In case we have anyone with cystic fibrosis, or responsibility for someone, this paper which recognises levothyroxine malabsorption might be helpful.
To go a step further, the paper suggests that the malabsorption is "likely due to the combination of pancreatic insufficiency, chronic intestinal inflammation and reduced biliary salts production". Does this support the idea that anyone with suspected malabsorption should be investigated with a view to identifying pancreatic insufficiency, chronic intestinal inflammation and/or reduced biliary salts production - from any cause?
We do see a number of people with unexplained apparent levothyroxine malabsorption.
CYSTIC FIBROSIS AS A CAUSE OF MALABSORPTION AND INCREASED REQUIREMENT OF L-THYROXINE.
Dr. Giuseppe Giuffrida, Prof. Giuseppe Magazzu, Dr. Alfredo Campenni, Dr. Maria Cristina Lucanto, Prof. Francesco Trimarchi, Prof. Salvatore Cannavò, and Dr. Rosaria Maddalena Ruggeri
Cystic fibrosis (CF), a monogenic disease from mutations in the CFTR gene, causes pancreatic and biliary insufficiency with impaired absorption of nutrients and drugs. Unlike other malabsorption disorders, no data are available in literature on levothyroxine (L-T4) absorption in these patients. Herein we report L-T4 malabsorption and increased requirement in two hypothyroid patients with CF. Both patients (patient #1, a 44-years-old female; patient #2, a 39-years-old male), affected by post-surgical hypothyroidism, were unable to reach adequate TSH levels despite a daily L-T4 dosage largely exceeding their weight-estimated values, even after multiple increases. They did not take medications altering L-T4 absorption or metabolism. In both patients an L-T4 absorption test was performed, under clinical control. Serum concentrations of TSH, total (T4) and free-thyroxine (FT4) were measured before ingestion of L-T4, then every hour for 4 h and 24 h later. Area under the curve (AUC) for T4 and FT4 was calculated. After L-T4 load, T4 and FT4 values remained below the lower reference range limit in patient #1; a slight increase towards normal levels, but under a 2.5-fold cut-off was observed in patient #2, thus confirming a true malabsorption in both subjects. The AUC were similar in the two tests. Both patients were then shifted towards liquid L-T4 formulation, reaching stable target TSH ranges. CF should be included among the digestive diseases causing L-T4 malabsorption, likely due to the combination of pancreatic insufficiency, chronic intestinal inflammation and reduced biliary salts production. L-T4 oral liquid formulation allows to overcome the reduced absorption of L-T4 in these patients, in which L-T4 absorption test can confirm a real malabsorption, leading to more tailored choices for hypothyroidism management.
Lactose malabsorption and Helicobacter pylori infection represented the most common disorders, with a global prevalence of 68% and 48%, respectively. The prevalence of other conditions, including autoimmune gastritis, bariatric surgery, celiac disease, gastroparesis, giardiasis, liver cirrhosis, or ulcerative colitis, was lower than 20%. Data at regional and country levels were found to be heterogeneous, but at least one in five patients was diagnosed with one disorder.
So 20% of patients on levothyroxine have malabsorption issues ......seems remarkably similar to the 20 % of patients recognised as having significant difficulties on standard levothyroxine tablets!
I would very much like to see a study which compares various oral levothyroxines against non-oral - e.g. injected, slow release implant, anything else!
I suspect the results would reveal some interesting issues - and possibly not the simple and obvious results as we might predict.
My son and I have developed gastric problems since we were changed frm Goldshield Eltroxin in 2010 to generic Levothyroxine. I have not noticed any change in digestion for the better since I changed to NDT in February 2019 though. thank you helvella and SlowDragon for posting this information.
That is precisely what I think it effectively says. Though there could be a question over whether you need to AND them or OR them. In other words, would any one or two be sufficient to cause malabsorption, or would it be insisted that you need to suffer all three?
I strongly suspect we will have a different opinion to some doctors.
Given a while, I did eventually find references to what I was thinking about.
Levothyroxine is almost insoluble in neutral and acidic solutions. However, it dissolves somewhat better in alkaline solutions. I believe that is why most levothyroxine absorption takes place in the jejunum and ileum.
However, with Exocrine Pancreatic Insufficiency, the gut contents might not become alkaline enough to achieve that absorption. I put this forward in speculation - not demonstrated or proved!
