Consider T4+t3 Combination Therapy
To validate the low tissue T3 hypothesis, more and better-designed RCTs should be done. The RCTs carried out so far did not provide conclusive answers, as most if not all studies could be criticized for the following reasons: heterogeneous patient population including hypothyroid patients due to Hashimotos disease or thyroidectomy/131I therapy inclusion of patients irrespective of persistent symptoms too small a sample size wide variation in T4+T3 dosages in combination treatment and different primary and secondary outcomes . To promote discussions about an optimal study design, the American, European and British thyroid associations have recently published a consensus document, which is very helpful . My own recommendations for a new RCT comparing T4 monotherapy versus T4+T3 combination therapy would be:
Epicrisis
Choosing Your Best Medication
Choosing your best medication also requires a little self-assessment.
What Happens If A Patient Adds Some T3 Medication
The same mechanism occurs when a little T3 is added alongside T4 medication. But the results can be even more pronounced.
When a thyroid patient begins to add T3 to T4 medication, the first thing that happens is that free T3 levels increase.
FT3 levels rise and the thyroid patient feels better! This is not a surprise, as T3 is the biologically active thyroid hormone. This improvement can last for 2 to maybe 7 days.
But the improvement is often not sustained. It is a top-up of T3 after all, so why shouldnt it last?
The reason it frequently fails to last is due to the mechanism that I have explained above.
The lowering of TSH that comes with the increase in FT3, lowers the conversion rate of FT4 to FT3 . Consequently, for those patients who rely on some T4 medication , adding T3 medication can create an initial great result, which is then followed after some time by lower conversion of T4 to T3. The circulating T4 thyroid hormone that you have just does not convert to as much T3 anymore. You have added extra T3, but you have lost some converted T3!
The net result is often a good improvement of symptoms followed by FT3 dropping to a level that is just as low as it was, to begin with.
Some of you reading this may have added T3 thyroid medication and felt that increase in FT3, but then after some days, they may then have found themselves back where they started in terms of symptoms.
This is a very frequent pattern.
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How Quickly Does T3 Work
It can take weeks to feel the effects of added T3, but some people feel them right away.
Thyroid patient Leah felt immediate effects: “Within 20 minutes of taking my first dose of generic Cytomel, I was like a wilted flower put in water. On T3 I have my life back. I can hold down a full-time job I have enough energy to keep up with my grandchildren.”
Whats The Best Thyroid Medication
One of the most common questions I hear from Hashimotos and hypothyroid patients is, Which thyroid medication is best?
The truth is theres no one right answer because each patient is unique and responds differently to different medications.
The key is to find the medication, or combination of medications, that works best for you and then work with your doctor to make adjustments based on your lab results and progress.
So to help you determine which option is the best for you, lets look at the three main types of thyroid medications and weigh their pros and cons.
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Burden Of Chronic Disease And Burden Of Having To Take Medication
The awareness of having a chronic disease and lifelong dependency on thyroid medication could make patients unhappy and less healthy . Patients with persistent symptoms despite a normal serum TSH level frequently feel that their normal TSH presents a barrier to further evaluation. GPs and nurses often have inadequate knowledge of medication interactions and LT4 pharmacokinetics information exchange is usually restricted by time and often centered on symptoms rather than patient education . Positive correlations were noticed between satisfaction and being well-informed about hypothyroidism, whereas negative correlations were observed between satisfaction and expectations for more support from ones GP . Improvement of the interactions between physicians and patients could reduce barriers to optimal thyroid replacement .
Natural Desiccated Thyroid Medications Like Armour
These medications, called NDT, come from the dried thyroid glands of pigs and are natural, as opposed to synthetic, and include Nature Throid, WP Thyroid, and Armour®.
They provide all four types of thyroid hormones, including T4 and T3, so they are the most similar to your bodys natural thyroid function.
Because of this, many patients feel the best and see the greatest improvement in symptoms and labwork when taking these types of thyroid medications.
Some conventional doctors are reluctant to prescribe NDT medications, claiming the levels of thyroid hormones in them is inconsistent. This was actually true several decades ago, but regulations were put in place in the 80s that made hormone levels just as precise in NDT as they are in synthetic drugs.
Meanwhile, some integrative practitioners claim that NDT medications can worsen Hashimotos because they contain thyroglobulin, which is one of the substances attacked by your immune system if you have Hashimotos.
Most practitioners agree that this is incredibly rare and that as long as youre carefully monitoring antibody levels, NDT medications are completely safe to try.
UPDATE: Recently more rumors about NDT medications have surfaced, so I went directly to the suppliers to investigate the claims. Heres what I found out.
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Getting Affordable T3 Drugs
Because levothyroxine is considered the standard treatment, T3 drugs are frequently not covered by health insurance. If youâre not careful, adding T3 or switching to NDT could involve hefty out-of-pocket costs.
