Sister's Blue Horizon Thyroid Genetic Panel test results in. Great brains out there please help.

[MacG]

My sister has just received her results from the Blue Horizon Thyroid Genetic Panel test. They use a traffic light system when giving the feedback and two of my sisters results are flagged up as red “a potentially negative impact” either due to both variants being present or a “wild type” result that is “not as beneficial as the variant”.

Bit of context: my sister was finally diagnosed as hypothyroid in November last year and is currently on a trial of 50mcg Levothyroxine daily. She has her first appointment with an endocrinologist on Feb.28th (I am going along to that appointment with her). What do I want from this post? I want to try and get my head round the implications of these genetic results before that appointment as I am keen to try and help my sister move forward. It is a complex picture: Type 1 diabetes since she was a teenager and started with seizures (diagnosed with epilepsy) in her early 50s. In addition, for about the last decade she has suffered a lot with pain and has been told she has fibromyalgia. Pain, brain fog and fatigue (I’m thinking thyroid) are what severely impact on her quality of life day-to-day. My sister is in a dreadful state (now has carers two or three mornings a week). I fear that she has been consigned to the scrap heap, a half-hearted reactive approach to management of symptoms rather than a proactive approach to root causes. Hence my desire to try and get my head around things a bit so that I can try and support her as best as possible.

Great brains out there please help!!

The two genetic issues signalled as red are as follows:

1) Gene code: PDE8B Gene Function: TSH Signalling

Details given on gene function: “PDE8B is found in the thyroid but not the pituitary, and is involved in TSH signalling. It is thought that the variant decreases the response of the thyroid gland to TSH stimulation.”

The Impact and advice given is as follows: “You may be susceptible to reduced thyroid sensitivity to TSH stimulation which could result in a need for and production of higher TSH levels in order to produce normal levels of thyroid hormones (T4 and T3).”

2) Gene code: TRHR Gene Function: Thyrotropin Releasing Hormone (TRH) Receptor

Details of gene function: “Responsible for the body’s receptivity to TRH which stimulates the secretion of TSH from the pituitary gland. In turn, TSH stimulates the production of thyroid hormones from the thyroid gland. TRH is an important part of the negative feedback loop that ultimately regulates thyroid hormone levels. Variants have been shown to affect TSH levels.”

Impact and Advice: The “G” result [my sister’s result is showing as two “G”s] has been associated with a less responsive NEGATIVE feedback mechanism. Carriers of this genotype may show higher circulating TSH:T3/T4 ratio due to delayed reduction of TRH and TSH in the presence of healthy thyroid hormone levels. This may mean that the body is subject to less efficient response to changing thyroid hormone requirements.”

I am not at all from a scientific/mathematical background, so feel a bit nervous in putting out what follows, which is me paraphrasing the above information to check whether I have understood it and every so often I will throw in a question, which I will clearly signal.

I am going to start with the second of the two genetic issues the TRHR issue.

OK, I think I understand that because of the delayed reduction of TRH/TSH in the presence of healthy thyroid hormone levels in the blood (i.e.,“circulating levels”, recognise that this is not showing what is going on at cellular level) your pituitary is still pumping out TSH. Ques: In this case will your blood test results tend to have a relatively high TSH even though your T3/T4 levels may be showing as OK. (i.e., is this what it means when it says “higher circulating TSH:T3/T4 ratio”)? In addition, there is also the effect of the first genetic issue mentioned above (PDE8B) the reduced thyroid sensitivity to TSH stimulation. Presumably, given this first genetic issue (reduced sensitivity to TSH stimulation), it is desirable that because of the second genetic issue (delayed negative feedback loop) her pituitary IS pumping out so much TSH. So, do they cancel each other out??? Sorry if all this seems really basic. AND do these two genetic issues tend to come together like this?

But, wondering how this plays out in how my sister is able to function on a daily basis. Am I right in saying that throughout the day, if everything is functioning as it should be, your body is making finely-tuned adjustments to how much thyroid hormone you need. Example: Your body perceives a need for more thyroid hormone if you are climbing a mountain in cold weather conditions as opposed to when you are at repose in a nice warm bed??? This “clunky” negative feedback loop along with reduced sensitivity must mean that there are periods of time where my sister has either too much or too little thyroid hormone for the job in hand?

Any help would be MUCH appreciated. I am up for reading academic articles.

A final thought: I think that this genetic profiling is the way forward in medicine, but unfortunately given that a contingent (…and a significant contingent) of health professionals will not engage with any of the private testing, nor indeed symptoms, and persist in testing TSH only, how are we ever to move forward?

[Marz]

It would be good if jimh111 and diogenes could comment.

Good your sister has you keeping an eye ....

[MacG in reply to Marz]

Thank you Marz

[diogenes Remembering]

This situation is extremely complex involving as it does two thyroid associated genetic problems. The PDE8B one is found in the thyroid. A substance called cyclic AMP is a kind of messenger to help T4 and T3 production in the thyroid in response to TSH stimulation by the pituitary gland. Ths mutation reduces the amount of cAMP so that the thyroid cannot respond as well to TSH. Thus since T4 and T3 production is hindered, more TSH will be produced by the pituitary to try to force the thyroid to make more. This results in your thyroid parameters probably being quite different from the normal, and this must be taken into account when treating. The other mutation also doesn't help. This is a highly specialist field and needs really expert help. Unfortunately, and I have to say this, the mutation has longterm implications for health.

[MacG]

Thank you so much for responding Diogenes. I can follow and appreciate what you are saying. Before I saw your reply I was just chatting on the phone to my sister. I think we are both realistic about long-term outcomes, especially given the wider picture with her health issues, but are hoping to achieve some improvement. It's who to turn to in this highly specialist field for that expert help??

[helvella Administrator in reply to MacG]

If you click on the blue Reply (rather than in the Reply to MacG box), diogenes will get alerted.

Or, as I am doing, type @diogenes diogenes and select the name from the list you are shown.

[MacG in reply to helvella]

Thanks Helvella, it has just changed a bit since I was last online.

[diogenes Remembering in reply to MacG]

Perhaps enquire at Addenbrookes in Cambridge. They have thyroid specialists and if you put your case, might be able to help or at least point you to someone sufficiently specialised.

[MacG in reply to diogenes]

Many thanks for your suggestion. Much appreciated.

[jimh111]

Sorry, about to go on a long flight Home so wil be out of touch physically and mentally for a few days. Will try and revisit then.

[MacG in reply to jimh111]

Thank you, I'll keep an eye out. Hope you have a good journey.

[AmandaK]

Hi MacG, I came across your posting when searching for genetic testing on the site. I sent a private message and I'm not sure if you have received it. Hope to hear from you soon. Thank you