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 include3:
- 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
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 T44. 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
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 disease10—alarmingly severe hypothyroidism can even produce symptoms similar to those of Alzheimer's disease as well11 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.
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 form15. 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 monograph16, 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 thyroid17 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.
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 body2 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 that24 which is why levothyroxine sodium is the most widely prescribed drug for hypothyroidism and the fourth most prescribed drug in the world.25
On the other hand, some people prefer taking both synthetic T3 and T426 while others who aren’t able to convert enough T4 to T3 in the body essentially require T3 in their medication which 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 mcg28. 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 hypothyroidism29. 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 Combination Therapy
Several studies have shown the possible superiority of combination therapy (Liothyronine sodium with levothyroxine sodium)3233 while others have found no difference34. This inconsistency in the medical literature, as well as the possible side effects of combination therapy like palpitations35 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% doesn’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-q24.338)—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 T340 (and having too much T4 without enough IDII can even make the problem worse—T4 that that doesn’t become T3 is more likely to become reverse T3 which decreases the thyroid’s function as a whole40). T3 is, in theory and in practice, tantamount to essential for these individuals.
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 extent41 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 you/your patient as potent a tool-kit 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 relief44. 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 monotherapy46) might not be those that ought be exclusively used in the future.
Parting Considerations: the Industry, Dosing, and Nuance
Non-compounded medication, referred to elsewhere in this article as commercially available drugs, possess many properties that Empower emulates—these products are approved by the FDA for a reason, and their rigid profiles are designed to allow for standardized treatment physicians across the world can easily apply.47
It is crucial to remember this: the purpose of custom combination therapy & personalized compounding solutions is not meant to replace and certainly not to declare superiority over the conventional treatments offered by the pharmaceutical industry. Compounded medication is meant to offer physicians and patients alike every possible choice in combatting disorders that are, by the very nature of physiology, unique to each person. In some people, traditional methods like levothyroxine sodium work just fine. In others the persistence of symptoms, even if they’re markedly improved from before treatment, implies that traditional methods leave something to be desired. With hypothyroidism, this is roughly 75% of the population45 —75% of people may stand to gain from pharmacological solutions that go beyond convention, that consider and combat all of the possible nuances in treatment the disease might present.
In the case of hypothyroidism, a frequently overlooked nuance that many physicians find provides a readily accessible improvement in treatment is considering whether instant or extended release works better for a patient. Most all commercially mass-produced thyroid drugs only offer one or the other and in almost every case an instant release preparation (see: package inserts for the mass-produced products for each of the 3 classes discussed in this article).
Empower offers physicians & patients a choice in the matter, especially in light of a substantial body of evidence that asserts extended-release versions of Thyroid USP, levothyroxine sodium, and liothyronine sodium can provide some people superior results and an improved quality of life.48 49
Empower has the ability to compound Thyroid USP, T3 (liothyronine) and/or T4 (levothyroxine) alone or in customized combinations. These are also available in Immediate Release and Sustained Release preparations. Please contact the experienced professionals at Empower Pharmacy, and we will help you get your body back up to speed!
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