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August 23, 2014 at 2:43 pm #22147
Many of you know my earlier history with Stage IV. A little repeat. 4 doses of IPI in late 2012. Glad to be alive and no certain recurrence for 16 months. But thyroid problems since at least last November. Diagnosis of Grave’s disease in January along with hypophysitis, though I have no idea how the latter would have been diagnosed without MRIs with a pituitary cutout. Radioactive iodine treatment for the Grave’s disease in March. Switch quickly to very low T4 and TSH readings to almost normal T4 to declining TSH (from 57 to 22 this week). Thyroid measurements then seem to be coming back to normal, but I am feeling much worse than I did in June. My primary care doctor believes it is something more than the thyroid that is giving me problems, but he can’t figure them out. Headaches in sinus region (may have had them in the course of or soon after ipi but I have allergies so didn’t think much of them since they are rarely intense), lethargy, weakness in legs, lack of equilibrium, fatigue, difficulty walking. Two months ago I was working out for competitive swimming a mile to a mile and a half on most days.
I have an endocrinologist with a fine professional reputation, but he has no background in ipi symptoms and did not seem too interested in reading anything on its possible relationship to the thyroid and pituitary symptoms and disease that he has diagnosed. Perhaps one does not need to know anything about ipi in order to treat pituitary and thyroid symptoms correctly. But his indifference to cause bugs me. I am concerned now after losing my thyroid function thanks to the iodine radiation that his Grave’s disease diagnosis might have been too hasty since Hashimoto’s also has hyperthyroid cycles. I’m seeing the endo again on Wednesday. I don’t want to be my own doctor, but I would be very much helped by any specific suggestions or information you might have, especially from you who have had thyroid and pituitary problems following ipi or other immune therapies Apparently similar situations can also arise with IL-2 Thanks, friends.
FrankAugust 23, 2014 at 6:57 pm #65241msue5Participant
Have you considered going to an immunologist? I was sent to one for my Lupus and he was the one who came up with a solution to my ongoing problems. My Rheumatologist referred me and I really respect any Dr who admits he needs a fresh perspective and is willing to admit it. They have a really intimate knowledge of any immune system disorders.
Mary SueAugust 25, 2014 at 2:26 am #65242BNP68Participant
I think your endocrinologist indifference would frustrate me as well. I consulted with a couple endocrinologist about my hypophysitis and with both of them I brought a copy of this paper. The first endocrinologist was already familiar with the paper which made me feel good and the second was happy to have the information.
BrianAugust 25, 2014 at 4:02 am #65243Celeste MorrisParticipant
So sorry that you are having to deal with one more thing. I don’t blame you for wishing your endo had more interest/knowledge about the possible connection to ipi! Endocrine problems are known to occur after its administration. Here is an article that confirms such…(though you pretty much know this already!!!)
Endocrine-related adverse events following ipilimumab in patients with advanced melanoma: a comprehensive retrospective review from a single institution. Ryder, Wolchok, et al. Edocr Relat Cancer. 2014 March 7. “Novel immune checkpoint blockade with [ipi], an antibody blocking the cytotoxic T-lymphocyte antigen 4 is revolutionizing cancer therapy. However, [ipi] induces symptomatic and sometimes severe, endocrine immune-related adverse events that are inconsistently recognized and reported.” In a retrospective study these folks looked at 256 records of patients receiving ipi in clinical trials between 2007 and 2013. They looked at their hormone related labs, X-ray results, and clinical histories. After ipi, they found that the patients demonstrated an 8% incidence of hypophysitis, 6% dealt with hypothyroidism/thyroiditis, and primary adrenal dysfunction was rare. When Nivo and ipi were given together, there was a 22% incidence of either thyroiditis or hypothyroidism, and a 9% incidence of hypophysitis. “Symptomatic relief, in particular, for hypophysitis, was achieved in all patients with hormone replacement, although endogenous hormone secretion was rarely recovered.” “Prompt initiation with hormone replacement reverses symptoms.”
Not sure how much that will help…but hang in there. I would certainly seek a doc with more interest and knowledge if at all possible. Can you return to, or contact, the doc who administered your ipi?
