Paradigm shifts in thyroid hormone replacement therapies for hypothyroidism - Nature Reviews Endocrinology

[Andyb1205]

Very well worth the read, I've uploaded it here. The science is catching up to the patients, though it may take a little more time for medical practice to then catch up to the science. Patients require individualized therapy to alleviate symptoms.

drive.google.com/file/d/13K...

Original link: nature.com/articles/nrendo....

From the abstract:

"Impaired psychological well-being, depression or anxiety are observed in 5–10% of hypothyroid patients receiving levothyroxine, despite normal TSH levels. Such complaints might hypothetically be related to increased free T4 and decreased free T3 serum concentrations, which result in the abnormally low free T4:free T3 ratios observed in 30% of patients on levothyroxine. Evidence is mounting that levothyroxine monotherapy cannot assure a euthyroid state in all tissues simultaneously, and that normal serum TSH levels in patients receiving levothyroxine reflect pituitary euthyroidism alone. Levothyroxine plus liothyronine combination therapy is gaining in popularity; although the evidence suggests it is generally not superior to levothyroxine monotherapy, in some of the 14 published trials this combination was definitely preferred by patients and associated with improved metabolic profiles. Disappointing results with combination therapy could be related to use of inappropriate levothyroxine and liothyronine doses, resulting in abnormal serum free T4:free T3 ratios. Alternatively, its potential benefit might be confined to patients with specific genetic polymorphisms in thyroid hormone transporters and deiodinases that affect the intracellular levels of T3 available for binding to T3 receptors. Levothyroxine monotherapy remains the standard treatment for hypothyroidism. However, in selected patients, new guidelines suggest that experimental combination therapy might be considered."

It concludes:

"Are we really on the brink of another paradigm shift in the treatment of hypothyroidism? Or are we “in search of the impossible dream”, as an editorialist put it, of a thyroid hormone replacement therapy that treats all symptoms in all hypothyroid patients?"

[Andyb1205]

Thought I’d share some more interesting finds to complement the article. I’ve posted the first one before.

Defending plasma T3 is a biological priority

onlinelibrary.wiley.com/doi...

Variation in the biochemical response to L-thyroxine therapy and relationship with peripheral thyroid hormone conversion efficiency

pdfs.semanticscholar.org/ed...

Thyroid hormone replacement – a counterblast to guidelines

tpauk.com/main/wp-content/u...

Recent Advances in Thyroid Hormone Regulation: Toward a New Paradigm for Optimal Diagnosis and Treatment

frontiersin.org/articles/10...

[Supernovae in reply to Andyb1205]

Hi Andyb1205, thank you v much for posting the links they are really interesting. Wish I had the sort in of GP that I could discuss the issues with, he thinks TSH is the be all and end all......

[Andyb1205 in reply to Supernovae]

Luckily my new GP recently did take the time to listen to and understand my concerns, giving me a lab requisition with TSH, Free T4 and Free T3, and wrote “Hyperthyroid” for diagnosis so the lab people skip the governmental protocol and order the tests anyways (saving me the $50 it costs to self pay instead). But the real test will be in the coming weeks, so far so good but I will need put a battle.

The first step for a doctor to help his patients is to attentively listen. There’s this great quote attributed to the world famous Canadian doctor Wilder Penfield, “If you listen to a patient carefully the patient will tell you the diagnosis and if you listen even more carefully they will tell you the most appropriate treatment.”

[Supernovae in reply to Andyb1205]

So pleased you’ve got a helpful GP, I’ve decided to make an appointment with one of the other GPs at the surgery.

Now I can view my results on line, I can see that my TSH jumped from 1.32 to 4.31 between July 2015 and February 2016 and GP told me my result was normal! It was 5.42 in February 2017 when he increased my levo, he just had me labelled tired all the time!

( btw Top of range 4.2 )

Good luck with next step Andy

[Andyb1205 in reply to Supernovae]

I wish I knew what my TSH was years before I had the first test done, would help explain things. But yes, I respect my GP for trying his best to help me. Unfortunately GPS are quite uneducated about hypothyroid symptoms, with normal antibodies, ultrasound and pituitary tests, I will need to convince him that it could be hypothalamic. From his view I can see how that can come across as crazy, that I am filling in the blanks as I go along, but he did agree that there is a visible disconnect between my TSH and my T4/T3 (below range TSH now while T4/T3 linger around third of range). Let’s see how this goes, I just need to survive until I see this second endo who is open minded and patient recommended. First endo told the GP I need to diet and exercise and discontinue Synthroid.

Anyways thanks and best of luck to you too! I hope everything works out.

[Rmichelle in reply to Andyb1205]

You have made a excellent point there-having your thyroid tested when you are fit and felt good, how easy it would be knowing what to aim for!! Instead of trying to work out where in the range we feel good and how we will get there!!i think thats a fab idea. 😊😊

[Supernovae in reply to Andyb1205]

Thank you and to you too

[greygoose]

Disappointing results with combination therapy could be related to use of inappropriate levothyroxine and liothyronine doses, resulting in abnormal serum free T4:free T3 ratios.

I wonder what, exactly, they mean by that. If they mean the ratios found in euthyroid people, then they're barking completely up the wrong tree. I don't think things will progress until they get ove the idea that levels and ratios that are perfect for euthyroid people, should also be perfect for hypos. They're not. Because we're different and have different needs.

[Andyb1205 in reply to greygoose]

He’s missing the forest for the trees I think but I see where he’s coming from. Rather than relevance given to the “ratio” it should be given to “inappropriate levothyroxine and liothtronine doses” for said individual. His view is stuck in such a conservative and formalistic mud, that one shoe fits all, when that is what’s at the root of this whole debacle in the first place!

[greygoose in reply to Andyb1205]

Agreed.

[helvella Administrator]

Such complaints might hypothetically be related to increased free T4 and decreased free T3 serum concentrations, which result in the abnormally low free T4:free T3 ratios observed in 30% of patients on levothyroxine.

Please Sir!!! Isn't the free T4:free T3 ratio HIGH if the person has increased free T4 and decreased free T3?

(Or am I due a detention for not reading it properly?)

[TaraJR]

From their conclusion: '' 'Are we in search of the impossible dream' as an editorialist put it, of a thyroid hormone replacement therapy that treats all symptoms in all hypothyroid patients?"

Surely they don't mean a one-size fits all therapy? The problem that's existed for many years is that they insist on one treatment for everyone. They give us no choice, no options. We are all different, and need different treatments from each other.

[Andyb1205 in reply to TaraJR]

Indeed. What they rather need to develop is a more efficient delivery system for T3, and a synthetic update to NDT. Individualize treatment accordingly. Advancements in genetic mapping could help pin point which treatment is best for each patient, until then, trial and error with thyroid function tests as a guide would suffice.

It just came to my attention, shocking and puzzling actually, the cost of Cytomel in the U.K. I just looked up how much a month’s supply in Canada would run and it converts to just £25! What the heck is going on over there?!

[TaraJR in reply to Andyb1205]

It's a scandal. I assume you're in Canada? We have a major campaign running to get T3 cost down, but also to educate doctors in the use of other treatments apart from just thyroxine T4. Because of the wicked cost, the CCGs who run local medical care in every area have told all doctors not to prescribe T3. They hide behind "it isn't proven clinically effective". It's a nightmare and there are many very sick people here because of it. All down to big Pharma greed, and dire NHS procurement policy.