Have just completed a first draft discussing the NICE-recommended approach of dosing by weight.
This is entirely my personal opinion. Not official in any sense. Not Thyroid UK.
As such, it is certainly open to discussion and disagreement. Even spelling and grammar! 
helvella – Dosing By Formula
Excellent post. Can you send it to 'the committee'? Or publish it in bmj?
One of the papers associated our group discusses this very thing. Two alternatives are discussed and the use of TSH as a titration for dose questioned.
Do Thyroid-Stimulating Hormone, Body Weight, or Body Mass Index Serve as Adequate Markers to Guide Levothyroxine Dose Titration?
October 2013Journal of the American College of Surgeons 217(4):752-3
DOI: 10.1016/j.jamcollsurg.2013.06.008
Johannes W. DietrichJ, Melvin Khee Shing Leow, Simon L. Goede, Rudolf Hoermann
Is there any way to read this it seems to be behind a paywall with no abstract? Ta
I've extracted the body of the paper as underneath:
Ojomo and coauthors published a retrospective evaluation of patients post-thyroidectomy, concluding that maintenance levothyroxine (L-T4) doses are best predicted by body mass index (BMI) rather than by the traditional practice of measuring body weight.
Others concomitantly used an even larger cohort, showing
instead that L-T4 doses were better estimated by body
weight than by BMI.
Why do 2 trials addressing the same issue in similar
settings arrive at opposite conclusions? One of the reasons
may emanate from the statistical methodologies used.
Multivariate logistic regression may result in fallacious
rejection of explanatory variables in situations of multi-
collinearity, when measurements of body weight and
BMI were both included in one of the trials.
Both articles demonstrated that a daily L-T4 substitution dose between 1.5 and 1.6 mg/kg was required to achieve euthyroidism, which does not depart significantly
from traditional dosing recommendations. However, the
same outcome was attainable by BMI-based dosing
between 25 and 34 kg/m
2
The weight-based formula is inaccurate at the extremes of body weight unlike BMI; the former does not account as well for the volume of L-T4 distribution as the latter.
Notably, both trials relied purely on a thyroid-
stimulating hormone (TSH)-centric approach to estimate
adequacy of substitution dose. It was recently demonstrated that TSH alone might be an insufficient yardstick
to define the degree of euthyroidism because hormone
concentrations in the hypothalamic-pituitary (HP) unit
may equilibrate with circulating iodothyronines at
different rates compared with peripheral tissues.
Moreover, TSH secretion is influenced not only by T4 levels,
but also by structural parameters of the feedback loop,
neuromodulators/cytokines, and hysteresis.
A disconcerting weakness in both articles is that individ
uals were collectively compared using inferential statistical
techniques without regarding underlying physiologic prin
ciples. A composite of euthyroid TSH values within the
population reference range from diverse people, when
decoupled from corresponding free T4 (FT4), yields
a noisy scatter of “pseudo-random” data points concealing
an ordered structure, which the statistics fail to unravel.
Owing to wide variation, the proposed formulas, although
showing significant association at the population level, are
not very useful according to our data as instruments
for fine-tuning of dose-adequacy in an individual
It is crucial to appreciate that individuals behave
fundamentally as stochastically independent entities,
each controlled by their own characteristic HP axis. This
should be best analyzed using groups of individualized
TSH-FT4 curves. We believe that systems theory repre-
sents the appropriate approach to study such TSH
responses at the individual patients’ level to better
comprehend targeted dosing requirements of hypothyroid
patients.
For now, these conflicting observations question the
validity of presently adopted clinical practices. Future
studies on T4 substitution therapy should include addi
tional parameters of peripheral thyroid signaling such as ceruloplasmin or sex-hormone binding globulin, and
quality of life metrics for assessment of neuropsychologic
effects. The utility of bivariate reference regions for FT4
and TSH
personalized T4 substitution via an inferred homeostatic
HPT axis set-point computation from multiple paired
measurements of TSH-FT4 should also be investigated.
I like it , i can't find any mistakes , and i think it makes a clear and compelling case that they should use their brains rather than a formula. I particularly like the emphasis on smaller titrations , and more frequent reviews of those needing to start on a low dose.
The difference between patient 1's 125 mcg and patient 3's 25mcg is truly ridiculous, and it's good to see it clearly spelled out like that.
