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Home: Tired of being Tired, Depressed, Constipated,
Can't Sleep or Think?

Cancer, Depression, Hair Loss, Vertigo, & Infertility Correlate
with Low Thyroid Levels

TSH Levels Fluctuate and often
do not Reflect Thyroid Levels

Osteoporosis, Gum Disease &
Bad Teeth are not from Low TSH

High Blood Sugar & Insulin Resistance Correlate with High T3

Thyroid Blood Tests to Diagnose a
Thyroid or Hormone Imbalance


Thyroid Lab Results are Affected
by the Time of your Last Dose

Thyroid Reference Ranges are too Broad; What is Healthy / Optimal?

Thyroid Hormone Medications:
T4, T3, or Desiccated (T4 + T3)


Thyroid Hormone Requires
Iron, Cortisol, Selenium, Iodine


Hyperthyroid Symptoms (Anxiety, Tachycardia), Hypothyroid Labs

Adrenal Fatigue or Low Cortisol:  Hydrocortisone (HC) Side Effects

Reverse T3: Side Effects of T3-only
(or why you need T4 too)

Insomnia, Incontinence, &
Vaginal Dryness Resolve with BHRT

Low Testosterone in Aging Men:
TRT for Andropause

Saw Palmetto, Stinging Nettle, and OTC Men’s Supplements

Asthma, Eczema, Allergies, Hives, and Yellow #5 (Tartrazine)

Graves' Hyperthyroidism:
Antithyroid drugs + Levothyroxine

High Altitude Sickness: Headache, Insomnia, and Hypothyroid?

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Thyroid Hormone Medications: T4, T3, or Desiccated (T4 + T3)

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Three different types of thyroid medications are used to restore thyroid hormone levels in hypothyroid patients, and each has pros and cons. 

Levothyroxine or synthetic T4 is the Standard of Care that endocrinologists have been taught to prescribe.  Synthroid is the oldest brand name, and generics are also available for very little cost.  Tirosint is a fairly new brand of T4 in gel cap form, with no food colors in any dose.  The problem with taking only a T4 medication is that a normal thyroid secretes a little T3 in addition to T4. [1]  So to truly replicate a normal thyroid, one should supplement both T4 and T3. [2]  In fact, the presence of T3 itself helps T4 conversion to T3 during prolonged critical illness. [12]

Cytomel or liothyronine (synthetic T3) is available by prescription, but difficult to get prescribed.  Most doctors have been taught that T4 is all that is necessary, so that’s all most will prescribe. 

Natural desiccated thyroid (NDT) is available in the US as Armour Thyroid and Nature-throid, but has had an availability problem in the last couple of years.  Many patients also reported that a reformulation of Armour in 2009 made the medication ineffective for them.  NP Thyroid became available in Nov 2010, but patients have reported availability problems in 2013.  WP Thyroid became available in 2013.  Erfa Thyroid, which is most like Armour before it was reformulated, can be ordered from Canadian pharmacies, but ample lead time is required to get through customs, and it may not be reimbursed by insurance.  A doctor’s prescription is required to place an order.  Shipment time from Canada has varied from four days to five weeks for me.  The five-week delay did not appear to be a customs issue; it was likely a local problem because we have had other problems with other US packages that never arrived.

Which medication should one choose?  Well like most things medical, that depends.  There are some who are militant that desiccated thyroid is the only way to go.  But it is contraindicated in some.  A few people on Graves’ forums have reported that their TSI antibodies increased and their thyroid eye disease worsened after they started desiccated thyroid.  The theory is that their antibodies recognized the pork antigens (desiccated thyroid is made from pig thyroids)  and mounted an attack.  Returning to synthetic T4 and/or T3 has often resolved the problem.  That said, there are many with Graves’ who take desiccated thyroid successfully.  So there are really no firm guidelines.  If your antibodies (TPO, Tg, TRab) increased or decreased significantly after starting desiccated thyroid, please share your story on the blog post:   Desiccated Thyroid contains T4, T3, and rT3, but little T2 or T1

T4 medications like levothyroxine usually result in lab tests with a free and total T4 in the upper part of the range, but a free and total T3 in the lower half.  When they report lingering hypothyroid symptoms to their doctors, these patients are usually prescribed additional T4.  Not surprisingly, this can cause the T4 to go over range.  This does not match the lab result of a person with a healthy thyroid.  To simulate a healthy thyroid’s output, one would have to take both T4 and T3.  One study compared the total T3/T4 ratios of healthy people to the ratios of T4-medicated patients and found a lower ratio in the T4-medicated patients.  A very simple way to equalize the ratios would be to add some T3. [3]

