Many blogs updated!

Just a short note to say that many of my blogs have been updated. Sometimes very small things like corrections of typos. Often slightly more such as ensuring the links work. But the biggest in the past few days have been:

Removing almost all the links at the right side of the blog. The type was too small - making them difficult to read. I have instead created this:

helvella - Index of Blog Pages

The same information but in larger text and not repeated everywhere.

helvella - Thyroid Hormone Medicines

Where I have redone the entire UK document and therefore made corresponding changes to this blog entry. In time, I'll be reworking the rest of the world documents but that will take some time.

Dr Pete Taylor’s Fund Thyroid Research Petition 📣🔔🔊💬

📣 Are you on Threads? Or Mastodon? Or Tribal? Or facebook? Bluesky Social? Or Diaspora? Or Counter.Social? Or Reddit? Or Tik Tok? Or Instagram? Or any other “social” site where information about this petition can be posted?

📣 Can you add a note to emails you send?

📣 Do you have your own blog or website where you can add a plug for this petition?

📣 Obviously, don’t become a pain by excessive repetition. But bear in mind that right here we have had at least three posts within the first day! So, within the limits of tolerability, do repeat post – and extend those repeats over the six months that the petition will run.

📣 Quote from existing posts. Or make up your own wording.

Dr Pete Taylor's original post on twitter:

❝Pete Taylor @DrPeteTaylor

Lovely people please could you sign this petition and share widely. Thyroid disease does not get sufficient funding despite being very common, this may help address this -Thx❞

Wording of actual petition on government petition site:

❝Give more funding for thyroid research and patients after price hike

A fine of £84 million has been levied for the price hike in liothyronine (T3), which had a significant impact on patients. We request that an amount equivalent to a proportion of the fine (1-5%) is made available for thyroid research and support for patients with hypothyroidism.

Hypothyroidism is one of the commonest conditions in the UK. However 10-15% of patients despite levothyroxine treatment have persistent ill health, although some find their symptoms improve dramatically with liothyronine (another thyroid hormone). Despite being a common problem hypothyroidism has not attracted research funding and there have been no new treatments in decades. More funding for research and patient support might revolutionise the treatment and lives of many patients.❞

Parliamentary petition for more thyroid research funding

https://healthunlocked.com/thyroiduk/posts/149940446/parliamentary-petition-for-more-thyroid-research-funding

Please sign this petition!

https://healthunlocked.com/thyroiduk/posts/149938874/please-sign-this-petition

Give more funding for thyroid research and patients after price hike

https://healthunlocked.com/thyroiduk/posts/149938613/give-more-funding-for-thyroid-research-and-patients-after-price-hike

This is a direct link to the petition:

https://petition.parliament.uk/petitions/642233

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The Micawber approach to thyroid hormone doses

Charles Dickens, Micawber and thyroid dosing

Mr Micawber's famous, and oft-quoted, recipe for happiness:

"Annual income twenty pounds, annual expenditure nineteen [pounds] nineteen [shillings] and six [pence], result happiness. Annual income twenty pounds, annual expenditure twenty pounds ought and six, result misery."

If you take 100 micrograms of levothyroxine a day and your body expends 99 micrograms, result happiness. Take 100 micrograms of levothyroxine a day, body expends 101 micrograms, result misery.

Every extra day leaves you further behind, until eventually you reach a new but definitely suboptimal steady state. A tiny, tiny amount more than you need is of little or no consequence.

For example, if you were on 125 micrograms and needed a small dose reduction, say to 112, but you were actually reduced to 100, you would be falling behind by 12 micrograms a day. In one week, you are down by 84 micrograms. Only when your body reduces its "consumption" of levothyroxine to 100 can the new steady state occur - and you will be well down by then.

(Be careful not to interpret this as an invitation to take more and more levothyroxine, that is taking the analogy too far.)

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Private Prescription Charges

If you ever get issued with a private prescription, Stop! Consider how much it will cost to get the item dispensed

First, is the item actually prescription-only? If it is available over-the-counter, that will almost certainly be the cheapest option.

What is the actual price of the medicine?

The pharmacy will likely have a range of possible suppliers with a range of prices. Then discounts depending on all sorts of factors. That makes it very difficult to get the exact price. But you can often get an idea from the British National Formulary.

https://bnf.nice.org.uk/

NHS pay the pharmacy through an agreed reimbursement mechanism based on the NHS Drug Tariff.

NHS also pays a dispensing fee (something like 245.0 through 286.8 per item depending on prescription).

NHS Drug Tariff prices for amitriptyline range from 75 through 98 pence per 28 (depending on dosage). Actually very similar prices to most levothyroxine tablets.

A pharmacy might charge £9.65 might is simply a base price equal to NHS prescription charge.

For example:

For private prescriptions you've obtained from another GP, we have a minimum dispensing charge of £9.65 per item.
https://www.pharmacy2u.co.uk/prescriptions/

I've never seen anything that stops pharmacies charging whatever they want for private prescriptions. But maybe there is some sort of price control mechanism?

Find the cheapest private prescriptions 

While NHS prescription prices are fixed, pharmacies can set their own for private prescriptions. These are given when you want a drug not covered by the NHS in your region, such as Malarone to prevent malaria if you're travelling and some cancer drugs. 

It could be a drug for a lifestyle-enhancing purpose, such as sexual aid Viagra (although this can be on the NHS if your erectile dysfunction's caused by a medical problem, such as diabetes, prostate cancer or a kidney transplant) or anti-baldness drug Propecia. 

