Research about levothyroxine and cholesterol

[Mollyfan]

I have just seen this paper which confirms that hypothyroid patients “adequately” treated on T 4 alone have a higher cholesterol than euthyroid people and that T3 may be required to bring it down. This is certainly the case for me.

thyroid.org/patient-thyroid...

[helvella Administrator]

I do appreciate your use of quotation marks!

Patients with hypothyroidism adequately treated with levothyroxine have higher levels of cholesterol compared to healthy controls.

Which should really be rethought as "What does it mean to claim that patients with hypothyroidism are adequately treated?" In my view, it must require wellness and all biochemical markers to be restored. Otherwise it is self-evidently not adequate treatment!

Whether it is ever possible with T4-only is, indeed, a good question. But how can they, in one little article, both define the treatment as being adequate and also "suggests that L-T4 alone is not sufficient to normalize cholesterol levels"? Mutually contradictory.

[Mollyfan in reply to helvella]

I agree entirely!What is “adequate “ treatment and how does this relate to TSH, if at all?

Shouldn’t hypothyroid patients be entitled to be treated so that their cholesterol level ( and heart disease risk) is normalised?

I thought this paper might be something to wave under an unhelpful GP’s nose.

[tattybogle]

It's nice to see something discussing other measurable markers of thyroid function:-

"normalization of these thyroid hormone therapy markers...... cholesterol and creatine kinase levels, brain function and energy expenditure should also return to normal. "

There is also this one suggesting optimal TSH level on Levo rather than merely 'adequate' ie 'anywhere in range TSH' is needed to normalise cholesterol... healthunlocked.com/thyroidu....

You have to wonder how many of the 'adequately' treated patients in the data were actually 'optimal' on Levo , and how many of them still had TSH of 3 or 4.

[Nanaedake]

One thing to bear in mind is this study looks at patients going back to the 1970's. It's only since 2013 that it has been acknowledged that manufactured levothyroxine was poorly regulated with lack of bioavailability and bioequivalence. Also it has since been reclassified so that the correct dissolution tests must now be applied. Therefore, I might conclude that most patients prior to about 2015 were inadequately treated with thyroud hormone.

Since nobody could guarantee levothyroxine's efficacy was as stated on the packaging and with fluctuations between brands and batches that patients and doctors were unaware of except they felt unwell, it would have been impossible to determine cause of symptoms and administer the right amount of levothyroxine consistently.

So, I might conclude that these results are not surprising at all but not particularly useful either as this aspect of health now needs to be assessed in patients who are receiving levothyroxine since levothyroxine was reclassified.

[helvella Administrator in reply to Nanaedake]

Mind, a look at twentieth century recalls in the USA does illustrate the issues. Lots of levothyroxine products were subject to recalls. In the end, the FDA acted by demanding all levothyroxine products had to be approved as if new medicines. I think this was completed for extant products in 2002.

These USA issues were also exploited by Synthroid to promote the somewhat artificial branded vs. generic arguments.

Yes, Synthroid did tend to meet potency requirements - because they used overage. Where they intentionally made the tablets at, say, 110% of potency and just assumed that this would drop by the time patients took them. This wasn't always the case. It also meant that anyone switching to Synthroid was likely to get a small increment in their dose. I suspect that often made patients feel slightly better.

In order words, overage was in practice used as part of Synthroid marketing. (Now banned. In both USA and UK manufacturers must target 100% potency.)

[Nanaedake in reply to helvella]

I think the dissolution tests applied to synthroid were faulty as my understanding is that it wasn't universally accepted that the dissolution test was unsuitable and had to be revised until after the MHRA investigations in New Zealand and the UK, with ensuing report released in 2013. So, no guarantee that absorption or utilisation of the synthroid product was consistent from patient to patient or batch to batch or when switched to a different product despite overage.

[Mollyfan in reply to Nanaedake]

While it is clearly true that batches of levothyroxine varied in efficacy, I am not sure this is relevant. The researchers looked at the relationship between “adequate” control of TSH and cholesterol levels. If a batch was stronger or weaker than normal, the TSH would have decreased or increased respectively and the dose would have been decreased or increased accordingly.

[Nanaedake in reply to Mollyfan]

Yes, possibly but because it takes 6 to 8 weeks until bloods can be tested the variability of effective dose would mean a lot of adjustment and some unnecessary under and over dosing along the way. The blood test is only a capture of that time and not the rise or fall in between. So, I think it could contribute to higher cholesterol levels. From my point of view, the problem is that we can't be sure due to the levothyroxine quality issues.

[Mollyfan in reply to Nanaedake]

We can’t be sure about anything as adequate focussed research has not been done, but there is plenty of evidence that cholesterol rises in inadequately treated hypothyroidism. Surely variable efficacy would cause overdosing as well as under dosing so it would be inaccurate to suggest that the overall effect would be a raised cholesterol in what is a large group of patients.

[Nanaedake in reply to Mollyfan]

The research was suggesting the findings were based on patients who were adequately replaced. It's likely they weren't consistently adequately replaced and yes, that might potentially cause raised cholesterol. However, if patients were consistently adequately replaced it might not cause elevated cholesterol.

It's an interesting question isn't it?

In patients with autoimmune disease, inconsistent dosing is much more likely to result in under-replacement if the guide is TSH level or TSH and FT4 when dose adjustments are made due to the often found disconnect between FT4 and FT3 with FT3 much lower percentage wise within the lab range. So, I think it's pretty hard to conclude anything much from this except that historically patients on levothyroxine had raised cholesterol levels but it doesn't follow this is necessarily inevitable when thyroid hormone is consistently optimally replaced.

Thyroid cancer patients are more likely to suffer from over dosing with inconsistent variable potency of levothyroxine as it would only take a very small amount extra to tip them into overmedication if they are on TSH suppression therapy.

The real challenge is how to consistently maintain optimal thyroid hormone levels and avoid variability or interference.

[helvella Administrator]

Well, L-T4 definitely wouldn't "normalize" cholesterol levels in those with familial hypercholesterolemia!