Most people on the thyroid forums who have been on synthetic T4 and then switched to desiccated thyroid report feeling better, especially if they have no thyroid gland.  So it’s a popular medication, it’s just difficult to find a doctor to prescribe it.  Desiccated thyroid is made from whole pig thyroids and therefore contains all the components found in a thyroid gland:  T4, T3, reverse T3 (rT3), diiodotyrosine (DIT), monoiodotyrosine (MIT), thyroglobulin, thyroperoxidase enzyme (TPO), hydrogen peroxide (H2O2), iodide, tyrosyl residues, and calcitonin (a hormone involved in calcium and bone metabolism). [7]  Calcitonin is not a thyroid hormone, but another hormone produced by the parafollicular cells, which just happen to be located within the thyroid.  Prescription calcitonin is administered by nasal spray or injection, because it is not absorbed well orally, so its effect in desiccated thyroid may be minimal.  However, there is probably a synergy with all these additional components that make desiccated thyroid a more complete and effective replacement therapy for some than the synthetic replacements.   People on desiccated thyroid tend to have healthier bones, but that may be from the T3, not the calcitonin.  Studies show T3 is essential to bone health.

T2 and T1 are supposedly the special ingredients in desiccated thyroid, but thyroid physiology textbooks say that only T4, T3, MIT, and DIT are produced in the thyroid gland, not T2 and T1.  Only trace amounts of T2 have ever been measured in thyroglobulin in the thyroid [10], and T1 cannot be formed by the available iodotyrosine building blocks, MIT (1 iodine) and DIT (2 iodine).  1+1 = T2, 1+2 = T3, and 2+2 = T4.  When a pair of iodotyrosines (MIT and DIT) couple together, they form a thyroid hormone, also known as an iodothyronine.  Perhaps the confusion is because one of the precursors is called diiodotyrosine (DIT), while T2 is also known as diiodothyronine. The words are similar but they are two different things:  DIT is a precursor with only one tyrosine ring, while T2 has two tyrosine rings and has measurable effects as a thyroid hormone.  Diiodotyrosine (DIT), like T4 and T3, has been found in the thyroid and in serum. [8]

T2 and T1 are made from deiodination outside of the thyroid gland. [7]  Deiodination is the process where an enzyme strips off one iodine from T4, resulting in T3 (or rT3). The process of deiodination continues and another iodine is stripped off forming T2 (there are three types of T2), then T1 (there are two types of T1), and eventually T0, otherwise known as a non-iodinated thyronine. [9] 

T2 has been detected in both serum and thyroglobulin, but one study found the production rate of T2 was very close to the combined T3 + rT3 production rate.  In other words, the T2 came from deiodination, not the thyroid. [11]  Desiccated thyroid cannot therefore be considered a major source of T2, since T2 levels in the thyroid gland are negligible.  

Thyroid hormone production was found to be pH dependent in one laboratory experiment.  The higher the pH, the more hormone was formed.  The majority of the hormone produced was T4, followed by rT3, T3, and then negligible amounts of T2.   No T2 was produced if the pH was below 6, though the other hormones were still produced at a pH of 5.  Another study referenced in this report determined that thyroglobulin from actual thyroid glands contained approximately 90% T4, 7.4% T3, 2.2% rT3, and 0.4% T2. [10]

If rT3 is made in the thyroid, then it would also be a component of desiccated thyroid.  Anyone taking desiccated thyroid is ingesting some amount of rT3, which is a normal, benign  metabolite of thyroid conversion, as discussed in the rT3 section.  They should not be surprised if their rT3 levels rise as their desiccated thyroid dose rises.

Does T2 have any biological activity?  Studies show that it does.  In one study, rats were fed a high fat diet, and some rats were given T2 for 30 days, while the control rats were not.  The T2 group showed reduced fat accumulation, triglycerides, cholesterol, fat content of the liver, and body weight, when compared to the control rats fed the same high fat diet, who were not given T2. [5]   Perhaps people with impaired T4 to T3 conversion also have impaired conversion to T2 also, and the T3 and other thyroid components in desiccated thyroid somehow help conversion. T3 and rT3 are the precursors to T2, and desiccated thyroid provides both, so the essential raw material is more available.  Anecdotally, this may explain why some people are unable to lose weight while on T4, but then lose the weight when they switch to desiccated thyroid.  Interestingly, enzymes convert T2 from both T3 and rT3, but it is rapidly converted from rT3, and only slowly from T3. [6]

Many on desiccated thyroid have lab results that show a low in range Total and Free T4 when their Free T3 gets into the optimal range (upper half).  This is because desiccated thyroid (pig thyroid) is approximately 80% T4, and 20% T3, while a normal human’s thyroid output is closer to 94% T4 and 6% T3. [4]  The simple remedy for people who test low on T4 is to just add some synthetic T4 to their desiccated thyroid.  Studies show that both T4 and T3 need to be optimal for mental and physical well-being.  The brain and body are in two different compartments, and some functions prefer T4, others T3. [4]

Other people do not convert their T4 to T3 as readily, so their labs will look fine on desiccated thyroid, with both Total T4 and Free T3 in the optimal upper half of the range.   Really poor converters will show Total T4 in the upper half, but Free T3 in the lower half.  These people have underlying conversion problems that should be addressed.  Is ferritin and cortisol optimal?  Are there other drugs like beta blockers being taken that may interfere with conversion?  Is the person diabetic?  If all factors have been addressed, then the ideal dose might be desiccated thyroid + additional T3.  Desiccated thyroid could be used as the base, with additional T4 or T3 added as necessary to bring the person’s thyroid labs into the optimal range, or to a point where they feel best.  This is usually accomplished by trial and error.

