Measuring thyroid hormone level is a very simple matter in clinical practice. For total T4 you can do it in-house if you don't care too much about accuracy. A commercial lab is better. Very occasionally you meet a patient with very clear cut markers of thyrotoxicosis which has a T4, as measured by a commercial lab, which is persistently within the upper end of the lab reference range for normality.
For these (usually cats) we check the free T4 level. Free T4 is not cheap, despite the name, and takes some time to come through from a referral lab. We use this test because almost all of the total T4 in plasma is bound to albumin and assorted other plasma proteins. We need the "unbound" or active concentration thyroxine because this is what does what it does. Of course no one really wants to measure free T4 anyway, what we want is the actual active hormone, T3. Preferably free T3. However, for many cases, free T4 is good enough.
Measuring T3 or (gasp) even free T3 is another ball game and is something I only request occasionally. Usually when trying to get to the bottom of apparently hypothyroid dogs when all lab results come back "borderline low". Unfortunately free T3 is not available in the UK and sample gets couriered to the USA. I think the courier must swim the Atlantic judging by the time taken.
But ultimately even the free T3 is only a surrogate for the level of T3 which is actually bound to its receptor within the nucleus of each cell, including those of the brain.
Measuring receptor occupancy this is neither easy, clinically appropriate nor commercially available. But fortunately there is a surrogate.
You can get an idea of whether the brain thinks there is enough T3 sitting on its receptors by whether it is asking for more. It asks for more using (eventually, after several steps) TSH, thyroid stimulating hormone. This is released from the pituitary as a signal to the thyroid to increase production.
So the rule of thumb with a suspected hypothyroid patient is to ask whether the TSH level is elevated, ie is the brain unhappy with the current thyroid level. When you don't have the time or finances available for that courier to swim the Atlantic, this is what we use. It's a surrogate, but useful.
As so often, this is just basic clinical chemistry. It defines how I view hypothyroidism.
So let's put some folks on a diet, get them down to 10-15% below their start weight and look at their thyroid status. Keep them as weight stable as you can and look at total T3 levels on three different diets.
Not surprisingly the level of thyroid hormone falls with weight loss. The run-in diet provides weight stability before weight loss and the T3 is 137ng/dl.
The same folks after weight loss, and on 310g/d of carbs, have a T3 of 121ng/dl.
On 205g/d of carbs the T3 is about the same at 123ng/dl. But with carbs restricted to 50g/d of it drops a whopping 29ng/dl to 108ng/dl, twice the drop of the more moderate carb diet phases.
There you have it. Eat LC and thyroid deficiency, here you come.
OK, so the next question is: What does the brain think about all of this? Remember T3 is not free T3 and certainly not nuclear bound T3, so we have to look at the surrogate. What is the message from the brain to the thyroid gland concerning the adequacy (or not) of current thyroid levels? Which way does the TSH, our crude surrogate for effective neuronal nuclear bound T3, shift?
The run-in TSH is 1.15microIU/ml, this is on obese weight stability. It goes up (the Badness direction) to 1.27microIU/ml on high carb, 1.22microIU/ml on moderate carb and it drops (the Happy direction) a gnat's whisker to 1.11microIU/ml on LC.
Summary: Despite the limited fall in T3 on higher carb diets, the brain is not happy with thyroid status. TSH goes up. Gimme gimme gimme, more more more.
However, even with the greater fall in total T3 under LC eating, the brain is happy with whatever level of free T3 it is "seeing", as judged by TSH level. Should the brain be happy?
There are hints. In particular the TEE was reduced least in the LC phase of the study. There was a reduction in TEE of course. But less than for either of the other two phases imposing weight stability at reduced BMI. Despite the largest drop in total T3. It seems like a reasonable idea that both free T3 and receptor bound T3 might actually be higher under LC eating. As so many times, we will never know.
Another way of looking at the change would be to consider whether as much free T3 is needed on a LC diet. Sam Knox provided this rather nice link in the comments to The lost 300 post. It's certainly worth thinking about. Of course, I quite like the idea. But then I would!
So will low carbohydrate eating lead to thyroid deficiency? Who knows, in the long term. This was a very short study. But in this paper the brain seems quite happy with 108ng/dl of total T3 as judged by a TSH of 1.11microIU/ml.
This does not look like hypothyroidism to me.
But then I'm just this clinician see...
And here's an aside on LC eating and 24h urinary cortisol. I'll just stick the key quotes from the discussion:
"As in previous studies, discrepancy between cortisol regeneration measured during dynamic testing and the more conventional index of 24-h urinary endogenous cortisol/cortisone metabolite ratios (Table 2) reflects the confounding effects of 5 alpha- and 5 beta-reductase activities on ratios of steroids excreted in urine."
Translation: Relying on 24h urinary cortisol may mislead you. That might help with LC bashing, but you're still misled.
"Low-carbohydrate intake appears to be the key factor responsible for alterations in glucocorticoid metabolism"
Translation: LC eating is what is KEY to IMPROVING glucocorticoid metabolism.
"...extraadrenal regeneration of cortisol is responsive to the macronutrient content of the diet. In these obese men, a low-carbohydrate diet reversed the increase in metabolic clearance of cortisol (3), increase in 5 alpha- and 5 beta-reductase (4), and decrease in hepatic 11 beta-HSD1 (5, 6) previously described in obesity.
Translation: LC eating reverses the nasty effects of obesity.
"The increase in 11 beta-HSD1 activity, and hence intrahepatic cortisol concentrations, caused by a ketogenic low carbohydrate diet has implications for the efficacy of different dietary strategies in reversing the metabolic consequences of obesity."
Translation: LC eating wins hands down for correcting the metabolic consequences of obesity.
24h urinary cortisol? Pah.