All thyroid hormone medications have the potential to be effective: L-T4 (Levothyroxine), L-T3 (Liothyronine), and natural desiccated thyroid (DTE / NDT).
However, each patient is unique in their response to these medications.
Optimizing a patient’s lifelong therapy involves finding the right thyroid hormone medication, or a combination of them, to relieve as many symptoms of hypothyroidism as possible without causing symptoms of hyperthyroidism.
Most patients are offered only one therapy, L-T4 monotherapy (Synthroid, Levothyroxine, Eltroxin, Euthyrox).
This therapy is apparently effective for many patients.
However, a significant minority of patients on L-T4 therapy do not achieve relief of hypothyroid symptoms. The percentage of symptomatic patients is difficult to estimate.
- According to one estimate, there are at least “10% of hypothyroid patients who continue to suffer from poor quality of life despite normal TSH concentrations under substitution therapy with levothyroxine (L–T4).” (Berberich et al, 2017).
- According to Bianco and colleagues, it’s approximately 15% of patients (Rush University, 2016).
But statistics on this are untrustworthy. Doctors tend to attribute patients’ symptoms to other health conditions when their TSH is normal.
Patients themselves also minimize their hypothyroid symptoms and consider them just part of normal life with all its stresses, or part of aging, or part of menopause. It’s likely L-T4 monotherapy may have improved hypothyroid symptoms considerably without resolving them, and patients are so thankful for the overall improvement that they minimize their ongoing struggles.
Thryoid researcher Antonio Bianco explains that the tell-tale symptoms and biomarkers of hypothyroidism often come along with using L-T4 alone in order to normalize the TSH:
“Doctors should be telling their patients, ‘I’m going to normalize your TSH, but you’re going to be at a higher risk for gaining weight, experiencing depression and fatigue. It is also more likely that your cholesterol will go up.’ That’s what we should be telling patients, based on our study.” (Rush University, 2016)
Why are so many patients required to stay on this therapy despite continued signs and symptoms of hypothyroidism?
1. The healthy HPT axis model
The L-T4 monotherapy mode works hand in hand with TSH testing, and both of these tools assume T3 levels are being taken care of. However, T3 is at the very core of hypothyroid status.
In the untreated population, the hypothalamus-pituitary-thyroid (HPT) axis is characterized by the direct inverse relationship between TSH and T4 hormone levels in serum.
But the most important thyroid hormone, T3, does not fit neatly into the HPT axis’s two-part mathematical model. TSH does not have a direct 2-way mathematical relationship to T3 levels, only to T4.
Yet sufficient T3 hormone is absolutely essential to prevent a hypothyroid state in organs, cells and tissues. Thyroid hormone receptors have 10 times the affinity for T3 hormone than they do for T4. And if T4 happens to enter the receptor, we have not yet witnessed it do anything there. T4 is simply unable to do what T3 does. See further discussion in “Rationale: Low T3 Syndrome, part 1 and part 2.”
2. Conversion of T4 to T3
The healthy thyroid gland secretes approximately 20% T3 and 80% T4 (Kopp, 2013), although in fact its secretion of T3 varies based on the degree to which living thyroid tissue is stimulated by TSH.
Yes, T4 is the more abundant product by far, but don’t let its bigger number trick you. T3 is the potent form of thyroid hormone. T4 is only useful to you if enough of it becomes T3.
If you do not have a healthy thyroid gland, and you are on L-T4 monotherapy, you will have to depend on “peripheral” T4-T3 conversion to make up for the loss of thyroidal secretion.
Medical school teaches that sufficient T3 hormone will be created in the body by peripheral conversion when TSH and T4 are “normalized.”
This model is based on the way the thyroid hormone metabolism works in an _untreated_ human being without any thyroid hormone metabolism dysfunctions.
With those assumptions in mind, doctors are told that Free T3 testing “is not indicated” in thyroid therapy.
But by avoiding the Free T3 test or not interpreting it in context, the entire medical system can avoid confronting data that could prove this T4-T3 conversion theory false for some treated patients.
It is already being proven false in research.
L-T4 monotherapy reduces conversion rate for the average patient. According to Peterson et al, 2016, these patients have on average “10% lower free T3:free T4, total T3:free T4, and total T3:total T4 ratios.”
And that’s just an average. It means that for some patients who are “poor converters” of T4, the ratio is likely to be lower.
Why are patients unique in their T4 conversion ability? It’s complicated. Each person converts T4 hormone at a different rate in blood and peripheral tissues. Some of our differences are due to genes. See discussion of genetic polymorphisms that slow down conversion in “REVIEW: Genes MCT10 and DIO2 and combination therapy ” and “REVIEW: DIO1 gene affects T3:T4 ratio “)
Unfortunately, raising the L-T4 dosage will not necessarily raise a patient’s Free T3 level. The rate of hormone conversion does not continually increase the more T4 you add. T4 overabundance actually slows down conversion rate.
In addition, raising L-T4 dose can paradoxically trigger active T3 depletion, which is more harmful than just slowing down conversion.