To make it affordable to add T3 into your thyroid hormone replacement therapy, here are a few tips:
Check the GoodRx prices. GoodRx surveys local pharmacies for the best prices and includes discount coupons to save you money on your medications.
âCheck with Mark Cubanâs CostPlus Drugs, an online pharmacy. While they donât currently have NDT, they offer excellent liothyronine prices.
How Is The Dose Of Thyroid Hormone Chosen
When you are first started on thyroid hormone, the initial dose is carefully selected based on information such as your weight, age, and other medical conditions. The dose may need to be adjusted periodically by your physician to keep the thyroid levels normal. Your physician will make sure the thyroid hormone dose is correct by performing periodic physical examination and checking TSH levels.
There are several brand names of thyroid hormone available. Although these all contain the same levothyroxine , there are different inactive ingredients in each of the brands. In general, it is best for you to stay on the same brand, or the same manufacturer of a generic for consistency. If a change in brand or manufacturer is unavoidable, you should make your physician aware of the change, so that your thyroid hormone levels can be rechecked. If your pharmacy or insurance plan changes your thyroid hormone to a generic preparation, it is important for you to inform your physician.
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Advantages Of Compounded T4 And T3 Thyroid Medication
Perhaps the greatest benefit to compounded thyroid medications is that you have the option to provide the exact dose of T4 and T3 that you want for the patient while controlling the inactive binders/ingredients that come with it.
This means that you can provide your body with quantities and dosages which are not possible with standardized thyroid medications such as Synthroid/levothyroxine.
For instance:
Lets say that your doctor starts you on 50mcg of T4 in the form of Synthroid and 25mcg of T3 in the form of Cytomel.
Lets assume that you are doing well on this formulation but you are not at 100%.
After looking at your labs you see that your free T3 is lower than it should be but your TSH is lower than you want it as well.
Your doctor could then adjust your medication to include 40mcg of T4 and 28mcg of T3.
This allows for the potential to alter both T4 and T3 levels simultaneously based on your thyroid lab tests.
Do you see the power here?
This sort of dosing is not available with any other type of thyroid medication because they come in standardized doses.
Beyond this primary benefit I think there are also several other benefits to using compounded thyroid medications:
Armour Thyroid Dosage And Administration
The dosage of thyroid hormones is determined by the indication and must in every case be individualized according to patient response and laboratory findings.
Thyroid hormones are given orally. In acute, emergency conditions, injectable levothyroxine sodium may be given intravenously when oral administration is not feasible or desirable, as in the treatment of myxedema coma, or during total parenteral nutrition. Intramuscular administration is not advisable because of reported poor absorption.
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When To Use T3 Thyroid Medication
Determining if you would benefit from T3 thyroid hormone is not as difficult as you might think.
As a general rule of thumb:
The more medical conditions you have, the more excess body fat you have, the more medications you are on, the more inflammation in your body… the more likely you are to benefit from T3.
Why?
Because all of these conditions create an environment inside of your body that favors the production of reverse T3 over T3.
That means you are in a state of thyroid resistance.
In a nutshell, your body is basically blocking the action of thyroid hormone at the cellular level, this can occur even though you have “enough” thyroid hormone floating around in your bloodstream.
When it comes to thyroid hormone we really don’t care how much is floating around in your blood, we really only care if thyroid hormone is getting inside your cells and turning on your genes.
But we don’t have a great way to test for this, so instead, we use surrogate markers such as reverse T3 and sex hormone binding globulin.
Most patients who stand to benefit from using T3 thyroid hormone fall into one or more of the following categories:
- History of chronic pain/fibromyalgia
While this list isn’t exhaustive, it does include the majority of patients who might benefit from the addition of T3.
It’s also important to consider T3 therapy if you are having any issues or remaining symptomatic despite taking thyroid medication.
A Recently Identified Polymorphism In The Gene Coding For The Type Two Deiodinase The Enzyme Responsible For The Regulation Of T3 Availability To The Tissues Has Been Proposed In Order To Help Identifying Subgroups More Likely To Benefit From T4/t3 Combination Therapy Another Polymorphism Located In Oatp1c1 A Thyroid Hormone Transporter Expressed At The Blood
Famed Dutch Endocrinologist Wilmar Wiersinga says in his editorial that more trials are needed but that signs are pointing to a drug combination scenario for the relief of some people.
Dutch endocrinologist Wilmar Wiersinga wrote an accompanying editorial, titled Do we need still more trials on T4 and T3 combination therapy in hypothyroidism?