Non-NHS doctors can't give NHS prescriptions. So go to one for emergency weekend diagnosis, or because you're a member of a scheme, and you'll get a private prescription.

Always compare prices 

Unlike the world of NHS prescriptions, with private prescriptions it's an open marketplace and pharmacies can set their own prices, meaning costs vary hugely. 

The table below shows how prices can vary for just one item, but it can be an even bigger difference if you ask for the generic version.
https://www.moneysavingexpert.com/family/cheap-prescriptions/

Note: NHS prescription charges only apply in England and even then only if you do not qualify for exemption.

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helvella - Thyroid USP

The Standard

Thyroid USP is, first, a standard. The U.S. Pharmacopeia defines medicine standards for the USA. And some countries follow USP standards, especially when there are few, if any, other standards for something.

The Products

Secondly, Thyroid USP is the substance produced that conforms to the USP standard.

And on the Thyroid UK forum, we do try to use the terms Natural Desiccated Thyroid (NDT) and Desiccated Thyroid Extract (DTE) solely for products which conform to USP. Sometimes this results in admin action to ensure consistency of information.

Products which do not claim to be Thyroid USP tend to be called "thyroid glandulars" as we don't really have any other suitable term.

The current Thyroid USP standard is not readily accessible. Which makes it difficult to say anything definitive. Some of what follows is historic and might no longer be true.

Discussion

Nothing in USP demands that the animal source is porcine. It could be bovine (cattle) or ovine (sheep). But I am not aware of ANY Thyroid USP product which isn't porcine. Though there are at least a few bovine glandular products.

The USP standard was originally devised to try to ensure consistency of the product but the chemical assay techniques were nothing like as refined and capable as those now available. The standard checked the amount of iodine which was bound - and assumed that represented thyroid hormone.

More recently it has been revised to use techniques which specifically check levothyroxine and liothyronine content much more directly.

 Further, in general we rely on the manufacturer's claims. For USA products, we know the FDA is involved. Similarly the relevant agencies for Canada and any EU countries.

The current official Thyroid USP monograph is not readily accessible. The link below claims to be the version from 2007 but this cannot be verified.

http://pharmacopeia.cn/v29240/usp29nf24s0_m83400.html

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Transdermal Levothyroxine

The possibility of delivering levothyroxine avoiding the digestive system has many advantages. These include interference with food, drinks, other medicines, supplements, etc. Also the possible effects of levothyroxine on the gut ling and biome.

It will take years of research for any products to reach market. Even then, most novel medicines, even if just a different route of delivery, cost considerably more than existing products. Therefore access will be limited by wealth of countries and, within countries, wealth of patients or other funding mechanisms

To this end, there have been a number of trials of possible ways of delivering levothyroxine transdermally.

I used the following search (which will return updated results each time it is run).

 https://europepmc.org/search?query=transdermal%20levothyroxine

The most obvious results of interest were:

Film-Forming Systems for Dermal Drug Delivery

 Film-forming formulations represent a novel form of sustained release dermatic products. They are applied to the skin as a liquid or semi-solid preparation. By evaporation of the volatile solvent on the skin, the polymer contained in the formulation forms a solid film. Various film-forming formulations were tested for their water and abrasion resistance and compared with conventional semi-solid formulations. Penetration and permeation studies of the formulations indicate a potential utility as transdermal therapeutic systems. They can be used as an alternative to patch systems to administer a variety of drugs in a topical way and may provide sustained release characteristics.

https://europepmc.org/article/MED/34201668

Levothyroxine sodium loaded dissolving microneedle arrays for transdermal delivery.

Levothyroxine (LT-4) sodium has shown variable bioavailability following oral administration. This can be assigned to the significant influence of gastrointestinal conditions, food and drugs administered concomitantly on the rate and extent of absorption from the gastrointestinal tract. Thus, the aim of this research study was to establish an efficient transdermal delivery system of LT-4 sodium via the application of hyaluronic acid dissolving microneedles. Microneedles-based drug delivery system consists of sharp-tip needles that puncture the top layers of the skin in a minimally invasive manner to create physical channels through which therapeutic molecules can easily diffuse into/across the skin. Hyaluronic acid polymer at different ratios (5-60 %) was used to prepare microneedle arrays (100 needles per array) using a micromoulding technique. Characterisation tests were carried out to select the optimum formulation. F11 formula containing 50% w/v hyaluronic acid and 1% v/v Tween 80 formula showed an appropriate needle shape with dimensions of 432 ± 6.4 μm in height and a tip diameter of 9.8 ± 1.3 μm. The microneedle arrays demonstrated a suitable mechanical strength after applying a force of 32 N per array and an excellent insertion ability both in Parafilm M® and human skin. The in vivo dissolution of microneedles was started rapidly within 5 minutes following the insertion in the skin and completed at 1 hour. Ex vivo permeation study using human skin has shown a significant improvement in LT-4 sodium delivery across the skin compared to control preparations (drug solution and microneedle free film). The microneedle array F11 has significantly (P ≤ 0.05) increased LT-4 sodium permeation through the skin (cumulative permeated amount of 32 ± 2 μg/cm2) in comparison to the control solution (cumulative permeated amount of 0.7 ± 0.07 μg/cm2) and the microneedle free film (cumulative permeated amount of 0.1 ± 0.02 μg/cm2) over 7 hours. The findings from the irritation test revealed that mild erythema was produced from the application of microneedle arrays which disappeared within 24 hours. Accordingly, dissolving hyaluronic acid microneedles could be a feasible and effective approach to delivering LT-4 sodium transdermally without causing significant skin damage.

https://europepmc.org/article/MED/36131889

Levothyroxine: Conventional and Novel Drug Delivery Formulations.

