Take Thyroid Function Tests with a Grain of Iodine

Myth: Thyroid function tests in inpatients are reliable markers.

Malady: There are many caveats to routinely testing hospitalised patients asymptomatic of thyroid pathology – namely those acutely unwell, or recent contrast loading (i.e. almost all of them). 

This edition, we take a break from the math and instead delve into thyroid physiology. Yes, there is more to it than “modify dose by 25mcg and repeat TFTs in 4-6 weeks”.

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First, the ever helpful oversimplification of complex physiology through arrows and labels. 

Let’s meet the protagonists for this episode. This is admittedly confusing, and took me a Sunday to understand, but please do bear with me. 

Wolff-Chaikoff effect: An auto-regulatory measure, described in 1944-48, whereby an iodine load suppresses the iodination of thyroglobulin (organification) in a transient fashion. The quoted timeframe of the effect varies, but generally lasts days, after which there is escape from the Wolff-Chaikoff effect due to critically low levels of intrathyroidal iodine. A key player in this process is the sodium-iodide symporter. Those with underlying thyroid abnormalities (despite being clinically euthyroid, or otherwise) may fail to escape from the Wolff-Chaikoff effect resulting in persistent hypothyroidism [1].

Plummer effect: Often confused for the Wolff-Chaikoff effect, the Plummer effect is an adjacent observation whereby higher serum iodine concentrations reduce the secretion of thyroid hormones, mainly via inhibiting proteolysis of already formed thyroglobulin [2]. It serves a similar purpose as the Wolff-Chaikoff effect, but there is no clear escape mechanism and interestingly, seems to be more prominent in hyperthyroid individuals (see Phillipou et al for one study, amongst a few in this topic, that would throw contemporary ethics boards for a spin).

As you can appreciate, these two are very neat evolutionary mechanisms to prevent the fool who ate a fistful of iodine from degenerating into a fibrillating, thyrotoxic mess. A marvellous demonstration of how little faith our body has in itself. The dehalogenase effect doesn’t get a mention because it’s not named after some bearded white guy.

Jöd-Basedow effect or jödbasedow: This effect is iodine-induced hyperthyroidism – the evil child of the triplet. In the traditional sense, it was described as thyrotoxicosis following iodine supplementation in those with pre-existing dietary iodine deficiency, but has been shown to happen in those with iodine sufficient diets [3, 4].

For those who were definitely not wondering, this is not named after a famous Jod – it’s the word for iodine in German which was also why iodine was often denoted with “J” in now ancient periodic tables. Carl Adolph von Basedow on the other hand, is a lesser recognised German version of Graves, and in Europe the term “Basedow’s disease” is apparently more common. This I cannot confirm and you must take my word for, I haven’t travelled for the purpose of straw-polling Germans on thyroid disease.

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Now it may seem that these effects are relegated to the realm of clinically useless, but neat physiological nuggets. To that I raise these real life scenarios where:

• Amiodarone-induced thyroid abnormalities are largely governed by these principles, courtesy of the high iodine content in the molecule, hence the “iod” in its name. These take the flavour of hypo- and hyperthyroidism dependent on factors including baseline thyroid function, dietary iodine availability, and your understanding of physiology – a topic for another day [5]
• The Plummer effect is a known crisis treatment for thyrotoxicosis (usage of Lugol’s iodine) and the effect was first described as a perioperative adjunct for those with Graves’ disease undergoing surgery [6]
• If there is nuclear armageddon, the Wolff-Chaikoff and Plummer effects (along with boring drowning out the radioactive iodine) are main considerations for using iodine tablets to prevent radioactive iodine-induced thyroid toxicity. It follows that if you time the iodine ingestion wrong (after the radioactive iodine is already in the system) you may Plummer yourself into retaining isotopes longer! [7]

Perhaps the most frequent, clinically relevant group with supra-physiological iodine loading we encounter are those who undergo contrast scans. Modern iodinated contrast media agents tend to have higher iodine concentrations than their now-redundant high osmolar, nephrotoxic counterparts. An average CT scan entails around 50-100mls of contrast which translates to around 18-30g of iodine, of which ~7000μg is immediately bioavailable, and a tiny portion of the remainder may be later harvested through deiodination. This is well beyond the tolerable upper limit of iodine at 1100μg/day, and more than 40 times the recommended dietary intake of 150μg/day. Hypothyroidism following contrast is a manifestation of failure to escape from the Wolff-Chaikoff effect, and hyperthyroidism is jödbasedow [4,8]. Previous studies have identified a trend towards thyrotoxicosis as the main outcome.

Thyroid function is no exception to the rule that all homeostatic mechanisms go awry in acute illness, and this has earnt itself the special moniker of ‘sick euthyroid syndrome ‘ which denotes a pattern of TFTs, classically low T3 and normal TSH, in the unwell populace [9]. 

So we have an asterisk against those who get contrast CTs and those who are sick. Taken together, this really questions the role of routine thyroid function tests in inpatients. Take that, “geriatric bloods”. Recent guidelines generally recommend against (or provide no strong reason for) screening asymptomatic individuals [see Canadian Task Force on Preventive Health Care], if no individual risk factors are present. Of course, it is reasonable to still test if thyrotoxicosis or hypothyroidism is a key differential.

If you have the luxury of being able to add on testing to pre-contrast admission bloods, perhaps the result may be more reliable. It may follow that patients with aberrant TFTs on bloods taken after a contrast scan are higher risk of thyroid abnormalities that later become clinically evident – we could take contrast scans as a ‘thyroid stress test’ of sorts and ensure follow up for patients who have abnormal TFTs after contrast. The corollary is that those with existing thyroid funkiness should have an eye on it after contrast scans to ensure it is not misbehaving. 

If thyroid pathology (for the most part) was more difficult to diagnose and less satisfying to treat based on numbers alone, I do wonder if we would test and care less for it. 

Giant’s Shoulders:
[2] A painstakingly detailed review about thyroid hormone physiology
[4] Sohn et al explaining all of this in detail this year, an article I only found after reading a century’s worth of seminal thyroid hormone physiology
[7] Verger et al‘s 2001 review about how the above physiology contributes to potassium iodide dosing in the event of nuclear emergency (may we never need this)

Also cited above:
[1] Markou and colleagues re: iodine-induced hypothyroidism
[3] The trials and tribulations of iodine excess
[5] The only guide to amiodarone-induced thyroid abnormalities you’ll ever need
[6] A 1930 article I am using as evidence of this being a relevant physiological principle
[8] Detailed review of iodinated contrast and its sequelae
[9] Sick euthyroid, or euthyroid sick syndrome reviewed by Lee et al

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