Does anyone have hypothyroidism induced by the immunotherapy drug Pembrolizumab?
If so are you having any trouble getting your TSH and T4 levels into the normal range?
My TSH was 66.88 in January. Early May it was down to 17.75 but has leapt up again to 29.86 and I can’t figure out why?
Anyone got any experience or suggestions?
Thanks
In terms of getting your thyroid replacement right, I'm guessing the only results you've got are TSH? A full thyroid panel consists of TSH, freeT4 and freeT3. You really need to see all three to get a full sense of what's going on.
Best practice in adjusting dose is to have a blood test every 6 months. Use the results to adjust Levothyroxine dose by 25mcg, keep dose stable for 6 weeks, then test and adjust again. Usually on the NHS we are kept waiting a bit longer than 6 weeks, but you want this rough pattern.
If you're being dosed on TSH alone, which is pretty inadequate, you should have had a 25mcg increase with each of those TSHs. They're pretty high, and with full treatment the TSH will need to be below 1, probably at the very bottom of the range.
TSH stands for thyroid stimulating hormone. This is a chemical message produced by the pituitary to stimulate the thyroid to produce more hormone. When the thyroid hormone in the body is too low, TSH will be high to show the body needs more.
This is how things work if all is working well. Unfortunately it's possible for this to go wrong in a few ways, and we end up with a TSH that doesn't match our hormone levels. This is why it's important to see the full panel.
You don't mention if you're feeling very unwell? I was pretty much struck in bed with a TSH over 60. If your symptoms don't match the numbers and you feel quite well, you definitely want to do a bit more digging and confirm that your thyroid panel matches up.
I am getting blood tests done every three weeks or so. I mark the blood work docket myself and no one challenges me. Unfortunately the hospital only test for TSH & T4. I know this is inadequate and have tried to discuss this with the endocrinology consultant...along with dietary considerations, drug interactions and vitamin deficiencies but she asserts that these things have no influence on the absorption of the Levothyroxine and that I shouldn't take any notice of any of the information and advice available on Thyroid UK website because they are not validated!
Essentially I started off on 25mg Levothyroxine at the beginning of January and increased the dose by 25 mg every 7-10 days (it was important I get the TSH level down quickly). However I hit a wall on the second day of taking 75mg...I was rattling around, agitated and speeding out of control. Raging and aggressive...I dared not leave the house or encounter another human being. I immediately dropped the dose back to 50mg and maintained it till about 10 days ago. I didn't have another appointment with the endo till early June and only then became aware that my TSH level had risen from 17.80 (15/04/2019) to 19.96 (06/05/2019).
To avoid a repeat of the aggression flare up I started increasing the dose by 12.5mg...now at 75mg again and experiencing hot flushes at regular intervals through the afternoon and evening and some mild anxiety symptoms. Last blood test on 24/05/2019 came back with TSH 29.64 and T4 10.3 but I really don't feel well, if anything I feel worse than I did when TSH was 66.88 (January)...then I was in the grip of outrageous insomnia that had been going on for over three months...awake for up to five days then sleeping for one night. I was a wreck but thought it was entirely a Pembrolizumab side effect even though the Oncologist denied it.
Last few nights I have literally dosed off for a few minutes and then been unable to get back to sleep till after 6.00am. I lie in bed trying but have a series of brain zaps every few seconds (feels like someone is using a stun gun inside my head)...they carry on and every time I get anywhere near dosing off they happen and literally jolt my head off the pillow. These are followed by hours of semi conscious hallucinations and paralysed nightmares.
Daytime I am disconnected and lethargic. Getting so much paresthesia around my lower rib cage, breasts, back and numbness and tingling in my arms and legs. Itchy rash on scalp, down back of neck and general itching on back...
Can't be sure if all of this is related to the hypothyroid or the Pembrolizumab.
I know what you are going to say but...
GP is completely useless. I changed GP in January because the previous one had consistently made such a mess of everything...thought I would start fresh and build a new relationship with a GP who would engage with my current situation but she sits in front of a turned off computer looking like a scared rabbit in the headlights...I have seen her about four times since the end of January and she always ends up saying she doesn't want to do anything till she has heard from my cancer care centre.
Cancer centre...I have reported (as advised in the Pembrolizumab literature) all side effects and symptoms to the oncologist and have been doing so since Sept 18'...to begin with they were misdiagnosing stuff or saying they hadn't heard of that (whichever) side effect. Then things got very serious and I had a bad couple of days and nights where my brain and whole spine felt inflamed...their response was appalling. Ordering an urgent MRI Scan middle of January which actually didn't take place until middle of March...long after the inflammation had gone down. They discovered beginning of January that my TSH levels had rocketed and in a hushed side remark said that I should have been having them monitored since the start of my treatment in July 2018 but they had been missed off the blood tests.