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Inflammation Due To Autoimmunity
A cross-sectional study among patients with autoimmune hypothyroidism observed that TPO-Ab levels are related to goiter symptoms, depressivity, and anxiety . A meta-analysis observed an association between autoimmune thyroiditis and depression or anxiety . LT4-treated patients with persistent symptoms despite a normal TSH and high TPO-Ab were randomized to receive total thyroidectomy or continuation of LT4 treatment QoL and fatigue improved after total thyroidectomy. After 1.5 years, median TPO-Ab values were reduced from 2,232 to 152 kU/L in the surgical group, and from 2,052 to 1,300 kU/L in the medical group . The autoimmune neuroinflammation hypothesis is the only cause of persistent symptoms shown in Table 5, for which there existed a complete overlap between respondents agreeing or not agreeing with this particular cause . Obviously, respondents felt quite uncertain about this cause. However, the hypothesis remains plausible, as strengthened by a recent systematic review .
Epicrisis
Persistent symptoms in LT4-treated patients despite a normal TSH can have several causes. Whereas the low tissue T3 hypothesis was dominant a decade ago, nowadays many other causes are thought to be likely involved including unrealistic patient expectations, comorbidities, and the SSRD hypothesis. The multifactorial nature of persistent symptoms has evolved against the background of hype surrounding T4+T3 combination treatment in many countries .
Information For The Patient
Patients on thyroid hormone preparations and parents of children on thyroid therapy should be informed that:
1. Replacement therapy is to be taken essentially for life, with the exception of cases of transient hypothyroidism, usually associated with thyroiditis, and in those patients receiving a therapeutic trial of the drug.
2. They should immediately report during the course of therapy any signs or symptoms of thyroid hormone toxicity, e.g., chest pain, increased pulse rate, palpitations, excessive sweating, heat intolerance, nervousness, or any other unusual event.
3. In case of concomitant diabetes mellitus, the daily dosage of antidiabetic medication may need readjustment as thyroid hormone replacement is achieved. If thyroid medication is stopped, a downward readjustment of the dosage of insulin or oral hypoglycemic agent may be necessary to avoid hypoglycemia. At all times, close monitoring of urinary glucose levels is mandatory in such patients.
4. In case of concomitant oral anticoagulant therapy, the prothrombin time should be measured frequently to determine if the dosage of oral anticoagulants is to be readjusted.
5. Partial loss of hair may be experienced by children in the first few months of thyroid therapy, but this is usually a transient phenomenon and later recovery is usually the rule.
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Ndt And T4 Combination
Seen less often is the prescribing of NDT and Levothyroxine together, however, this is the combination I am on at the time of updating this article.
My body responded to NDT alone well, for several years, until the birth of my first child in 2020, after which it would optimise my Free T3 levels, but leave Free T4 at the bottom of the range. If I were to keep increasing my NDT in this situation, I would end up very overmedicated, so my doctor offered a small amount of Levothyroxine alongside the NDT .
Although controversial, I have benefitted hugely from this combination as the Levothyroxine raised my Free T4 to optimal levels, alongside an optimal Free T3. It works in a similar way to the synthetic T3 + synthetic T4 combo.
Some online sources may claim that this combo drives up Reverse T3 levels or exacerbates adrenal dysfunction Ive experienced neither of these and have only felt well on this combination for the last two years. There is also a lack of hard evidence behind these claims, so do keep in mind that different people and different bodies can respond differently to different medication types. What is most important is that a responsible doctor is managing these medications and testing you often enough to keep dosage correct for your needs.
Treating Hypothyroidism With Replacement T4 And T3
Doctors treat the symptoms of hypothyroidism by prescribing oral thyroid hormone replacement therapy. Some treatments for an underactive thyroid involve prescribing T4 replacements like levothyroxine sodium . Other treatments involve a combination of T4 and T3 replacement therapy.
According to a study in the Journal of Clinical Endocrinology and Metabolism, there is a move towards using combined replacement of T4 and T3 therapies. Some doctors prefer this because the combined T4 and T3 thyroid treatments may have less impact on quality of life and treat hypothyroidism better.23
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What Is Compounded Thyroid Medication
All of these medications have potential advantages and disadvantages and should always be considered!
While they are all approved to treat hypothyroidism they differ in the exact amount of hormones that they provide your body when you ingest them.
The most common thyroid medications prescribed include those which contain the most abundant thyroid hormone in your body known as T4 or thyroxine.
These medications are incredibly stable and have a long half-life but they require activation by certain enzymes in your body.
Other medications contain the most powerful and active thyroid hormone known as T3 or triiodothyronine.
T3 is incredibly potent but suffers from a short half-life and it can pack quite a kick.
The medication that I want to focus on today is one option that doesnt get a lot of attention and its known as compounded T4 and T3 thyroid medication.
Its unique among all of the other thyroid medications in that it is created only at compounding pharmacies.
These pharmacies are specialty pharmacies that can formulate medications to fit your specific needs.
Instead of standardized ingredients and dosages, such as those found within levothyroxine and Synthroid, compounding pharmacies can alter the doses of each thyroid hormone component and add it to an array of binders and fillers to match what your body needs.
Unfortunately, youve probably never heard of compounding pharmacies because most conventional doctors dont really like these types of pharmacies.