough by itself and T3 has to be added to make up for the lack of thyroid's T3 supply). I think that if there are any patients potentially in difficulties with T4 mono therapy, it includes the really good body converters. They have what is called a low therapeutic index - that is small changes in T4 dose can have major effects on health. It may be these that dominate whatever findings there have been on osteoporosis and AF because of how hard it will be to control their dosage and how easy it is for them to be mildly overdosed. This group also combines with the other group (10-15%) that are poor body converters who need T3 when the thyroid fails. Thus, studies that don't discriminate between the various groups will not really separate out the different responses and thus could lead everyone into a general though faulty conclusion simply because of a minority's sensitive response. Sorry for the scientific discourse but this is my position at the moment from the studies we've done so far.


Your contributions are very much appreciated.

From a personal point of view, I was on 100 micrograms of levothyroxine for quite a while then started to feel under-dosed. Trying 125 micrograms, I felt over-dosed. Alternating 100 and 125 felt not quite right. When I found, and tried, some 12 microgram tablets, and started 112 every day, I felt better. That is what I continue to take.

Would appear to suggest I could be a really good body converter?

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Lucky (or unlucky) you Helvella.

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After many years of wishing I was a " really good body converter " it is interesting to hear that they have as much trouble as the poor (but actually it makes sense.)

And of course it isn't just down to one's make-up but one's choice, opportunity and attitude to life.

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Yes indeed, thank you diogenes - most interesting.


I'm a very good body converter on NDT😂 My experiences on Levo dosing were exactly the same as yours Rob but I never found 112mcg Levo tablets to see if I felt OK on those I am not about to try now. Fascinating article, thanks for posting.

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I'm not clear from this is it just bone problems they knock on the head or is it also heart? That's what my endo goes on about re t3 only.

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Also many Thyroid patients have low stomach acid, or gluten intolerance or other poor nutrient absorption issues, often causing low vitamin D, which can then be contributory factor for osteomalacia or osteoporosis.

It would be easy to misattribute the osteomalacia or osteoporosis being due to too much/too little thyroid replacement rather than poor nutrient issues.


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