Note: I’m a little bit sick today, and it’s possible I made a mistake in my stoichiometry or in converting from math to reasoning. If so, I will happily stand corrected if anybody points out my error.
The change in terminology is just verbiage. In fact, it appears they have narrowed the definition of both subclinical and clinical hypothyroidism in the newer paper. In light of how they changed the definitions, we should think that a definition-neutral rate of both subclinical and clinical hypothyroidism has gone up even more than I’d described in my previous comment.
Hypothyroidism is defined in part by lower-than-normal thyroxine (T4). In the earlier paper, T4 levels are defined as “clinical” that would be defined as “normal” or “subclinical” in the later paper. According to the definitions of the later paper, all “subclinical” patients in the earlier paper would have been considered “normal.”
They switched from measuring bound + unbound thyroxine (T4) to free thyroxine (FT4) in the second paper. So the numbers aren’t directly comparable because they’re measuring the molecule in two different states the body. I don’t know whether we can do more than rely on the researchers’ implied claim that the definitions of normal vs. subclinical vs. clinical hypothyroidism remain comparable under the new definition.
Extracts and calculations for legibility:
’88-’94 paper:
… high T4 is a concentration 169.9 nmol/liter and low T4, a concentration 57.9 nmol/liter...
Hypothyroidism was defined as clinically significant if TSH > 4.5 mIU/liter and T4 < 57.9 nmol/liter and as subclinical or mild when TSH > 4.5 mIU/liter and T4 >= 57.9 nmol/liter...
Subclinical hypothyroidism was defined as having TSH levels ≥ 4.5 mIU/L and FT4 within the normal reference range [of 0.6-1.6 ng/dL]. Those who had TSH levels ≥ 4.5 mIU/L and FT4 below 0.6 ng/dL were defined as having clinical hypothyroidism.
Thyroxine (T4) has molecular weight 776.87 g/mol.
In adults, normal levels of total T4 range from 5–12 micrograms per deciliter (mcg/dl) of blood. Normal levels of free T4 range from 0.8–1.8 nanograms per deciliter (ng/dl) of blood.
I haven’t converted these densities to molarities, so I haven’t compared these ranges with those provided by the ’88-’94 paper, but this distinction seems relevant.
Good catch, I will edit the previous comment tomorrow when I’m on my computer. Given that the sub vs clinical distinction turns on T4/FT4 and these papers test for different values, I’d need to give more thought about how comparable they are.
Note: I’m a little bit sick today, and it’s possible I made a mistake in my stoichiometry or in converting from math to reasoning. If so, I will happily stand corrected if anybody points out my error.
The change in terminology is just verbiage.
In fact, it appears they havenarrowedthe definition of both subclinical and clinical hypothyroidism in the newer paper. In light of how they changed the definitions, we should think that a definition-neutral rate of both subclinical and clinical hypothyroidism has gone up evenmorethan I’d described in my previous comment.Hypothyroidism is defined in part by lower-than-normal thyroxine (T4). In the earlier paper, T4 levels are defined as “clinical” that would be defined as “normal” or “subclinical” in the later paper. According to the definitions of the later paper, all “subclinical” patients in the earlier paper would have been considered “normal.”They switched from measuring bound + unbound thyroxine (T4) to free thyroxine (FT4) in the second paper. So the numbers aren’t directly comparable because they’re measuring the molecule in two different states the body. I don’t know whether we can do more than rely on the researchers’ implied claim that the definitions of normal vs. subclinical vs. clinical hypothyroidism remain comparable under the new definition.
Extracts and calculations for legibility:
’88-’94 paper:
Subclinical hypothyroidism: TSH > 4.5 mlU/L and T4 >= 57.9 nM
Clinical hypothyroidism: TSH > 4.5 mlU/L and T4 < 57.9 nM
’07-’12 paper:
Thyroxine (T4) has molecular weight 776.87 g/mol.
(.6 ng/dL) * (10 dL/L) * (1E-9g/ng) * (1 mol/776.87 g) *(1E9 nmol / mol) = 7.7 nmol/L = 7.7 nM.
Subclinical hypothyroidism: TSH >= 4.5 mlU/L and 7.7 nM ⇐ T4 ⇐ 20.5 nM
Clinical hypothyroidism: TSH >= 4.5 mlU/L and T4 < 7.7 nM
FT4 is not the same thing as T4. From Medical News Today:
I haven’t converted these densities to molarities, so I haven’t compared these ranges with those provided by the ’88-’94 paper, but this distinction seems relevant.
Good catch, I will edit the previous comment tomorrow when I’m on my computer. Given that the sub vs clinical distinction turns on T4/FT4 and these papers test for different values, I’d need to give more thought about how comparable they are.