Hypothyroidism General Information
Hypothyroidism is a state in which the thyroid gland does not produce enough of the two thyroid hormones. Although the people with the highest risk are women over 60,1 it can occur in people of all ages. Damage to the thyroid gland as a result from viral infections, drugs such as lithium, or radiation therapy for cancer, genetic predisposition, or an idiopathic source can all result in hypothyroidism.2 Symptoms of hypothyroidism may include:3
- Unexplained weight gain, puffy face, dry skin
- Elevated blood cholesterol level, slowed heart rate
- Pain, stiffness or swelling in your joints, muscle aches, fatigue
- Heavier than normal or irregular menstrual periods
- Thinning hair, hoarseness, constipation
- Depression, Impaired memory
The Two Major Forms of Thyroid Hormones
Thyroid hormone exists in two major forms: the prohormone (precursor) thyroxine (T4), an inactive form with a 4th iodine that is produced exclusively by the thyroid gland, and triiodothyronine (T3), the active form of thyroid hormone created by removing a specific iodine atom from T4.4 About 20 percent of T3 is produced by the thyroid gland, with the remaining majority of T4 produced in various tissues of the body when and where more T3 is needed.5
How Thyroid Hormone T3 Effects the Body
The active form of thyroid hormone (T3) helps control heart rate and blood pressure and therefore a thyroid hormone imbalance has a profound effect on cardiovascular fitness.67 When T3 levels drop, the liver no longer functions properly and produces excess cholesterol, fatty acids, and triglycerides, which increase the risk of heart disease.8 Additionally, hypothyroidism is the second leading cause of high cholesterol, after diet.9 High cholesterol may also increase the risk of Alzheimer's disease.10 Alarmingly severe hypothyroidism can even produce symptoms similar to those of Alzheimer's disease as well,11 and T3 is further important in the production of neurotransmitters and myelin, thusly it is critical to the health of the mind as a whole.12 With such a far-reaching sphere of influence, it isn’t surprising to see that thyroid function is of great concern to medical professionals and when a person begins showcasing symptoms of hypothyroidism, doctors immediately turn to pharmaceutical solutions.
Thyroid Medication Options
The four classes of thyroid medication offered by Empower encompass the complete spectrum of treatment options available and are designed to meet each patient’s specific needs: Thyroid USP, isolated from natural porcine thyroid,13 offers patients both T4 and T3; levothyroxine sodium, the most commonly prescribed thyroid medication globally,14 is synthetic T4 in a stable sodium salt form; liothyronine, and custom combinations for combination therapy sodium, synthetic T3 in the same stable sodium salt form.15 Additionally, Empower is able to help physicians develop personalized formulations for combination therapy.
Currently, Desiccated Natural Thyroid - Thyroid USP - is available in all strengths only through compounding pharmacies. The specifications for Thyroid USP powder require that each grain contains 34.2-41.8 mcg levothyroxine (T4) and 8.1-9.9 mcg liothyronine (T3) in order to produce a T4:T3 ratio of 4.22:1 to meet the stringent standards of the U.S. Pharmacopeia monograph,16 with a permissible variance of ± 10%.16 Armour Thyroid, WesThroid, and Nature-Throid, some of the most widely used brand-name versions of desiccated thyroid, also adhere to these guidelines. However, the different brands of Thyroid USP contain other ingredients than just desiccated thyroid:17 18 19 fillers, dyes, binders, stabilizers, excipients, many of these compounds can be a concern for patients with allergies. These additional compounds carry the potential to affect the properties of the drug itself as the public outcry over the purported 2009 reformulation of Armour Thyroid so clearly demonstrates.20 This is why Empower Pharmacy’s formulation is a gelatin capsule containing desiccated thyroid, a natural cellulose filler and nothing more.
Compounding Process of Thyroid USP
Through a very meticulous process, compounding specialists at Empower Pharmacy use this raw thyroid powder to compound Thyroid USP. If you are already on Thyroid USP but have a unique dose, Empower's custom preparations could mean it's no longer necessary to split your Thyroid USP tablets—we create customized doses not commercially available. In addition, if you have side effects due to the inactive ingredients of the Armour Thyroid, WesThroid, or Nature-Throid brands, we can compound the strength you need with minimal fillers. By prescription, we can compound Thyroid USP in the doses that your patients need, and can omit problem-causing fillers and excipients that are found in the commercial product but may not be tolerated by all patients.
