Jussi from Finland - Dx 2008 - 30.3.1991 - 23.8.2019 R.I.P.

[arojussi]

Yes that is exacly how it works as far as I know. my tyrosin level is still normal, so I can think about this in peace. Goal with tyrosin treatment is usually to have tsh to higher end of normal range. Tsh is more sensitive than t4v.

[D.ap]

Jussi ,

I believe your dx’d to be termed ,subclinical mild hypothyroidism ?
Until the T4 levels go down , then that would be called hypothyroidism ?

[Olga]

Jussi - the current understanding re. thyroid function and TKI treatment is that the TKI treatment success is associated with the low thyroid function, it is unclear if this is a causative or associative link - but I have seen many cases when people are intentionally trying to keep their thyroid levels at the low normal in attempt to control the growth of their tumors. I have posted an article before somewhere that it was recently discovered that there might be mode of growth stimulation independent from PD-L/PD-L1 that based on thyroid hormone stimulation of growth. Since your attempt with PD block was not successful you might actually have this second thyroid dependent variant of stimulation (although Keytruda nor working might be by whole bunch of reasons incl. antibiotics as you said or you being on continuous steroids treatment for the brain mets swelling at the time of Keytruda if I remember correctly - steroids are immune supressive so even if you unleash the immune system there is nothing to unleash...). May be do not rush with the thyroid supplements just yet or try to keep it on a low normal?
Also re. internal clocks reset - have you tried Melatonin suppl.?

[D.ap]

Josh used melatonin as well
Jussi and Olga here’s the link to tki and low thyroid benefits

http://www.cureasps.org/forum/viewtopic ... dism#p2621

[D.ap]

Medscape has an article as well
Here’s another article with the medscape login-

https://www.healthglu.com/news/hypothyr ... -survival/

[arojussi]

So looks like I wait with tyrosine medication for now. My t4v value inst even near the lower end of normal range and I don't have any new symptoms. So we wait until I develop symptoms or blood tyrosin level starts to drop.

I didn't use steroids when I started keytruda. I had first infusion 3 weeks after radiation and I lowered my dose to nothing in 3 weeks. Patient who need high dose steroids for immunotherpy related side-effects respond at least as well as patients who dont use any steroids.

[Olga]

Jussi - so you had the steroids during 3 weeks before you started Keytruda, right? Hard to say how active your immune system was then.
Re. patients who had steroids for the immune related adverse effect responding the same well as the ones that did not have to have steroids - they first get the immune related adverse effect which means their immune system gets to be highly active for awhile and only after that the steroid treatment is initiated - may be the tumor specific memory is already formed in the pre-steroids period (i.e. to have steroids and the immunotherapy after might be not the same as to have immunotherapy for awhile and steroids after)? There are lots of discussions lately about the need to tamper steroids rather fast when on the immunotherapy drugs treatment.

[arojussi]

With common sense the idea that immunosupressive steroids would effect in immunotherapy makes perfect sense. But I haven't seen study that would prove that. However there is clear evidence that antibiotics before or during immunotherapy start eliminates benefits. Most likely because keytruda need to interact with gut microbes.

Also my asps only has one mutation, so my immune system has hard time to recognize my cancer as foreign. This is great news actually. If my asps starts growing fast or in unusual places indicating that it has higher mutational load, I see no reason why I couldn't try immunotherapy again.

[arojussi]

Back to the problem at hand. I red studies and looks like in sub-clinical hypothyroidism there is consensus, that tyrosine medicine should be started once tsh is above 20 in repeated tests. With lower values benefits aren't so clear. Of course this was in general population not with cancer patients. Luckily my doctor is aware of better prognosis of hypothyroidism with tki treatment. At the moment plan is to start 25 micrograms of tyrosine tomorrow and see what happens. Another blood test is very unlikely to bring new information at this point.

[arojussi]

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2664572/

Subclinical Hypothyroidism: An Update for Primary Care Physicians

studtythat made me change my mind. Also at this point I trust doctor Kononen. Otherwise I would just have another lab test, that would most likely show same results as 2 earlier ones.

[D.ap]

Jussi
Have you had a scan of your neck / thyroid area lately?
Just saying it could be a possiblity of a tumor causing thyroid issues .

[arojussi]

https://academic.oup.com/jcem/article/8 ... 85/2848862

Subclinical Hypothyroidism Is Mild Thyroid Failure and Should be Treated

I think this article mentions increased lactate levels during exercise with hypothyroidism. Of course it is impossible to say what that means for asps patient in real life, but it might support tyrosine treatment.

[D.ap]

Jussi

I believe the biggest fear of doctors is that patients may become so lethargic and low thyroid that they have organ failure? I’m not sure when and how that is determined ..
Other than through symptoms and blood work .

Our oncologist has read of PD immune therapy patients being allowed to go upto the 200 levels before administering levoxyl .

[arojussi]

I had my whole body and brains scanned little over a week ago and hypothyroidism is common with tki, so microscopic met is possible, but extremely unlikely.

[D.ap]

Ultrasound can view thyroid .

Also , how are your calcium levels ? Parathyroid plays a role in hypothyroidism as well.