This recent paper does begin to tackle the problems of therapy with T4 only. It is a start in that it does recognise patients who need combination therapy and that past trials were inadequate to study this. Plus the prospect of a more controlled T3 dosing regimen. It's behind a paywall. However I ask myself why NDT couldn't do the job just as well.
Hypothyroidism is a common endocrinopathy, and levothyroxine is frequently prescribed. Despite the basic tenets of initiating and adjusting levothyroxine being agreed on, there are many nuances and complexities to consistently maintaining euthyroidism. Understanding the impact of patient weight and residual thyroid function on initial levothyroxine dosage and consideration of age, comorbidities, thyrotropin goal, life stage, and quality of life as levothyroxine is adjusted can be challenging and continually evolving. Because levothyroxine is a lifelong medication, it is important to avoid risks from periods of overtreatment or undertreatment. For the subset of patients not restored to baseline health with levothyroxine, causes arising from all aspects of the patient’s life (coexistent medical conditions, stressors, lifestyle, psychosocial factors) should be broadly considered. If such factors do not appear to be contributing, and biochemical euthyroidism has been successfully maintained, there may be benefit to a trial of combination therapy with levothyroxine and liothyronine. This is not supported by the majority of randomized clinical trials, but may be supported by other studies providing lower-quality evidence and by animal studies. Given this discrepancy, it is important that any trial of combination therapy be continued only as long as a patient benefit is being enjoyed. Monitoring for adverse effects, particularly in older or frail individuals, is necessary and combination therapy should not be used during pregnancy. A sustained-release liothyronine preparation has completed phase 1 testing and may soon be available for better designed and powered studies assessing whether combination therapy provides superior therapy for hypothyroidism.
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diogenes
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Monitoring for adverse effects, particularly in older or frail individuals, is necessary and combination therapy should not be used during pregnancy.
Do I infer that there is less, or no, need to monitor for adverse effects of levothyroxine monotherapy?
Do they have any evidence that combination therapy should not be used during pregnancy? We are, supposedly, in the era of evidence-based medicine. Which is often interpreted as no evidence is treated as being at least of equal weight to evidence NOT to do something.
Seems far more likely that they are being super-cautious (likely with legal liability being foremost), which might, in the fulness of time, prove to be the opposite of what is best for mother and baby.
Given the number of people who are intolerant of Levothyroxine, a combination dose of Levo / Liothyronine is not necessarily an alternative. The usual reason for the unsuccessful use of Levothyroxine in either mono or dual therapy is problems with conversion.
That said, one can understand why NDT is becoming so popular where a combination therapy is required. In my case, it is not quite as simple as that. Although there is no significant issue for me with conversion, as is the case with Levothyroxine, the fixed ratio of the hormones doesn’t give me sufficient flexibility. An FT4 of above 14 on a range (12-22) causes me problems. These may or may not - depending on one’s Endocrinological catechism - be the result of rt3. Whatever. My body hates Levothyroxine which barely converts at all and hates only a little less the T4 in NDT.
It isn’t unusual for people to add some Levo to NDT to bring up an FT4 which seems insufficiency. I’ve seen less evidence of the addition of Liothyronine to increase FT3 without bumping up FT4 by increasing.
One of our very helpful members has helped me to work out a route to this point, which involves using NDT, reducing some of the FT4 and replacing it with Liothyronine.
Sorry if this sounds complicated. We know what we mean (we think 😉)
Quite agree. Use of whatever works is the only answer.
I do very much think that there are things about desiccated thyroid which make it work differently. However, there is nothing magical about the T4:T3 ratio which will be fine for some, not others.
We really do need to get to the bottom of why levothyroxine is such a problematical substance. I know we have many ideas, some of which might be classed as "pet theories", but we all need to get beyond that. We need very clear, provable ideas.
I sincerely hope you'll get some. We've submitted a paper heavy on maths I'm afraid which shows how the whole HPT system works. In the general math solutions are included tolerance to T4-only therapy, seasonable variation, and why and how this system can switch between robust defence of the status quo in one state (eg euthyroid) to change, but smoothly adapt to a new demand eg non thyroidal illness where there are large changes. Current classical models cannot encompass these widely differing demands -I hope that reviewers will understand its basic challenge to present simplistic thinking - but it might be a hard road ahead.
Thank you, diogenes, I know you are making leaps in our understanding.
What has really got me, in all my involvement in thyroid issues, has been the attitude. It often feels as if there is no-one in the endocrinology establishment who both appreciates the current issues and actually wants to understand. Little feeling that anyone wants to take on the questions even as an intellectual exercise. A crossword puzzle of hormones. This probably calumniates against some good people, but it is my emotional assessment.
I think it's a matter of earlier work by Larsen and colleagues that cemented the FT4-TSH relationship but ignored or were unaware of the possible "interference" in this nice relationship by FT3 and its effects. The tendency in thyroid matters has been a rationalisation, to simplify diagnosis ideally to TSH. Unfortunately for them, Nature isn't playing their game. The simplification hasn't simply been discredited, new findings place the individual at the centre and not the numbers.
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