Furthermore, in EPI, due to cystic fibrosis (CF) or chronic pancreatitis, there is decreased bicarbonate output causing a lower intestinal pH, which precipitates bile salt acids and impairs micelle formation of fats.
We have so often read on this forum and elsewhere off the detrimental effect of PPIs on absorption because of the significant elimination of stomach acid and the creation of an alkaline environment which is alien to absorption.
My take is this:
Stomach acidity is an important issue which affects lots of things. It might affect levothyroxine tablets themsleves - as in, they might not disintegrate fully, or similar.
But when it comes to the actual dissolution of levothyroxine, so that it can be absorbed, I am not convinced that acidity itself has any significance.
Maybe, if there is insufficient stomach acid, too little bicarbonate is released so the jujeniuum and ileum are not alkaline enough?
It is so very easy to see why inadequate stomach acidity might be seen as a cause. I am not convinced.
The patent applications for oral levothyroxine solutions (liquid levothyroxine) say that they dissolve the levothyroxine in an alkaline solution, then acidify it. The acidification stabilises the solution (and that fact itself seems to have been a surprise).
I think this discovery is why oral levothyroxine solutions became available. Had levothyroxine dissolved in the acid stomach environment, it would have been trivial to produce either liquids or tablets that dissolve with certainty.
The fact that the absorption peak is about two hours after ingestion corresponds with it occurring when the acidic stomach contents are made alkaline in the intestine. Virtually none being absorbed from the stomach.
Despite only being one iodine atom different, liothyronine is a very different molecule. My reservation about interactions with food, etc., is that too little research has been done. We have seen the number of substances which interact with levothyroxine grow almost month by month over the past ten or twenty years. We really need definitive research not just assumption and best guess.
Thanks linda96 There is CF in the family, so was not surprised to find I’d inherited a significant heterozygous CFTR gene. Looking through genes I also have several homozygous CFTR genes and more heterozygous too. I also have a heterozygous hemochromatosis gene and am aware of some in family. Looking into that I was surprised to find several forms of HFE , all but one is inherited homozygously. One SNP if inherited from both parents can cause damage to organs. The others are managed by giving blood. There is one HFE snp that is dominantly inherited, I believe that means you only need to inherit from one parent. In that case, I have inherited from both. It means nothing much to me at present as I tend to be more on the anaemic side. And I wonder just how much one thing can balance out another.
So I wonder if some of these other CFTR snp polymorthisms don’t have some linked, maybe lesser effects, not as serious as CF but still causing problems blocking up systems in some minor way, causing wider problems.
While we might manage adequate consistency (of make of tablet, of time of taking, of dose, of avoiding food/drinks/supplements/other medicines, etc.), the extra factors are almost impossible to manage. For example, hot days versus cold days, other illnesses - however minor in themselves, fresh versus stored foods, and on and on.
I don't have an answer as to how we could achieve it, but I have long been convinced that the closer we can get to continual monitoring, the better.
Initially it looks as if measurement of thyroid hormones would be ideal. On reflection, I question that - perhaps the effects of thyroid hormones are a better choice? Temperature, pulse, electrical characteristics, how well muscles work, gastric emptying - a ragbag of the physical/chemical features which can realistically be measured.
After all, we can read that the effects of T3 can continue for two days (maybe longer?), way after the blood levels have dropped.
If we could monitor really closely for a while, I suggest possibly for weeks, we might see patterns emerge, or that we are stable. If the measurements are not entirely automatic, we might then be comfortable dropping frequency.
(Minor correction, levothyroxine tablets disintegrate and disperse in the acid stomch - but the levothyroxine hardly dissolves.)
If someone who is responsible knew of interactions between T3 and, say, foods, I'd like to think they would change the details.
However, for levothyroxine, they say:
dose to be taken preferably at least 30 minutes before breakfast
I know of no proper evidence that mornings are any better than bed-time. Nor do I believe that 30 minutes is adequate when we consider what people might eat for their breakfasts! Furthermore, where they mention interaction between levothyroxine and ferrour fumarate, sulphate, etc., they fail to point out the same interactions would occur with iron-fortified cereals.
I notice that levothyroxine interactions do not include lithium and liothyronine. Hmmm...
If no-one has researched whether pickled unicorn interacts with liothyronine, I doubt we would see any mention.
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Do you take your thyroid meds in the morning or at night?