Although levothyroxine is one of the most prescribed medications in the world, its bioavailability has been reported to be impaired by many factors, including interfering drugs or foods and concomitant diseases, and persistent hypothyroidism with a high dose of levothyroxine is thus elicited. Persistent hypothyroidism can also be induced by noninterchangeability between formulations and poor compliance. To address these issues some strategies have been developed. Novel formulations (liquid solutions and soft gel capsules) have been designed to eliminate malabsorption. Some other delivery routes (injections, suppositories, sprays, and sublingual and transdermal administrations) are aimed at circumventing different difficulties in dosing, such as thyroid emergencies and dysphagia. Moreover, nanomaterials have been used to develop delivery systems for the sustained release of levothyroxine to improve patient compliance and reduce costs. Some delivery systems encapsulating nanoparticles show promising release profiles. In this review, we first summarize the medical conditions that interfere with the bioavailability of oral levothyroxine and discuss the underlying mechanisms and treatments. The efficacy of liquid solutions and soft gel capsules are systematically evaluated. We further summarize the novel delivery routes for levothyroxine and their possible applications. Nanomaterials in the levothyroxine field are then discussed and compared based on their load and release profile. We hope the article provides novel insights into the drug delivery of levothyroxine.

https://europepmc.org/article/MED/36412275

Preparation and in vitro evaluation of injectable formulations of levothyroxine sodium using in situ forming hydrogel temperature-responsive systems based on PLA-PEG-PLA and PLGA-PEG-PLGA triblock copolymers.

Objectives

Recently, great attention has been paid to developing new drug delivery systems to manage the rate, time, and site of drug release. We aimed to design a novel drug delivery system to support targeted and gradual delivery of levothyroxine sodium.

Materials and methods

The triblock copolymers of PLA-PEG-PLA and PLGA-PEG-PLGA were constructed using the ring-opening copolymerization method and then purified and characterized by 1H-NMR, DSC, and GPC techniques. The phase transition temperature of the polymers was determined, and levothyroxine sodium stability was investigated in a phosphate-based buffer (pH 7.4). In vitro drug release into the PBS was measured at different concentrations of the triblocks for one month.

Results

The results of NMR and GPC showed successful fabrication of the copolymers with low molecular weight dispersion and Tg points of -8.19 °C and -5.19 °C for PLA-PEG-PLA and PLGA-PEG-PLGA, respectively. Stability tests showed that during one month, most of the triblocks' masses degraded at 37 °C while levothyroxine sodium remained stable. Initial burst release of the drug in both copolymers is inversely correlated with the concentration of the polymer. Evaluation of drug release for 35 days showed that PLA-PEG-PLA had a slower drug release rate than PLGA-PEG-PLGA.

Conclusion

Considering the low initial burst release, as well as continuous and long-term release kinetics of PLA-PEG-PLA and PLGA-PEG-PLGA copolymers, they can be used to gradually deliver levothyroxine sodium, obviating the need for frequent administrations and concerns over drug-food interactions.

https://europepmc.org/article/MED/35656181

Transdermal Delivery Systems for Biomolecules.

Purpose

The present review article focuses on highlighting the main technologies used as tools that improve the delivery of transdermal biomolecules, addressing them from the point of view of research in the development of transdermal systems that use physical and chemical permeation enhancers and nanocarrier systems or a combination of them.

Results

Transdermal drug delivery systems have increased in importance since the late 1970s when their use was approved by the Food and Drug Administration (FDA). They appeared to be an alternative resource for the administration of many potent drugs. The first transdermal drug delivery system used for biomolecules was for the treatment of hormonal disorders. Biomolecules have been used primarily in many treatments for cancer and diabetes, vaccines, hormonal disorders, and contraception.

Conclusions

The latest technologies that have used such transdermal biomolecule transporters include electrical methods (physical penetration enhancers), some chemical penetration enhancers and nanocarriers. All of them allow the maintenance of the physical and chemical properties of the main proteins and peptides through these clinical treatments, allowing their efficient storage, transport, and release and ensuring the achievement of their target and better results in the treatment of many diseases.

https://europepmc.org/article/MED/33425065

If any more interesting papers are published, I'll happily add them to this blog if you tell me about them.

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Red Yeast Rice

This blog post has been replaced by this page:

https://helvella.blogspot.com/p/helvella-red-yeast-rice.html

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Milk Thistle - Silymarin and Silychristin

We need to be careful regarding Milk Thistle. There have been many claims for Milk Thistle over the years. Often suggested for people with liver-related issues.
 
But the only person I know who tried it felt unwell from taking it. So I have long been cautious.

This is a long and detailed page by Tania S. Smith, PhD,on the excellent Thyroid Patients Canada site which explains the issues and specific circumstances in which it should be avoided.

If you are considering taking Milk Thistle it really is worth some time reading this first.

Milk thistle alters thyroid hormone transport
January 16, 2022

https://thyroidpatients.ca/2022/01/16/milk-thistle-thyroid-transport/
 
This paper identifies a potentially significant issue with a constituent of Milk Thistle.
 
