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Wednesday 31 May 2023

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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Monday 8 May 2023

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.

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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:

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