Levothyroxine Sodium (T4)
However, due to the difference between pig and human T4 to T3 ratios (4.22:1 in pigs and 14~20:1 in humans)21 as well as considerable variation in levothyroxine (T4) and liothyronine (T3) [levels], porcine thyroid hormone has been largely replaced in clinical pharmacological therapeutics by synthetic levothyroxine (T4), which has a more reliable hormonal content.22
Levothyroxine Sodium (T4), the most widely used form of treatment for hypothyroidism, helps elevate T3 levels by introducing additional amounts of T4 into the body so that more T3 can be created in the tissues of the body that need it.23 The rationale behind using levothyroxine sodium (T4) alone (monotherapy), is that the thyroid only makes 20% of the body’s T3—the other 80% is made from T4 elsewhere in the tissues of the body.2 So by bringing up a patient’s T4, T3 ought be more readily made throughout the body. Levothyroxine sodium relies on the conversion of T4 to T3 to combat the deficiency of both thyroid hormones throughout the body: only by successfully and sufficiently converting T4 to T3 does the body reap the full benefits of levothyroxine sodium. Fortunately, a demanding majority of the hypothyroidic population is able to do just that,24 which is why levothyroxine sodium is the most widely prescribed drug for hypothyroidism and one of the most prescribed drugs in the world.25
Liothyronine Sodium (T3)
On the other hand, some people prefer taking both synthetic T3 and T4,26 while others who aren’t able to convert enough T4 to T3 in the body, essentially require T3 in their medication. This is why Empower provides physicians with all the components along the continuum of thyroid treatment options: desiccated thyroid (T4 & T3), levothyroxine sodium (T4), and lastly liothyronine sodium (T3); a T3 deficiency cannot be fully treated if the rate at which T4 is converted to T3 is hindered.
Synthetic T3 (liothyronine) is commercially available only as an immediate-acting preparation, which may cause undesirable side effects including heart palpitations27 in the recommended dose of 5-50 mcg.28 This is why some practitioners choose to use lower doses of T3 or provide T3 as a sustained release preparation, both of which are available from our compounding pharmacy.
While liothyronine sodium is not typically employed by itself to combat hypothyroidism,29 some people still find it works best for them. Interestingly, the most prominent use of T3 on its own (monotherapy) is in combating certain forms of depression due to the effect T3 indirectly exerts on serotonin levels.30 Liothyronine is not, though, typically employed by itself to combat hypothyroidism.29 However, there are proponents in the medical community who believe that T3 monotherapy can provide certain patients relief from their symptoms they were unable to attain with Thyroid USP or levothyroxine previously.31 On the whole, liothyronine sodium is far more frequently utilized in combination with levothyroxine sodium in what’s known as “combination therapy”.
The Case for T3/T4 Combination Therapy
Several studies have shown the possible superiority of combination therapy (Liothyronine sodium with levothyroxine sodium),3233 while others have found no difference.34 This inconsistency in the medical literature, as well as the possible side effects of combination therapy like palpitations,35 have led some experts to conclude that there is no benefit to using T3 for treating hypothyroidism.36
Yet where these studies don’t offer an indisputable rationale either for or against T3/T4 combination therapy, the very genes of 15% of the hyporthyroidic population provide a compelling justification: while 85% of the population is able to successfully increase T4 and T3 levels when treated with levothyroxine sodium (T4) alone, the other 15% don’t see enough of an increase in their levels of T3 even though T4 levels are increased.37 This happens because that 15% has a different form (polymorphism) of the gene DIO2 (14q24.2-q24.3).38 This gene is not expressed as much or as easily as it is in the rest of the population and as a result, the enzyme it creates, type 2 deiodinase (IDII), one of the two enzymes that convert T4 into T3,39 is not as prevalent making a person in this 15% of the population less able to turn T4, even when supplemented, into a sufficient supply of T3 throughout the body. Without enough functioning IDII, more T4 will become rT3 than is normal, which can further decrease thyroid function.
The gene DIO2 is a fantastic case-study in why treating all cases of hypothyroidism with the same conventional methodology might not be the most prudent approach, nor might it yield the best results. These are two populations that react very differently to typical levothyroxine sodium treatment: while one group achieves the desired T3 levels, the other does not. For these individuals, levothyroxine sodium (T4) alone is incapable of fully remedying the symptoms of hypothyroidism: these people cannot convert their new, large stores of T4 into T3.40 Having too much T4 without enough IDII can even make the problem worse because T4 that that doesn’t become T3 is more likely to become reverse T3 which decreases the thyroid’s function as a whole.40 T3 is, in theory and in practice, tantamount to essential for these individuals.
Empower Offers Custom Thyroid Solutions
As is the usual in medicine, the answer to “what thyroid medication is best for me?” is not be a simple one, nor should it be: Thyroid USP, Levothyroxine, Liothyronine, and combinations in concert all carry a unique profile of advantages, disadvantages, and nuance. 75% of all medicated hypothyroidics still experience at least one symptom to varying extent,41 and it is absolutely imperative that healthcare providers have every resource and every tool at their disposal if a patient is to achieve an optimal quality of life.