Endocrinology . 2016 Apr;157(4):1694-701.
 doi: 10.1210/en.2015-1933. Epub 2016 Feb 24.

Silychristin, a Flavonolignan Derived From the Milk Thistle, Is a Potent Inhibitor of the Thyroid Hormone Transporter MCT8

Jörg Johannes 1 , Roopa Jayarama-Naidu 1 , Franziska Meyer 1 , Eva Katrin Wirth 1 , Ulrich Schweizer 1 , Lutz Schomburg 1 , Josef Köhrle 1 , Kostja Renko 1
Affiliations
•    PMID: 26910310
•    DOI: 10.1210/en.2015-1933
Abstract
Thyroid hormones (THs) are charged and iodinated amino acid derivatives that need to pass the cell membrane facilitated by thyroid hormone transmembrane transporters (THTT) to exert their biological function. The importance of functional THTT is affirmed by the devastating effects of mutations in the human monocarboxylate transporter (MCT) 8, leading to a severe form of psychomotor retardation. Modulation of THTT function by pharmacological or environmental compounds might disturb TH action on a tissue-specific level. Therefore, it is important to identify compounds with relevant environmental exposure and THTT-modulating activity. Based on a nonradioactive TH uptake assay, we performed a screening of 13 chemicals, suspicious for TH receptor interaction, to test their potential effects on THTT in MCT8-overexpressing MDCK1-cells. We identified silymarin, an extract of the milk thistle, to be a potent inhibitor of T3 uptake by MCT8. Because silymarin is a complex mixture of flavonolignan substances, we further tested its individual components and identified silychristin as the most effective one with an IC50 of approximately 100 nM. The measured IC50 value is at least 1 order of magnitude below those of other known THTT inhibitors. This finding was confirmed by T3 uptake in primary murine astrocytes expressing endogenous Mct8 but not in MCT10-overexpressing MDCK1-cells, indicating a remarkable specificity of the inhibitor toward MCT8. Because silymarin is a frequently used adjuvant therapeutic for hepatitis C infection and chronic liver disease, our observations raise questions regarding its safety with respect to unwanted effects on the TH axis.
 
Full paper accessible here:
 
https://academic.oup.com/endo/article/157/4/1694/2422745?login=false

There has long been the received wisdom that T3 does not cross the placenta. I am not aware this has been proved in any level of detail.
 
This paper appears to make that look wrong.
 
Indeed, it appears to identify specific pharmaceutical agents which directly and significantly affect T3 transport.
 
Silychristin is a constituent of Milk Thistle extract and its impact suggests that it should be avoided in pregnancy - and possibly other circumstances.
 
 ThyroidVol. 32, No. 9 Thyroid Economy: Regulation, Cell Biology, and Thyroid Hormone Metabolism and ActionOpen AccessCreative Commons license

Thyroid Hormone Transporters in a Human Placental Cell Model

Zhongli Chen,
A.S. Elise van der Sman,
Stefan Groeneweg,
Linda Johanna de Rooij,
W. Edward Visser,
Robin P. Peeters, and
Marcel E. Meima
Published Online:14 Sep 2022 https://doi.org/10.1089/thy.2021.0503
•    Sections
•    View article
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Abstract

Background: Fetal brain development in the first half of pregnancy is dependent on maternal thyroid hormone (TH), highlighting the importance of trans-placental TH transport. It is yet unclear which transporters are involved in this process. We aimed to identify the major TH transporters in a human placental cell model (BeWo cells).

Methods: Messenger RNA expression of the known TH transporters (the monocarboxylate transporter [MCT]8, MCT10, the L-type amino acid transporter [LAT]1, LAT2, the organic anion transporting peptide [OATP]1A2 and OATP4A1) in BeWo cells and human placenta were determined by quantitative PCR. To determine the specificity and efficacy of transporter inhibitors, we first determined TH uptake at different inhibitor concentrations in African green monkey kidney fibroblast-like cells (COS1 cells) overexpressing TH transporters. We then tested TH uptake in BeWo cells in the presence or absence of the optimal inhibitor concentrations.

Results: All tested TH transporters were expressed in human term placentas, whereas MCT8 was absent in BeWo cells. Both 2-amino-2-norbornanecarboxylic acid (BCH) and L-tryptophan at 1 mM inhibited LATs, whereas at the highest concentration (10 mM) L-tryptophan also inhibited MCT10. Verapamil inhibited OATP1A2 and less efficiently both MCTs, but not LATs. Both rifampicin and naringin reduced OATP1A2 activity. Finally, silychristin inhibited MCT8 at submicromolar concentrations and OATP1A2 partially only at the highest concentration tested (10 μM). In BeWo cells, verapamil reduced triiodothyronine (T3) uptake by 24%, BCH by 31%, and 1 mM L-tryptophan by 41%. The combination of BCH and verapamil additively decreased T3 uptake by 53% and the combination of BCH and 10 mM L-tryptophan by 60%, suggesting a major role for MCT10 and LATs in placental T3 uptake. Indeed, transfection of BeWo cells with MCT10-specific small interfering RNA significantly reduced T3 uptake. Only the combination of BCH and verapamil significantly reduced thyroxine (T4) uptake in BeWo cells, by 32%.

Conclusions: Using pharmacological inhibitors, we show that MCT10 and LATs play a major role in T3 uptake in BeWo cells. T4 uptake appears independent of known TH transporters, suggesting the presence of, currently unknown, alternative transporter(s).
 