Having said that , i haven't seen much evidence on the forum of GP's actually using this 'formula'.. if they did we wouldn't see so many middle aged patients stuck on 50mcg for a decade.
It's been whirling around my head since the NICE guidelines were in draft form.
Finally got to typing it out and trying to make a cogent (hopefully!) argument.
Showed 'im indoors the difference in persons 1-4 doses .
He used to work in A&E... his reaction was;
" deleted expletive* , looks like they're just making it up as they go along"
If GPs are using it, then my points are valid.
If GPs are not using it, what are they using instead? It is fine to be selective, intelligently, about guidelines but how can there be such a disjoint between practice by GPs and NICE?
They used it on me at the endocrinologists ☹️I asked them why my sister who is tiny was on 175mcg but me who towers over her was only in 125mcg Levo - no satisfactory explanation was provided. I felt pants on 25, 50, 75, 100, 125 125/100, 150 self medicating and 175 self medicating I gave up and switched to NDT. Once on 1.25 grains - normality was restored. I realised later that thyroid cancer was probably the reason for the dose differential - even that’s been abandoned now in her case 🙄
Thank you!
Excellent discussion could not be agree more. Thanks for this.
Great article - thanks for producing this.The Nice guidelines suggest ‘rounding’ to the nearest 25mcg. Your example of someone weighing 70 or 71 k suggests the latter would be rounded up. Do you think Nice would always ‘consider’ rounding up or would it be rounding down if that was closer?
In working out the examples, I used the ROUND function in Excel, which rounds to nearest - that is, 1.49 rounds down to 1, and 1.50 rounds up to 2.
As I did that, I was pretty comfortable with my interpretation. But I certainly agree someone could easily switch to round down or round up without thinking it through.
In the end, the effect of rounding will be the same, sudden jumps, but the point on the scale at which it occurs would shift.
Not sure what 'formula' they used on me after a sub-total thyroidectomy (9/10ths removed) to arrive at 75 mcg Levothyroxine Hidden . When the Levo was Cox, Norton or Goldshield Eltroxin, it worked quite well. Could not take Actavis at the time and stll could not in 2010, when only generics were available to us. NDT over the past 3 years has worked quite well, only causing a few gastric problems since only being able to hae Erfa. WP NDT worked very well for me.
Why they have removed NDTs from being prescribed in the NHS through False Statements made by the 'experts' I do not understand.
It was the very first replacement that saved lives since 1892 tbut now withdrawn and there's no substitue.
The experts have ignored the fact that many people recovered on NDTs but it seems that 'they' do not care. Why did they become interested in Endocrinology when they don't seem to have any understanding of what helps patients recover their health!
I'm beginning to get seriously worried now shaws , as I do not feel I can go back to Levothyroxine and even with Liothyronine it was not really improving things for me. I really hope that WP Thyroid comes back on the market.
It is so stressful to think that you cannot get the product that helps relieve your clinical symptoms.
I found levo was 'sort of poisoness' for me too as I was far more unwell on this (like many we're ignorant when first diagnosed) than before diagnosis.
Have you tried liothyronine alone? If not and you are aware I'm not medically qualified but I found it beneficial if taken alone. Keeping in mind I'm not medically qualified,
No shaws , I must admit I haven't. A bit scared to try really, plus the cost. Although, NDT has gone up and up, just because they can! Greedy Pharma!
Before I took Lio (T3) I took levothyroxine and was awakened every night with very severe palpitations and husband had to get towels from freezer (that were wet when I put them in, so they were frozen stiff). That helped to reduce palps when I wrapped towels round my neck and I sipped iced water.
The Cardiologist was puzzled about what caused these severe nightly palpitations and was considering putting an implant into my heart to 'see what was going on'. Just about then some T3 was added to T4, palps eased off a lot and when I stopped T4 they disappeared altogether. So my chosen replacement was/is T3 only. I haven't seen the cardiologist since but I have pity for those people whose heartbeat goes crazy with some replacements. We are all so different, i.e. some people cannot eat chocolate, some love it. So I assume it is the same with medications.
Why can some countries produce cheap replacement thyroid hormones but ours, as you indicate, the price that pharma companies charge the NHS seem exorbitant.
This is the relevant bit of the spreadsheet I used.