This is why Empower offers as potent a tool-kit as possible: Thyroid USP, Levothyroxine, Liothyronine - with complete control over dose composition and strength, binder, filler, and excipient alternatives, and the ability to decide whether or not to utilize instant or extended release.
While it has been demonstrated that some people can experience unpleasant or sub-optimal results from combination therapy,42 there are also those who experience both qualitative43 and quantitative benefits/symptom relief.44 Everyone’s solution is unique, and considering that roughly 75% of all medicated hypothyroidics still experience at least one symptom of their disease to an extent,45 it follows that the treatment practices proclaimed as the universal gold standard in the past (levothyroxine sodium monotherapy)46 might not be those that ought be exclusively used in the future.
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- 1. Garber J, et al. “Clinical Practice Guidelines for Hypothyroidism in Adults”. Thyroid. 2012;22(12):1200-35.
- 2. a. b. Longo D, et al. “341: Disorders of the Thyroid Gland”. Harrison’s Principles of Internal Medicine. (18th ed.). New York: McGraw-Hill.
- 3. DeRuiter J. “Thyroid Hormone: Thyroid Pathology.” PYPP 5260-Endocrine Module. Auburn University. 2002.
- 4. “Hypothyroidism.” Hypothyroidism Patient Brochure. American Thyroid Association. 2014.
- 5. Zhang J, Lazar M. “The Mechanism of action of Thyroid Hormones.” Annual Review of Physiology.” 2000;62:439-66.
- 6. Kahaly G, Dilmann W. “Thyroid Hormone Action in the Heart.” Endocrine Reviews. Jul 1 2013;26(5):704-728.
- 7. Fazio S et al. “Effects of Thyroid Hormone on the Cardiovascular System.” Recent Progress in Hormone Research. 2004;59:31-50.
- 8. Shin D, Osborne TF. “Thyroid Hormone Regulation and Cholesterol Metabolism Are Connected through Sterol Regulatory Element-binding Protein-2 (SREBP-2).” The Journal of Biological Chemistry. 2003;278:1-5.
- 9. Lowrance J. Cardiac Effects of Hypothyroidism and Hyperthyroidism: Heart Problems caused by Thyroid Disease. Self-published eBook. 2014.
- 10. Luigi P, et al. “Alzheimer’s disease: the cholesterol connection”. Neuroscience. Nature Publishing Group. 2003 Apr;6(4):345-51.
- 11. Tan Z, Vasan R. “Thyroid Function and Alzheimer’s Disease.” Journal of Alzheimer’s Disease. 2009;16:503-507.
- 12. “Kapaki E et al. “Thyroid function in patients with Alzheimer’s disease treated with cholinesterase inhibitors.” ACTA Neurobiologiae Experimentalis. 2003;63:389-392.
- 13. Armour Thyroid package insert. St. Louis, MO: Forest Pharmaceuticals Inc.; 2012 Aug.
- 14. Professional Guide to Drugs-A Reference for Doctors, Nurses, Dentists, Pharmacists-Anyone Who Prescribes, Administers, or Takes Medicines. Cal State Long Beach Library: Intermed Communications Books. 1982. P. 592.
- 15. ”Liothyronine-Description.” Clinical Pharmacology. 2013 Aug 23. Web.
- 16. a. b. Us Pharmacopeia Natural Formulary USP 37 N32 2014 Volume 3 May 1, 2014. The United States Pharmacopeial Convention. 2014.
- 17. Women’s International Pharmacy. ”Thyroid Hormone Therapy Options”. 2014. Web.
- 18. The United Pharmacopeial convention, USP 36 Official Monographs, Thyroid p 5383. December, 2013.
- 19. Armour Thyroid (thyroid tablets) package insert. St. Louis, MO: Forest Pharmaceuticals, Inc.; 2011 Jan.
- 20. Shomon M. “Armour Thyroid’s Spring 2009 Reformulation Causing Problems”. About.Thyroid. About.com. 2014 Aug 18. Web.
- 21. Wiersinga W. “do we need still more trials on T4 and T3 combination therapy in hypothyroidism?” European Journal of Endocrinology. 2009;161(6):955-9.
- 22. “Description-Desiccated Thyroid. Clinical Pharmacology Database. Elsevier. Aug 1 2013.
- 23. Zhang J, Lazar M. “The Mechanism of action of Thyroid Hormones.” Annual Review of Physiology.” 2000;62:439-66.
- 24. Friedman, Theodore, MD Ph.D. “The 15% Rule of Who Should Get T4/T3 Combination.” www.goodhormonehealth.com Good Hormone Health. 2001.