Full paper accessible here:
 
https://www.liebertpub.com/doi/10.1089/thy.2021.0503

And this is a search for other Thyroid UK (HealthUnlocked) posts about Milk Thistle.

https://healthunlocked.com/thyroiduk/search/posts?query=milk%20thistle&page=1

 

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MHRA Products Database

 All medicines which are approved in the UK have their documentation posted on the MHRA's products database.

That includes

Summary of Product Characteristics (SPC)

Patient Information Leaflet (PIL)

Public Assessment Reports (PAR)

 https://products.mhra.gov.uk/

(Where the product is available due to approval within the EU, some documents will not be available here.)

It has a search facility but that is very crude and it is difficult to get just want you want. You can include active ingredients, excipients (inactive ingredients), PL numbers, etc. But you can't be clever and search for "levothyroxine that doesn't contain lactose".

It will also list all products which say there are any interactions or warnings about taking while already taking levothyroxine.

Therefore, you would very often want to choose only the Patient Information Leaflet (PIL) documents, and the PL number or active ingredient. Then have to work your way through the documents it finds.

And, if you search for "levothyroxine", you'll probably find all the documents for liothyronine as well - because they include words like "stronger than levothyroxine".

While it is the only complete source of documents, it is tedious to use.

If you find anything incorrect, misleading, typos, links that don’t work, etc., please let me know. Go to my profile and use the contact details there:

https://www.blogger.com/profile/17095075774834042563

Whole Genome Sequencing

The reading of our individual entire genome is known as Whole Genome Sequencing (WGS).

Having been sequenced, the data then needs to be analysed and viewed for it to have any use.

Several companies offering Whole Genome Sequencing at a range of prices.

Be very aware of exactly what they will sequence (will it include maternal DNA?).

Also, what analysis options they offer. Some make available numerous options but they might charge for each additional analysis they add.

Most make it easy to download your sequencing data, if you wish. However, you have to understand what you can then do with it!

It is also important to understand the legal, ethical and, emotional/psychological issues that this sequencing can cause.

This is a list of companies and links. Nothing here should be taken as making any comment about them, their testing, charging, etc. It is simply a partial list of companies. Some might not even offer direct to customer packages.

Under some circumstances, the UK's NHS will run WGS on individuals.

Dante
https://www.dantelabs.com/

Sequencing
https://sequencing.com/

Nebula
https://nebula.org/whole-genome-sequencing-dna-test/

Illumina
https://www.illumina.com/

Veritas
https://www.veritasgenetics.com/

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Suppressed TSH

The technology that went into producing the TSH test was impressive. They were detecting a truly tiny amount of TSH in a small (but massively larger) amount of blood.

Early TSH tests would be able to detect when TSH was low. They simply were not sensitive enough to identify the differences between the various degrees of "low".

The term "suppressed TSH" has come to mean one of a number of different (and inconsistent) things:

Any value of TSH below the lower reference interval. E.g. on a typical TSH test with an RI of 0.4 to 4.5, any value below 0.4.

Any value of TSH below the lowest measurable TSH on the specific assay used. A TSH test will be reported as something like < 0.01 - meaning lower than 0.01.

An arbitrary value of TSH below lower reference interval and the lowest measurable TSH.

Even if we assume that TSH does indeed drop as thyroid hormone levels rise, there is a problem.

A result that is below measurable TSH does not, cannot, show any difference between someone who has high thyroid hormone levels, but possibly still inside their reference intervals, and someone else who has thyroid hormone levels which are far, far higher - maybe double or more.

Yet many published papers treat all those with suppressed TSH as if they have significantly excess thyroid hormone. This wrongs to those who have acceptable thyroid hormone levels but are pushed to reduce thyroid hormone doses. And it also wrongs to those who really do have high thyroid hormone levels by diluting the pool and under-representing the potential severe symptoms they have or could develop.

If you find anything incorrect, misleading, typos, links that don’t work, etc., please let me know. Go to my profile and use the contact details there:

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Hyperthyroid, over-active, over-medicated, etc.

There is a fundamental problem with the language used for these issues which causes much confusion.

If someone's thyroid gland produces too much thyroid hormone, that person suffers symptoms. There are many symptoms which are widely regarded as being common and are often clear enough to diagnose the person as having too much thyroid hormone.

The term hyperthyroid is likely to be applied to the person.

But does hyperthyroid mean that the person's thyroid is producing too much thyroid hormone? Or that the person is suffering the symptoms of having too much thyroid hormone in their bloodstream and cells? Or does it only apply when both occur together?

Broadly, there are three mechanisms which cause the thyroid to produce too much thyroid hormone.

● Some form of nodule or tumour which escapes control and produces thyroid hormone regardless the level of TSH.

● Or the immune system produces TSH-receptor antibodies which stimulate the thyroid gland regardless TSH level.

● Or the pituitary produces excess TSH.

Two of those don't even imply that the thyroid itself is a cause. And even nodules and tumours are often confined to a very small part of the thyroid gland.

An excess of thyroid hormone medication can produce many of the same symptoms.

Unfortunately, hyperthyroid is used indiscriminately. And rarely is care taken to distinguish between the "hyper" prefix being applied to the thyroid gland itself and the level of thyroid hormone in the blood and body.

And people who are being properly treated, and have acceptable blood thyroid hormone levels, are also termed hyperthyroid. 