I have had to do loads of research about possible causes for the symptoms...Possibilities are; Autoimmune Thyroiditis, Autoimmune MS, Para-neoplastic Syndrome or the cancer. I am repeatedly going back to the oncologist (appointments at least three weeks apart and limited appointment time) but can't get any straight answers and no commitment about carrying out more specific tests to pin down (and hopefully treat) the cause. She says that she doesn't think its caused by the cancer...my tumours have shrunk consistently since treatment began and are now approximately 70% smaller.
Yet to catch up with the Endocrinologist but don't hold out much hope for any advice and support from her either.
So this brings me here hoping to find someone who has a like experience with Pembrolizumab and thyroiditus .
Long and complicated I know but the experts refuse to discuss what us mere mortals are good at sharing.
Thanks for your response.
Hi Llanigirl, sounds like you have really been through the mill! Suddenly becoming hypothyroid is also very unpleasant, so that just adds to everything else you've been going through 
Are you saying that your thyroid is being monitored and treated entirely by your GP? You're not getting any specific support for managing it alongside all your other treatments?
I think the best you can do in that case is ask to be treated along the lines of thyroid treatment best practice, which is to have your dose adjusted by 25mcg every 6 weeks.
Sounds like at one point you were trying to increase every week? I think that is a bad idea, because it takes the body quite a while to get used to thyroid hormone and settle down on a given dose.
And after that you suffered from not begin able to increase anymore with bad symptoms? This is quite common with thyroid hormone, and unfortunately the more sick we are the more likely it can be. Its said to be due to the adrenal glands struggling to keep up as the metabolism increases. You can support the adrenals by taking care of yourself, eating and sleeping well, making sure your vitsmins are optimal, and reducing stress. Unfortunately you're in a stressful situation, so all you can do is rest and be kind to yourself. Though its worth making sure vitamin levels are good, particularly ferritin, folate, vit D and vit B12.
The other thing you can do is increase super slow. Levothyroxine is slow acting, so it roughly averages out your weekly dose, which is useful for getting a slow increase. You could try eg increasing by 25mcg per week, for example having 75mcg on a Sunday, then 50mcg for the rest of the week. Keep that up for a week or so and then add in another day of 75mcg. You can go as fast as your own body can tolerate, so if you tolerate an increase of 12.5 per day, then that's even better.
If you keep the increase as a whole to a total of 25mcg over 6 weeks, you should be fine (eg increase the 12.5 now, then you can do 12.5 again in 3 weeks if you tolerate it). Just be aware that blood tests are only reliable if you've been on a stable dose for 6 weeks.
The goal is to get your thyroid hormone up, however you manage to fudge it. This will help every part of your body recover, because thyroid hormone is needed by every cell and organ in the body.
Did you say that you have some freeT4 results, too? If you do please share them, because the freeT4 helps to confirm where you are.
With thyroid hormone everything moves slowly, and it can easily take 6 months to get to your optimal dose.
Last results on 24th May were:
TSH 29.64
T4 10.3
Llanigirl, that TSH is very high. Do you have the range for that freeT4? Is it something like 12-22?
It could be extremely low. When taking Levothyroxine only, most people will need the freeT4 at the top of the range or even over to feel well.
Its likely you are very very undermedicated. All you can do is try to raise it however you're able to. Its a tough situation, because being this low puts a strain on your whole body and makes you less able to recover from other illnesses.
How are you and what are your symptoms? Can you take your pulse and temperature? The TSh is a largely unreliable test and can jump around a bit.
I regularly take my temperature, BP and PulseOx. All stable for the most part.
I know I need a wider range of thyroid blood tests but even with pushing the GP doesn't accept this and the Endocrinologist flatly denies it. Been a bit of a struggle as I am just trying to get my head around understanding it all and knowing what to ask for and challenge is difficult if your not fluent in your argument.
I am getting blood tests done every three weeks or so. I mark the blood work docket myself and no one challenges me. Unfortunately the hospital only test for TSH & T4. I know this is inadequate and have tried to discuss this with the endocrinology consultant...along with dietary considerations, drug interactions and vitamin deficiencies but she asserts that these things have no influence on the absorption of the Levothyroxine and that I shouldn't take any notice of any of the information and advice available on Thyroid UK website because they are not validated!