Wishing you my best, CelesteAugust 25, 2014 at 12:23 pm #65244AnonymousGuest
Frank, please see another endocrine specialists like right now or at least get your GP and/or oncologist involved and maybe a small dose of prednisone. Endocrine related problems from IPI can be delayed but need to be treated quickly. Your oncologist who gave you the IPI I’m sure would back me up on this.
JeffAugust 25, 2014 at 6:05 pm #65245
Thanks to all of you very much for your postings. I’ve already sent on references or somewhat digested copies of the two articles to my endocrinologist before my visit in Wednesday. Jeff, I think you make good points. I have written my oncologist but have not heard back from him yet. As for finding someone else, I will do so if this next consult is unsatisfactory. The first endocrinologist I saw did not recognize any value in reading up on ipi, which he considered unrelated, nor having contact with my oncologist. I broomed him immediately. I stuck with the current one because of his sterling credentials in the field (despite poor patient online reviews) and his location at the University of Michigan where I am being treated. But he also expressed skepticism at our first meeting about the possible relationship between my problem and ipi.I presented with a hyperthyroid condition and he only knew that there might be a connection if I were hypothyroid and during or immediately after the infusions I did not want to continue to keep looking for someone and talked myself into believing that he did not really have to explore the ipi connection to treat me properly for my disease(s).August 26, 2014 at 11:19 am #65246Catherine PooleKeymaster I think you originally had a consult at Sloan? Perhaps it is time to contact the folks there about this situation. I hope things get more clear soon.August 26, 2014 at 11:38 am #65247 Another good idea, Catherine. One I have been thinking about if I strike out again this week. Jed Wolchok (sp.?) was one of the authors in the recent study that referenced the relationship between ipi and pituitary and thyroid problems. I hope (?) that might have had an influence on Sloan’s practice in cases like mine.
FrankAugust 26, 2014 at 9:45 pm #65248KarenJParticipant
My husband’s pituitary was whacked by ipi. All of the hormones that the pituitary controls are low: thyroid, cortisol, testosterone, HGH… It is critical to address the cortisol problem. A biologic dose of 15 mg hydrocortisone in the morning and 5 mg at night is what he takes. When he is on dexamethasone, he doesn’t take the hydrocortisone. But you definitely need something to replace the cortisol if your pituitary has been affected. His mel doc said it is an uncommon but known effect of ipi. In some cases, the pituitary begins to function after several months, in some it doesn’t. I am surprised at your endocrinologist. FIND ANOTHER ONE!!! You don’t need someone who isn’t willing to learn something new in order to treat you!August 30, 2014 at 11:23 am #65249 Thanks all of you but Karen J and my oncologist are definitely on the same page. I was him yesterday, and he does feel I am suffering from a pituitary low cortisol problem. He put me back on hydrocortisone at 10 and 10 mg. a day. He is expecting that I will be feeling better quickly if this, indeed, is the problem. He’s a very thoughtful man, and he spent more than a few minutes of our appointment just thinking and making sure he looked over all my records including a close look at my brain MRIs because he still does not want to overlook possible metastasis to the brain again, which could also lead to similar symptoms. To be sure, I will have another brain MRI on Tuesday, though he is much more inclined to believe it is a pituitary problem. So I hope he is right, but I know if he is not, he will get to the bottom of the problem as quickly as possible and that my situations is a definite priority for him. Glad I drove the almost 4 hour round trip to see him and we did not try to handle things on the phone. I’ll see the endocrinologist a week from Monday. Decide then whether to broom him.September 9, 2014 at 11:20 pm #65250 I saw the endo yesterday, and I guess he broomed himself. He told me that my hormones were coming back to where they should be based on the numbers, and he saw no hormonal problems that would require his services, though he offered to see me again in 9 months. When I offered the symptoms I was experiencing he attributed their likely cause to the fact that I have been through a lot since being diagnosed with Stage IV melanoma two years ago including treatment and seizures and I was getting old. He wished me all the best. I have no endocrinological problems, and endocrinologists are brought in as the last resort when no one has a better idea. He obviously doesn’t. Not sure yet what my next step will be. Undoubtedly back to my oncologist for starters. There is still no certainty based on the latest brain MRI (a week ago Friday) whether I have a metastasis up there or a radiation effect.September 10, 2014 at 3:05 am #65251RJoeyBParticipant Frank,
You mention “radiation effect” in the brain. Have you had a prior brain met and if so when and how was it treated (surgery, radiation, both) and finally, did you spend any time on Decadron/dexamethasone before or after treatment?