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[reference links inactivated for search engines; copy and paste the url at the end of the reference into your browser if you want to view the reference]

1.  Robertas Bunevičius, Gintautas Kažanavičius, Rimas Žalinkevičius, and Arthur J. Prange, Jr..  Effects of Thyroxine as Compared with Thyroxine plus Triiodothyronine in Patients with Hypothyroidism.  N Engl J Med 1999; 340:424-429.  http://www.nejm.org/doi/full/10.1056/NEJM199902113400603

2.  HF Escobar-Morreale, FE del Rey, MJ Obregon and GM de Escobar.  Only the combined treatment with thyroxine and triiodothyronine ensures euthyroidism in all tissues of the thyroidectomized rat.  Endocrinology, Vol 137, 2490-2502, 1996.  http://endo.endojournals.org/cgi/content/abstract/137/6/2490

3.  A. Mortoglou, H. Candiloros.  The serum triiodothyronine to thyroxine (T3/T4) ratio in various thyroid disorders and after Levothyroxine replacement therapy.  Hormones 2004, 3(2):120-126. http://www.hormones.gr/preview.php?c_id=91

4.  Robertas Bunevičius, Arthur J. Prange.  Notes on the Importance of Triiodothyronine for Mental Function.  The thyroid and brain: Merck European Thyroid Symposium, Seville, 2002, May 30 – June 2.   http://tinyurl.com/65ov2b9

5.  Lanni A, Moreno M, Lombardi A, de Lange P, Silvestri E, Ragni M, Farina P, Chieffi-Baccari G, Fallahi P, Antonelli A, Goglia F.  3,5-diiodo-l-thyronine powerfully reduces adiposity in rats by increasing the burning of fats. FASEB J 19: 1552–1554, 2005.  http://www.fasebj.org/content/early/2005/08/27/fj.05-3977fje.full.pdf

6.  Höffken B, Ködding R, Köhrle J, Hesch RD.  Conversion of T3 and rT3 to 3,3'-T2: pH dependency. Clin Chim Acta. 1978 Nov 15;90(1):45-51. http://www.ncbi.nlm.nih.gov/pubmed/31249

7.  Françoise Miot, Corinne Dupuy, Jacques Dumont, Bernard Rousset.  Thyroid Hormone Synthesis and Secretion. Thyroid Disease Manager. July 2010.  
http://www.thyroidmanager.org/chapter/thyroid-hormone-synthesis-and-secretion/ 

8.  Benker G, Splittstösser C, Meinhold H, Olbricht T, Reinwein D.  Effects of small doses of bovine TSH on serum levels of free and total thyroid hormones, their degradation products, and diiodotyrosine.  Acta Endocrinol (Copenh). 1985 Feb;108(2):211-6.  http://www.ncbi.nlm.nih.gov/pubmed/3969815

9.  A. J. Hulbert.  Thyroid hormones and their effects: a new perspective.  Biological Review, 75, 2000, 519-631.  http://tinyurl.com/cj37mkn

10.  Jan J M de Vijlder and Marcel T den Hartog.  Anionic iodotyrosine residues are required for iodothyronine synthesis.  European Journal of Endocrinology (1998) 138 227–231.  http://www.eje-online.org/content/138/2/227.full.pdf

11.  Laurence A. Gavin, Margaret E. Hammond, James N. Castle and Ralph R. Cavalieri.  3,3′-Diiodothyronine Production, a Major Pathway of Peripheral Iodothyronine Metabolism in Man.  J Clin Invest. 1978;61(5):1276–1285.  Volume 61, Issue 5 (May 1978).  http://www.jci.org/articles/view/109044

12.  Debaveye Y, Ellger B, Mebis L, Darras VM, Van den Berghe G.  Regulation of tissue iodothyronine deiodinase activity in a model of prolonged critical illness. Thyroid. 2008 May;18(5):551-60.  http://www.ncbi.nlm.nih.gov/pubmed/18466079

This website is for educational and informational purposes only and should not be taken as medical advice.  It is not exhaustive and cannot possibly cover all conditions.  It is your responsibility to consult a doctor for any diagnosis, treatment, and medication or supplement changes.  Any information followed without his/her advice is done at your own risk.  I am not a doctor, but a hypothyroid patient who had radioactive iodine treatment for Graves' hyperthyroidism who enjoys medical research.
Copyright © 2011-2014 by Barbara Lougheed.  All rights reserved.
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