Similarly, over-active is also used indiscriminately, being applied to both a thyroid gland that is producing too much thyroid hormone and the reaction of the person's body to having too much thyroid hormone.

In the literature you can find use of the term hyperthyroxinaemia. Which means "too much thyroid hormone in the blood". But it is rarely used - too long, too difficult to spell and pronounce, and can look like nit-picking pedantry.

(To be completist, there are some other rare issues which can cause excess thyroid hormone in the bloodstream. Such as ectopic thyroid tissue or physical damage to the thyroid gland.)

My view:

The language needs to be reviewed. The main reason being to make everything clear and well-defined.

We need words for:

● Too much thyroid hormone in the blood, whatever the cause.

● The thyroid gland producing too much thyroid hormone due to an issue within the thyroid - an autonomous nodule or tumour.

● The thyroid gland producing too much thyroid hormone due to an issue in its stimulation - excess TSH or TSH-receptor stimulation by antibodies.

A few suggestions:

Some sensible, some rather less so.

hyper-TH 

Too much thyroid hormone however caused. With the obvious possibility of being extended to the terms hyper-T4 and hyper-T3, if that is seen to be sensible.

Any form of over-medication by thyroid hormone would fit this definition.

While we would usually establish a hyper-TH state by doing blood tests, it needs to be understood that the words themselves do not define that.

It is hyper-TH which causes the symptoms of Graves disease, or a period of higher thyroid hormone release in Hashimoto's (due to damage to the thyroid), or over-medication, or an autonomous nodule or tumour.

hyper-TH is a state. It is always secondary and would usually need to be qualified as being due to something else.

Rather than being a criticism, that actually helps. It allows the state to be discussed even before the cause has been identified. And that is most particularly helpful when there could be multiple factors.

There is still the issue of those who need unusually high thyroid hormone levels - such as thyroid hormone resistance or impaired sensitivity to thyroid hormones. It isn't hyper-TH if it is what the individual needs.

(Imagine a Graves patient on block-and-replace. The hyper-TH state could be due to the Graves disease being out of control, or the replacement dose of levothyroxine being too high, or both.)

TH-hyper-genesis or TH-hyper-secretion

Where the thyroid gland is creating or releasing an excess of thyroid hormone. This can be split into intrinsic (where the cause is within the thyroid gland) and extrinsic (where the cause is the control mechanisms). Again, allowing T4 and T3 variations, if needed.

(The word hyper-secretion is already widely used in medicine. But a simpler option might be preferable. Quite simply, I have not come up with a better term.) 

This also allows that an individual who has a TH-hyper-secretion issue can, when treated (e.g. by an anti-thyroid medicine), not be hyper-TH.

However, because it defines a process, it is sensible to consider people as having TH-hyper-secretion even while being adequately treated. It means that the person has a problem which, if untreated, results in secreting too much thyroid hormone.

If you are hypothyroid, don't feel left out. The same basic principles apply and the words surrounding that also need to be reviewed.

Other suggestions would be welcome. I'm not a linguist. I'm not a medic. But I have seen an awful lot of confusion due to the current language.

Summary:

Hyper-TH - which includes Hyper-T4 and Hyper-T3, if these have been determined and are relevant. 

TH-hyper-secretion - which includes T4-hyper-secretion and T3-hyper-secretion.

This divides in two depending on whether the causative factors are within the thyroid (intrinsic), or outside (extrinsic).

Intrinsic TH-hyper-secretion (again with T4 and T3 forms, if needed).

Extrinsic TH-hyper-secretion (again with T4 and T3 forms, if needed).

Obviously, it is possible for the TH-hyper-secretion be caused by a combination of intrinsic and extrinsic factors.

My suggestions also avoid focus on low TSH as an indicator of excess thyroid hormone. While it sometimes does help, it also confuses if there is an excess of TSH - as from a TSHoma (a small benign tumour that produces TSH).

Other words may be added in order to further refine the description. Such as autoimmune for Graves disease, benign for non-cancerous tumours, etc.

Other Languages

I'd hope that any future terms are chosen so as to make them more readily translatable than some current words and phrases.

Comments

Please feel free to comment. I'd really like to achieve a reasonable level of consensus. And accuracy. I will be happy to make changes, corrections, improvements as needed.

If you find anything incorrect, misleading, typos, links that don’t work, etc., please let me know. Go to my profile and use the contact details there:

https://www.blogger.com/profile/17095075774834042563

Writing a prescription for Aristo levothyroxine

This blog post has been replaced by a blog page which includes all the information that used to be here:

https://helvella.blogspot.com/p/helvella-prescribing-aristo.html

If you find anything incorrect, misleading, typos, links that don’t work, etc., please let me know. Go to my profile and use the contact details there:

https://www.blogger.com/profile/17095075774834042563

Thyroid Calculators

Just added a page with screenshots, links and QR codes for the Thyroid UK blood test calculators.

Nothing new - just easy links to them:

https://helvella.blogspot.com/p/helvella-thyroid-calculators.html

Historical Pages

The history of thyroid treatment has two phases - all history up to George Murray. And onwards from that first use of thyroid gland to successfully treat hypothyroidism.

That was such a profound change. We cannot connect what happened before to what happened after. It is complete separation of treatment. Therefore we have to consider that the history of thyroid treatment is in these two separate phases. Of course, nothing is quite as simple as that. Just because treatment by thyroid extract of various sorts started with George Murray, tt doesn't mean everything change around the world at the same time. Inevitably it took a long time for the treatment to become regularised and standardised, and for the products available. It also took a long time for the treatment to move from the UK around the world an be available to everyone.