I ask all of this because I’m experiencing similar symptoms to what you mentioned in your original post: “lethargy, weakness in legs, lack of equilibrium, fatigue, difficulty walking” (but no headaches or sinus issues). I had a craniotomy for a single 2.5-cm brain met in February 2013, a single session of a CyberKnife in March 2013, then a full four-dose course of ipi (which I tolerated well, no issues) from April-June 2013. Everything was stable and I was feeling great until this past June. Exercising every day, lost nearly 50 pounds, felt better than I had since before my diagnosis in 2010. After 15 months of “pristine” brain MRIs, my June scan showed something going on at the original brain met site, along with cerebral edema in the surrounding tissue. No way to differentiate new tumor activity from radiation effect on the MRI, so they started me on dexamethasone and I had a repeat MRI at six weeks at the end of July. Both the “enhancement” at the original site and the edema were reduced by about half from the June scan, which made it much more likely to be radiation effect than new tumor growth. So we started a standard taper schedule off the dexamethasone which I just finished last week. Primarily since starting the taper, the symptoms you mentioned have slowly come on and worsened, to the point where now I can barely get up and down the stairs, have an awful limp, am worn out, can’t exercise, and now feel worse than at any point since my diagnosis, including from any treatment. I had most of the other common side effects of the dexamethasone, too, “moon face”, irritability, acne, voracious appetite and weight gain (welcome back 25 of those 50 lost pounds), difficulty sleeping, and fatigue. Some of those have improved since finishing the taper last week, but not the more serious ones that you noted. I now refer to dexamethasone as “the demon pill”. What’s troubling is this could either be from the dexamethasone or a return of the radiation effect since starting to taper the dexamethasone. In the meantime, we’re trying not to jump to any conclusions until my next brain MRI in three weeks.
So not trying to steal your thread with my own issue, I promise, just trying to compare notes because what I’m dealing with sounds possibly similar to what’s happening with you, but perhaps with different timing.
JoeSeptember 10, 2014 at 10:21 am #65252
Two brain tumors were discovered in early October 2012 after removal of my initial lung tumor in July. The course taken was ipi beginning in late October and SRS for the two brain tumors in early December. During the course of ipi I had rash, itching, fatigue, and some diarrhea, but no severe effects. The SRS did not cause any side effects other than transient fatigue.
I continued that spring with frequent brain MRIs, more frequent than usual because of a follow up to a radiation clinical trial I was on. There were indicators found through these of a possible further tumor.
My first seizures occurred in May. No definitive cause, though the team was tending to feel that the findings in the MRIs were evidence of another metastasis. I went on dexamethasone at this time along with Keppra and was pleasantly “high,” maybe even a little manic in the coming months. My psychological “high” solidified in June when it was determined that I was not dealing with a metastasis but a radiation effect swelling in the brain. I was able to train for and competed in swimming in the National Senior Games in late July.
I stayed on the dexamethasone throughout the summer but had a much worse and even life-threatening run of seizures the last day of July and into early August, which led to a craniotomy at the end of the month. No metastasis but a build up of tissue, a radiation effect. After the operation, I was switched from dexamethasone to hydrocortisone, which was gradually reduced and finally eliminated in June this year. I have been on large doses of Keppra and Vimpat, anti-seizure medications, since the operation and had to have a burr hole procedure on my brain in November because of a bad fall I took September 2013, which resulted in subdural hematoma on both sides of my brain.