Essentially I started off on 25mg Levothyroxine at the beginning of January and increased the dose by 25 mg every 7-10 days (it was important I get the TSH level down quickly). However I hit a wall on the second day of taking 75mg...I was rattling around, agitated and speeding out of control. Raging and aggressive...I dared not leave the house or encounter another human being. I immediately dropped the dose back to 50mg and maintained it till about 10 days ago. I didn't have another appointment with the endo till early June and only then became aware that my TSH level had risen from 17.80 (15/04/2019) to 19.96 (06/05/2019).
To avoid a repeat of the aggression flare up I started increasing the dose by 12.5mg...now at 75mg again and experiencing hot flushes at regular intervals through the afternoon and evening and some mild anxiety symptoms. Last blood test on 24/05/2019 came back with TSH 29.64 and T4 10.3 but I really don't feel well, if anything I feel worse than I did when TSH was 66.88 (January)...then I was in the grip of outrageous insomnia that had been going on for over three months...awake for up to five days then sleeping for one night. I was a wreck but thought it was entirely a Pembrolizumab side effect even though the Oncologist denied it.
Last few nights I have literally dosed off for a few minutes and then been unable to get back to sleep till after 6.00am. I lie in bed trying but have a series of brain zaps every few seconds (feels like someone is using a stun gun inside my head)...they carry on and every time I get anywhere near dosing off they happen and literally jolt my head off the pillow. These are followed by hours of semi conscious hallucinations and paralysed nightmares.
Daytime I am disconnected and lethargic. Getting so much paresthesia around my lower rib cage, breasts, back and numbness and tingling in my arms and legs. Itchy rash on scalp, down back of neck and general itching on back...
Can't be sure if all of this is related to the hypothyroid or the Pembrolizumab.
I know what you are going to say but...
GP is completely useless. I changed GP in January because the previous one had consistently made such a mess of everything...thought I would start fresh and build a new relationship with a GP who would engage with my current situation but she sits in front of a turned off computer looking like a scared rabbit in the headlights...I have seen her about four times since the end of January and she always ends up saying she doesn't want to do anything till she has heard from my cancer care centre.
Cancer centre...I have reported (as advised in the Pembrolizumab literature) all side effects and symptoms to the oncologist and have been doing so since Sept 18'...to begin with they were misdiagnosing stuff or saying they hadn't heard of that (whichever) side effect. Then things got very serious and I had a bad couple of days and nights where my brain and whole spine felt inflamed...their response was appalling. Ordering an urgent MRI Scan middle of January which actually didn't take place until middle of March...long after the inflammation had gone down. They discovered beginning of January that my TSH levels had rocketed and in a hushed side remark said that I should have been having them monitored since the start of my treatment in July 2018 but they had been missed off the blood tests.
I have had to do loads of research about possible causes for the symptoms...Possibilities are; Autoimmune Thyroiditis, Autoimmune MS, Para-neoplastic Syndrome or the cancer. I am repeatedly going back to the oncologist (appointments at least three weeks apart and limited appointment time) but can't get any straight answers and no commitment about carrying out more specific tests to pin down (and hopefully treat) the cause. She says that she doesn't think its caused by the cancer...my tumours have shrunk consistently since treatment began and are now approximately 70% smaller.
Yet to catch up with the Endocrinologist but don't hold out much hope for any advice and support from her either.
So this brings me here hoping to find someone who has a like experience with Pembrolizumab and thyroiditus .
Long and complicated I know but the experts refuse to discuss what us mere mortals are good at sharing.
Hypothyroidism is one of the top autoimmune side effects of Pembrolizumab treatment. Pembrolizumab does not target leukocytes and antibodies... it pushes the immune system into overdrive and boosts T cell production enabling your own immune system to recognise and fight the cancer...unfortunately it also causes your immune system to attack your body causing a number of autoimmune diseases.
Well done for ordering you own NHS bloods.I might get into the habit of taking a pen with me to GP surgery for the same purpose although I think they are done on computer.I dont know that we are going to get to the cause of your TSh rising up as it has. The thyroid is a very sensitive organ I think to toxins it might well have been this chemotherapy. If you specialist should have been monitoring you thyroid maybe one if the cancer charitys with a helpline might be able to advise.
In terms of your treatment your levo should only be increased every 6 to 8 weeks, things have to be done very slowly with thyroid hormones. You need you bloods done every six weeks or so and need to include folate, ferritin, vitamin D and B12.
We are validated and recommended by the NHS and I am also sure there is information on the British thyroid association website re the need for the vitamin and minerals we recommend. Maybe you would like to print your endo off some of their info if she is not impressed with TUK. I have heard about these electric shocks to the head before. Are you also getting muscles twitching? Can I suggest you get some magnesium citrate to drink before you go to bed. I expect you are deficient anyway. You also might want to get some B12 patches or supplements.