- 25. ”The Top 10 Most Prescribed Drugs”. WebMD. WebMD, LLC.
- 26. Escobar-Morreale HF, Botella-Carretero JI, Escobar del Rey F, Morreale de Escobar G. “Review: Treatment of hypothyroidism with combinations of levothyroxine plus liothyronine. Journal of Clinical Endocrinology and Metabolism. 2005;90:4946-54.
- 27. ”Liothyronine USP Safety Data Sheet”. Reference Standards. US Pharmacopeia. 2009 Apr 10;3:5659-65. Revised: 2012 Nov 26.
- 28. ”Liothyronine Sodium-liothyronine sodium tablet. Carilion Materials Management. 2014 May.
- 29. a. b. Vanderpump M, et al. “Consensus statement for good practice and audit measures in the management of hypothyroidism and hyperthyroidism.” British Medical Journal. 1996 Aug 31;313:539-44.
- 30. Weissel M. “Administration of thyroid hormones in therapy of psychiatric illnesses.” Acta Medical Austriaca. 1999;26(4):129-31.
- 31. Robinson P. Recovering With T3: My Journey from Hypothyroidism to Good Health Using the T3 Thyroid Hormone. Elepahant in the Room Books. 30 Nov 2011.
- 32. Nygaard B et al. “Effect of combination therapy with thyroxine (T4) and 3,5,3’-triiodothyronine versus T4 monotherapy in patients with hypothyroidism, a double-blind, randomized cross-over study.” European Journal of Endocrinology. 2009;161(6):895-902.
- 33. Bunevicius R, Kazanavicius G, Zalankevicius R, Prange AJ Jr. “Effects of thyroxine as compared with thyroxine plus triiodothyronine in patients with hypothyroidism. New England Journal of Medicine. 1999;340: 424-9.
- 34. Clyde P, et al. “Combined Levothyroxine Plus Liothyronine Compared with Levothyroxine Alone in Primary Hypothyroidism: A Randomized Controlled Trial. ” Journal of the American Medical Association. 2003;290:2952-8
- 35. ”Liothyronine USP Safety Data Sheet”. Reference Standards. US Pharmacopeia. 2009 Apr 10;3:5659-65. Revised: 2012 Nov 26.
- 36. British Thyroid Association Executive Committee. “Armour Thyroid (USP) and combined thyroxine/tri-iodothyronine as Thyroid Hormone Replacement.” A Statement from the British Thyroid Association Executive Committee, November 2007. Nov 2007.
- 37. Friedman, Theodore, MD Ph.D. “The 15% Rule of Who Should Get T4/T3 Combination.” www.goodhormonehealth.com. Good Hormone Health. 2001.
- 38. ”DIO2.” Hugo Gene Nomenclature Committee. EMBL-EBI.
- 39. “DIO2 deiodinase, iodothyronine, type II [Homo sapiens (human)].” Genes & Gene Expression Database, National Center for Biotechnology Information. U.S. National Library of Medicine. Bethesda, MD.
- 40. a. b. Gavin L, Castle J, McMahon F, Martin P, Hammond M, Cavalieri R. “Extrathyroidal Conversion of Thyroxine to 3, 3’, 5’-Triiodothyronine (Reverse-T3) and to 3, 5, 3’-Triiodotyronine. Journal of clinical endocrinology and Metabolism. 1977;44(4):733-42.
- 41. Milner M. “Hypothyroidism: Optimizing medication with Slow-Release Compounded thyroid Replacement.” International Journal of Pharmaceutical Compounding. 2005;9(4):268-273.
- 42. ”Liothyronine USP Safety Data Sheet”. Reference Standards. US Pharmacopeia. 2009 Apr 10;3:5659-65. Revised: 2012 Nov 26.
- 43. Robinson P. Recovering With T3: My Journey from Hypothyroidism to Good Health Using the T3 Thyroid Hormone. Elephant in the Room Books. 30 Nov 2011.
- 44. Myhill S. “Thyroid-the correct prescribing of thyroid hormones.” Dorctor Myhill: Empowering you to Recover your Health. Sarah Myhill Limited. Upper Weston, Llangunllo, Knighton-Powys, Wales, United Kingdom.
- 45. Milner M. “Hypothyroidism: Optimizing medication with Slow-Release Compounded thyroid Replacement.” International Journal of Pharmaceutical Compounding. 2005;9(4):268-273.
- 46. .British Thyroid Association Executive Committee. “Armour Thyroid (USP) and combined thyroxine/tri-iodothyronine as Thyroid Hormone Replacement.” A Statement from the British Thyroid Association Executive Committee, November 2007. Nov 2007.