These documents primarily consider post-George Murray treatment of myxoedema, but some of the thyroid hormone treatments that were used in the UK are discussed in the historical context of the treatment in the UK. Further, some of the documents report the change from desiccated thyroid, which is more or less what we ended up with thanks to George Murray, to the synthetic products that we have today.

Perhaps the most interesting change since Murray was when Dr Richard Asher wrote his paper, Myxedematous Madness, in which he explained and discussed the treatment of multiple patients at the Central Middlesex Hospital for serious, indeed severe myxoedema, and the profound effect that this had on their mental state as well as their physical bodies. It is something that has been mentioned from the early days, including by people like Dr Hertoghe, but it was not something that had been written up clearly and well.

The fact that Dr Richard Ashcroft managed to treat these patients and see such changes is a testament to his dedication. The paper appears to have had a major effect at the time, indeed several papers, shortly after his original paper, which refer to Myxedematous Madness in various ways, had a major effect. Unfortunately, in these days of treating an awful lot of mental illness by tablet, the basis of mental issues in hypothyroidism have been widely ignored. This is partly because it is unusual nowadays to see profound hypothyroidism myxoedema, despite poor treatment. We do actually see people getting some treatment which prevents that happening very often, but few ordinary doctors in the UK or elsewhere seem to understand the immense impact that thyroid has on the mind And it is an impact but cannot be resolved by anything other than adequate treatment of the thyroid issue. People might need other things as well but they certainly have to have adequate thyroid hormone treatment. Going back to Dr Richard Asher's original paper. I hope emphasises that he was dealing with these issues which other doctors in the country understood existed but had not seen fit to treat with thyroid hormone.

• Dr. E. HERTOGHE on Chronic Benign Hypothyroidism
• Dr Richard Asher - Myxoedematous madness
• helvella - Animal Thyroid in The British Pharmaceutical Codex of 1907
• helvella - Historical Context of Thyroid Treatment in the UK
• helvella - History of Thyroid Hormone Medicines in the UK
• helvella - The End of Thyroid BP
• The First Treatment of Myxoedema in County Londonderry
• THE LIFE-HISTORY OF THE FIRST CASE OF MYXOEDEMA TREATED BY THYROID EXTRACT

 

New page on Scheduling Blood Draws

 Have just posted a new page:

helvella - Scheduling Blood Draws

https://helvella.blogspot.com/p/helvella-scheduling-blood-draws.html

The issue of how to time blood draws in relation to taking thyroid hormones is one the one hand largely ignored (by the medical establishment) but clearly an issue (from patients).

Timing most certainly affects results. And can cause inappropriate decisions about treatment including dose adjustments.

The best bit is the link to Tania's article at Thyroid Patients Canada. As so often!

Medicines Document - Divide and Conquer

After much consideration, and vacillation, I have made a momentous decision regarding my medicines documents.

The document started as a simple list of the UK products with few details. Largely because I was sick of posting that list on the forum. But also because when it is posted in a HealthUnlocked post, it doesn't ever get updated. New products can arrive, and old ones disappear, but if a member falls across an old post, they could be seriously misled.

It would never have been brought into existence if the information had been readily available elsewhere. But all the main UK sources have problems:

British National Formulary doesn't say anything about the medicine itself. Not even the product names. The identification is by supplier - not manufacturer or formulation. And it tends to be out of date. (That has improved considerably over the past few years. I think they now have direct links to other sources.)

NHS Drug Tariff doesn't identify products. Just a simple statement of the reimbursement prices. Occasionally you can infer which product as in the case of liothyronine capsules - there is only one product!

The electronic Medicines Compendium (eMC) is incomplete. Teva levothyroxine has never been included. And Accord levothyroxine, which used to be there, is no longer. 

The MHRA's document store is diabolical to access. A really unfriendly search facility. (Though many links in my document make use of it as it is the only up-to-date source of all UK documents).

Even were all these source good, they don't make clear issues like 'own-label suppliers'. Where a company other than the manufacturer/importer supplies a product under their own name. Examples have included Almus and Northstar.

Trouble was, even with that UK information collected in one document, it missed out on the rest of the world's medicines. Which was a serious issue for the ones which are frequently mentioned. Such as Abdi Ibrahim Tiromel, Grossman Cynomel and Thybon Henning.

So my document expanded, EU (and EEA) at first, plus known other products, and USA, Then the realisation that there is no publicly accessible list, in English, for much of the world. So it kept expanding and was limited only by accessibility of information - and my ability to understand. (Which is why China is almost entirely absent.)

It eventually reached over 600 pages. Unwieldy and simply too much.

Thus I have decided to split the document in two - UK, and Rest of the World.

UK will be more complete. It will have the matrixes of products.

RotW will be thinned out. Products available in multiple countries will largely be separated out to reduce duplication. (But, where possible, there will still be basic details and links to documentation like Patient Information Leaflets, in each country.)

If you only care about the UK, it will be much slimmed down. If you care about RotW, it will be simplified and much easier to see the same product supplied to multiple countries. Sometimes these are not clear - quite often being sold under different company and brand names. With the confusion that there are near-identical company names which are entirely unrelated. Same brand names are used for different products - occasionally even within a single country. And apparently identical products - same company, same brand, but different formulations.