Thanks for replying.
I did print off information from Thyroid UK...that is what prompted her criticism of them.
I am in a bind with the blood tests to some extent.
The hospital only test for TSH & T4...the Endocrinologist claims that nothing else is needed.
The GP, at my insistence and very reluctantly will test for antibodies, Vitamin D, Vitamin B12, Ferritin, Calcium and cholesterol. The GP is very difficult to access and I literally have a fight to get the results. They prefer to have a receptionist tell me 'they are fine' instead of just as a matter of standard practice give me a print out of the results. Took me nearly a week of phone calls and two visits to the surgery to get the last test print out and two days later I received a letter putting me on 12 months notice being de-registered with the practice for aggressive and abusive behaviour because I dared to inform receptionists that were blocking me (by claiming I could not have the print out because it breached data protection) of what my patient's rights were. Apparently they felt threatened and intimidated by my assertiveness.
I am doing the best I can to add Vitamins and supplements to my diet but have to run everything past the oncologist before I introduce it in case it contraindicated with the Pembrolizumab. In addition, I am totally new to all of this and simply don't have enough knowledge about it all.
Hi Llanigirl,
Pembrolizumab belongs to a group of immune therapies called PD-1 (programmed cell death 1) inhibitors. Cancer cells evade the immune system by shutting off this pathway, making it impossible for the immune system to recognise the tumour threat. The immune therapy blocks this pathway, so the immune system can 'see' the tumour and mobilises the immune system by activating T-cells and natural killer cells to deal with the invasion.
Thyroid disorders, mainly hypothyroidism, is a well recognised side effect of PD-1 therapy and it is believed that the activation and restoration of the T-cell function may be the cause of the development of thyroid dysfunction. In some patients, the hypothyroidism resolved, in others corrective treatment is needed.There is a paper which describes this in more detail, if you are interested:
ncbi.nlm.nih.gov/pmc/articl...
The summary of product characteristics of pembrolizumab states that hypothyroidism is a very common side effect of treatment. The recommendation is, that patients on PD-1 therapy should be closely monitored and tested for thyroid function from the start of the treatment and corrective treatment should be initiated if the patient develops symptoms.
Pembro side effects include things like rashes, itching and inflammatory side effects - as this is an effect of stimulating the immune system. Inflammation is well described and if the effect is severe, you should have been given steroid treatment to counteract the inflammatory effect. There are well documented trteatment pathways depending on the severity of the inflammation (grade 1, 2 etc - your oncologist should be well informed about that, as these medicines have been around for a while now, unless he is a real numptie!)
Effects like lethargy are definitely related to hypothyroidism, if you don't have enough free T4 and T3 to work with, you will be zapped of energy and your TSH is definitely far too high. You should have been given advice on how to safely increase your levo dose so the TSH can drop. Yes, things like Vitamins and minerals can help with conversion and making sure your body can use the medicine, but the high TSH indicates that you get far too low levels of thyroxine.
Like others have suggested, I would also try to increase the thyroxine, and see what feels right for you (not everyone can tolerate the fast increases - having said that you should try to increase it as fast as you can so your metabolism can start to work properly again and you will feel better. Yes, too fast increases can cause flushes and anxiety, but interestingly, anxiety and irregular heartbeats can also occur if you are severely under medicated!
Try to keep on top of your GP and insist that they look into this a bit more closely. A TSH like yours is severely out of range and since they bang on about these 'normal' ranges, tell them that they have a duty of care to sort yours!!
Thanks for your informative reply. I have already done a lot of reading about Pembrolizumab and I'm pretty aware of it's side effects both physically and theoretically.
I am being treated with Levothyroxine under the supervision of the Oncology Centre Endocrinologist. That said I have only seen her twice in the last six months and I am managing my own increase of dosage for the levothyroxine. They aren't much help to be honest. I was not aware of the increased doses being applied every six weeks and have been increasing more randomly than that. As for the testing I try to get it done every three weeks because the Pembrolizumab is constantly destroying the thyroid gland and sending TSH and T4 figures out of whack. I don't know whether it was just scare tactics but the Endocrinologist told me in January that I could go into a coma if I didn't take the levothyroxine. She didn't give me any information how high the TSH or how low the T4 would have to be before that became an imminent danger.
I have had a range of symptoms going on since the beginning of the year, including a period of about three days where I experienced inflammation of the brain and spinal cord that had me waking one morning with numbness in both legs. Despite calls to the Oncology centre 24 hour emergency helpline, 111 service, being taken to hospital by ambulance I received no medical assistance or treatment with this issue. Essentially and rather shockingly I found that one service played off against the others and I spent several days being rebounded around each, with each telling me the other would deal with the issue. The reality was that no one helped me.