When a steady dose of T4 hormone is continually slightly above a patient’s current metabolic set-point for T4 (which could be anywhere in reference range), or when a patient’s chronic or critical illness lowers that T4 set-point, the body protects itself by consuming or inactivating the hormones. In this state, T4’s conversion to reverse T3 increases, and T3 is also converted to T2 before it can enter thyroid hormone receptors. (See “GRAPHIC and discussion: T3 Depletion“)
As this hormone depletion occurs, TSH will not rise as long as higher T4 levels are maintained by a daily dose. As long as T4 levels suppress TSH, it can’t perform its usual role of rising to encourage T4-T3 conversion.
Unfortunately, if T3 drops too low and the patient becomes critically ill, the loss of this essential hormone can endanger one’s life. (see Rationale: Low T3 Syndrome, part 1 )
In critical illness, the body needs to increase T3 hormone to regain health and raise metabolism during the recovery phase, but this T3 increase can only occur if the patient’s T4 medication permits TSH to rise, and if the higher TSH can stimulate enough healthy thyroid gland tissue to secrete T3. If your body can’t feed you enough T3 to keep you afloat while your body is actively destroying T3, you may be out of luck.
3. Fear of T3 hormone
It is a medical rumor that the use of T3 hormone in therapy is unsafe. However, it is one of the two hormones we all have flowing through our veins.
The fear arises from T3’s greater potency than L-T4 and the lack of medical training for practitioners.
Any T3-based medication, both synthetic L-T3 (liothyronine) and desiccated thyroid (DTE/NDT) which includes both T4 and T3, can certainly lead to a hypermetabolic rate when overdosed. T3 hormone can lead to these symptoms more quickly than L-T4 medications.
But L-T4 can also be overdosed and cause hyperthyroid symptoms.
Both hormones can suppress pituitary TSH without rendering the patient truly hyperthyroid in their thyroid hormone levels. See “Rationale: Low TSH vs. true hyperthyroidism.”
It is unclear how it could be unsafe to supplement T3 when serum T3 levels are low in reference range or below reference, and when the amount prescribed is highly unlikely to result in T3 excess.
The main caution is for severely low T3 patients; they need to start slow with small doses split into 2 times or more a day, giving the body enough time to get used to T3 dosing effects and overall dose increases until T3 levels are optimized.
Thyroid medication is one of the most commonly prescribed medications. It is taken daily for the rest of one’s life. Therefore, pharmaceutical profit is immense even when the price per pill is low. For manufacturers, their desire to keep their market-share motivates them to sell their product and keep their customers happy.
For provincial health care systems, every lab test costs, and every doctor’s visit costs. For doctors, time is money. Every appointment takes time. Dismissing patient symptoms or giving different drugs to treat them is easier than fixing the underlying thyroid hormone issues. Simplifying therapy is more attractive than optimizing it.
Because of doctors’ fear of hyperthyroidism and T3 overdose, they fear that any therapy containing T3 would be costly and time consuming to monitor.
Unfortunately, the money “saved” by dumbing down thyroid therapy and forcing all thyroid patients to live with a suboptimal T3 level may cost the health care system.
Consider that a patients on this therapy may require more medications to treat the disorders that accumulate over time due to their suboptimal T3 levels.
“LT4-treated individuals have higher BMIs despite reporting lower calorie intake corrected by body weight, report lower physical activity levels, and are more often taking statins, beta-blockers, and antidepressants.” (Pedersen et al, 2016)
Doctors do not enjoy continually hearing patients’ annoying and chronic health complaints. There is ultimately more satisfaction for the doctor in a healthy patient than in a normalized yet superficial TSH test result.
Time and money can be saved by thyroid education: both doctor and patient need to learn enough. The more they both know, the less time and effort they will spend as they try to optimize the hormone levels.
What can we do?
Don’t assume L-T4 monotherapy works well for everyone. There is great potential harm in withholding T3 hormone and limiting Free T3 levels.
In the symptomatic patient with a T3 level below the healthy average (and it’s likely anywhere below midpoint of the reference range is unhealthy for maintenance), the arguments for effectiveness and safety are on the side of giving a patient T3 hormone.
Thyroid therapy is lifelong. Let’s offer the full range of therapy options and optimize every thyroid patient’s T3 hormone levels rather than forcing symptomatic patients to continue suffering for the rest of their lives.
Other Sources cited:
- Kopp, P. (2013). Thyroid hormone synthesis. In L. E. Braverman & D. S. Cooper (Eds.), Werner & Ingbar’s the thyroid: a fundamental and clinical text (10th ed..). Philadelphia: Wolters Kluwer/Lippincott Williams & Wilkins Health.
Rush University Medical Center. (2016, October 12). Hypothyroidism symptoms linger despite medication use, normal blood tests. Retrieved July 26, 2018, from https://www.sciencedaily.com/releases/2016/10/161012132038.htm
4 thoughts on “Why T4 monotherapy has dominated”