Find out more, including links to the actual documents, here:

https://helvella.blogspot.com/p/helvella-thyroid-hormone-medicines.html

If you find anything incorrect, misleading, typos, links that don’t work, etc., please let me know. Go to my profile and use the contact details there:

https://www.blogger.com/profile/17095075774834042563

 

NHS Codes for Tests

 I've just added a page which might help decipher the codes we see alongside test requests and results within the NHS system.

 

https://helvella.blogspot.com/p/helvella-codes-for-tests.html

What can you find here?

 So far, my blog has the pages of information listed below. Many link onward to PDFs (or other formats) available on Dropbox or Google Drive.

For the larger documents, it is recommended that you download the whole document in order that the Tables of Contents and links work properly.

For spreadsheets, if you open them in Google Drive, you should be able to use them online without needing any spreadsheet software on your device.

There is no need for registration, nor is there any cost. Nor do I add any advertising or tracking. (Sorry, but as this is a Google hosted site, they do what they do.)

• helvella - Animal Thyroid in The British Pharmaceutical Codex of 1907
• helvella - Editing HealthUnlocked Posts/Replies
• helvella - Estimation of Levothyroxine Dosing in Adults
• helvella - Historical Context of Thyroid Treatment in the UK
• helvella - History of Thyroid Hormone Medicines in the UK
• helvella - Historical Prices of Liothyronine Tablets in the UK
• helvella - Iodine Patch Test
• helvella - Jostel Index Calculator
• helvella - Levothyroxine Brands History
• helvella - Links and References
• helvella - Selenium Document
• helvella - The End of Thyroid BP
• helvella - Thyroid Hormone Medicines
• helvella - Vade Mecum for Thyroid

Abbreviations and Acronyms

Active Pharmaceutical Ingredients (API)

International Non-proprietary Names (INN)

British Approved Name (BAN)

Alerts for Medicine Recalls and Warnings

Amino Acids Anaemia

Anatomical Therapeutic Chemical (ATC) codes

Antibodies Anti-Thyroid Therapy

Autoimmune Thyroid Disease (AITD)

Calculators and Convertors

Daily Rhythms of Thyroid Hormones

Data Matrix Codes

Deiodinase Enzymes (DIO1, DIO2 and DIO3)

Desiccated Thyroid and Thyroid Glandulars

Desiccated Thyroid Ratios

Digital Object Identifier (DOI) Links

Dimensions of Capsules

Donating Blood

Elements

EU Falsified Medicines Directive

Excipients Expiry Dates

Famous People with Thyroid Disease

Fine Dose Adjustment Genetic Polymorphisms

Gluten-Free Status of Medicines (UK)

Graves’ Disease

History of Thyroid Treatment and Medicines

Hydration: Anhydrous vs. Pentahydrate

Human Hormones Hypodermic Needle Sizes

Hypothyroidism Symptom List

Iodine Content of Thyroid Hormones

Iodine Patch Test 

Iron

Levothyroxine Advice

Medicine Classifications 

Medicine Documents 

NHS Drug Tariffs

NHS England Integrated Care Systems (ICS)

NHS Scotland Health Boards.

NHS Wales Health Boards

Pathology Handbooks

Patient Records Access

Pharma Contacts

Pharmacies Online

Pharmacy Locations

Prescribing by Brand

Prescribing Levothyroxine by Brand

Prescription Charges

Prescription Latin

Pretibial myxoedema

Ranges and Reference Intervals

Serious Shortage Protocols Shortages

Test Interference by Biotin Tests (Summary)

Tests – LabTestsOnline

Thyroglobulin (TG)

Thyroid Binding Proteins

Thyroid BP – The End

Thyroid Cancer

Thyroid Diseases, Disorders and Syndromes

Thyroid Eye Disease (TED) 

Thyroid Hormone(s) 

Thyroid Hormone Medicines 

Thyroid Hormone Ratios 

Thyroid Peroxidase

Thyroid Stimulating Hormone

Thyrotropin-releasing hormone (TRH)

Thyroxine (Levothyroxine, T4)

TSH Receptor Antibodies (TRab)

Units – Grams, Milligrams and Micrograms

Vitamin B6

Vitamin B7 (Biotin)

Vitamin B9 (Folate/Folic acid)

Vitamin B12 (Cobalamin) 

Vitamins

X-codes

Yellow Card Reports

• helvella - 28-day Prescribing
• A PDF Conversion of Dr Lowe’s Thyroid Science Website
• Beware the Salchichon!
• Current NHS Drug Tariff Liothyronine Prices
• Dr. E. HERTOGHE on Chronic Benign Hypothyroidism
• NICE Guidelines are NOT mandatory
• Norfolk & Waveney CCG T3 Costs
• Papers by diogenes, et al.
• Prescribing of Liothyronine (RMOC Guidance - 2019)
• Skin Issues and DermNetNZ
• Solving the hypothyroidism puzzle
• Tattybogle - List of References recommending GPs keep TSH lower
• The First Treatment of Myxoedema in County Londonderry
• THE LIFE-HISTORY OF THE FIRST CASE OF  MYXOEDEMA TREATED BY THYROID EXTRACT
• The normal range: it is not normal and it is not a range
• Thyroid S Batches

If you find anything incorrect, misleading, typos, links that don’t work, etc., please let me know. Go to my profile and use the contact details there:

https://www.blogger.com/profile/17095075774834042563