I kicked off on the Oncologist over this and she finally (14 days later) ordered an urgent MRI scan at the end of January which didn't actually take place till middle of March...by which time the inflammation has subsided.
I can't get any answers from her about whether the symptoms are being caused by the cancer, para-neoplastic syndrome, hypothyroidism or some other (MS) autoimmune disease caused by the Pembrolizumab. She says that the MRI has not revealed any demyelinisation which would be present with MS but she isn't making any assertions about other causes and does not see the need for further investigations or tests. My point is that early diagnosis and treatment of side effects of Pembrolizumab is essential if full blown auto immune disease is to be avoided and given the situation I endured in mid January possibly life saving for me.
She did refer me to the pain management clinic where the consultant prescribed me Pregabalin without any hesitation. Needless to say I have enough problems without adding to them with that monster drug.
Without much support from the Oncologist or Endocrinologist I am at a loss and hoped someone online might have encountered similar problems with their immunotherapy treatment,
Llanigirl. I am reading your replys and am so shocked at the lack of care and consideration you are receiving from the services that are supposed to be helping you. I am hoping you have a close and kind family supporting you or some caring freinds. It seems to be all the services have become so target driven and tech monitored that they have lost all humanity. I wish I could send my big fluffy dog Hector to give you a cuddle and a bottle of wine or whiskey. Sleep well and dont let them get the better of you.
Well Mandyjane I am sure I would really enjoy meeting Hector. I don't actually drink but thank you for the offer.
I was shocked and not least a bit outraged to begin with but as I've gone along I am finding peoples experience quite often matches my own and disturbingly in many cases are grossly worse than my experience. There is a great variance in the effectiveness of services from area to area, trust to trust and disturbingly in some instances from department to department in the same establishment. I have many examples of some really ridiculous dysfunction from just my contact with the first hospital, GP and healthcare trust. Keep thinking I might write them up but not sure what I could do with them.
Complaining is not an option. They will just tie me up in red tape and it won't change anything. The system is broken.
I am dealing with all this single handed. Adult children, son 28 and daughter 31 just seem to want to keep it out of their lives...this became clear on the day that the diagnosis was delivered. They had by that point seen me stressing and spitting feathers about so many things that were wrong and continued to cause me distress. I was by that time, (after 18 weeks of misery and conflict) incredibly but understandably inflamed. All trust destroyed and on the offensive with everyone inside the health service I had to encounter and deal with. Meanwhile, responding as children do, they were both embarrassed by my stressed behaviour and not able to understand that the reasons for it were justified. Such ridiculous and frustrating things had happened.
After we left the first meeting with the oncologist we all went to a nearby pub for a meal, I thought we would discuss how we would deal with things and support each other as a family going forward, just as we always had but with both of them sitting across from me at the table it became clear that they had talked it over between themselves before we sat down and I found that they were presenting a unified policy...simply saying whatever I decided they would support me... before shutting the whole conversation down.
That was a year ago and I thought it would work out and we would find a balance but it hasn't...they don't want the stress of it or so it seems to me. They don't want to hear about any of it, shut me down - sometimes abruptly when I try to talk. Even to the point of having fits on me when I have been ill and asked for help - bringing round some milk and a few groceries led to my son leaving abruptly saying he didn't want to come round to my pity party when I tried to tell him what was going on with me (I thought he should know in case I had to go into hospital) and he may need to give doctors information if I was unable to.
Other stuff happens. My daughter is the cruellest. I'm not sure she means to be but that is the effect.
It's shocking, painful and disturbing to me in equal measures but I try not to think about it because the pain of that far outweighs anything else I am dealing with.
I have discovered that this is not uncommon. I have joined a Facebook group of people around the globe who are having Pembrolizumab treatment and several of those ladies are having similar experiences. Hard to fathom. I for one always put my children at the top of my list. No one and nothing took precedence over them. I am still there in a shot if they need me. Conscience wouldn't allow me to be any other way.
Dear Llanigirl,
There is nothing I can say and I have no advice to offer, but I am simply sending you a virtual hug across the pond. I’m glad you found a Facebook group where you can speak to folks going though what you are.
Wishing you all the best and sending you a prayer today that you will find some relief for your cancer and thyroid issues as well as your family ones. 🤗
Thank you
Hypothyroidism? 
Hypothyroidism?
Hypothyroid 
Subclinical hypothyroidism
Hypothyroidism? 