After this procedure I developed symptoms that were puzzling to my surgeon, and he attributed them to “all that I had been through.” It took two months before a trip to a neurologist who tested thyroid blood levels and discovered extreme hyperthyroidism that had been the cause of my symptoms. Grave’s disease. One day on propranolol and I felt much, much better though it has taken months of treatment including radioactive iodine to get back to an almost euthyroid condition.
It is impossible for me to sort out what could be the possible cause(s) of all this. Now I wish I had kept a more adequate record of the timing of my symptoms. I never thought that I would have to figure any of this out for myself and that my doctors would not be able to do so. The way I feel has shifted dramatically at times. I had been feeling better almost every day during May and June, which I attributed to the thyroid improvement. I went off cortisone in June. The bottom dropped out a few weeks later. Was it related? I didn’t think so at the time. Probably. When I was put back on cortisone at a double dose, 20 mg. a day two weeks ago, I felt quite a bit better within 24 hour, but not as good as I had in early June. The good news is that I returned to the swimming pool yesterday for the first time in over 2 months, and a half mile of laps taken slowly left me with enough endorphins that I felt for a few hours better than I have in a long time. I know my oncologist and surgeon think of my swimming as being my magic elixir so they will be glad to know I felt confident enough to start doing it again.
I hope my too lengthy post is of help to you, Joey, in sorting out your own concerns and what factors may be contributing to them. I am personally convinced that the original cause of a number of these problems was the emergence of auto-immune disorders consequent on ipi. But that certainly does not explain everything outlined above. Lots of factors at play and a changing landscape.
FrankSeptember 10, 2014 at 5:03 pm #65253RJoeyBParticipant
Your post was perfect and clarified a lot about your situation, thanks Frank. Great to hear you’re back in the pool, swimming again!
Our brain met situations have a lot of similarities, yours first occurred about 4 months before mine but with the earlier onset of the radiation effect, you’ve had much more of a rollercoaster ride over a longer term. As it was explained to me and what I found in my own reading is that radiation necrosis occurs in about 10-15% of those who receive SRS, with no way to predict who is at risk of developing it. Onset is typically 6-24 months following treatment; I was squarely in the middle at about 15 months and it sounds like you were on the earlier side. And of course, there is no way to differentiate it on MRI from new tumor activity and the symptoms are the same as with tumor itself.
We’ve both had ipi, SRS, and surgery, albeit in a different order, but with similar experiences with each. With SRS, I only needed a single session of CyberKnife with no side effects other than very transient fatigue, but later development of radiation necrosis. I was only on the dexamethasone for 2-3 weeks just before and after surgery, and stayed on the Keppra a little longer until I finished the SRS. With ipi, I had no significant side effects during treatment, other than some fatigue that was cumulative with each dose, along with some mild rash and itching. My blood work, every 6-12 weeks, has been normal since finishing ipi in June 2013 and until recently, I hadn’t had any of these other symptoms.
With the dexamethasone, it was initially more of a “mood enhancer” for me, too, bordering on what some might call manic, but I felt very in control of things. And when my July MRI showed a reduction in the swelling with the only intervention having been the dexamethasone, we were relieved to know it was radiation necrosis and not new tumor, but recognized that we weren’t out of the woods yet.
Before the June MRI, I had developed a limp, and suspected something might be up, so I wasn’t shocked that the scan showed something happening. After starting the dexamethasone, the limp didn’t improve or worsen significantly. After the July MRI (six weeks after the one in June), we started to taper the dexamethasone and for the first few weeks, the limp remained stable. Only over the past 3-4 weeks has it worsened, along with the weakness, atrophy, fatigue, and joint pain.
As I mentioned in my last post, we’re trying not to jump to any conclusions, but figure it’s either one of two things related in one way or another to the dexamethasone. Possibly since reducing and now eliminating the dexamethasone, the cerebral edema has again increased and the radiation necrosis hasn’t completely resolved. Or, many of these symptoms are also possibly being caused directly by the dexamethasone or discontinuation of it. My situation is further confused by the fact that my symptoms are much more pronounced on my left side. Since my brain tumor was on the right side near the left side motor control, the initial reaction would be that the cause of my current symptoms is continuing radiation effect in the brain. However, I’ve had bone mets, mostly left side, that have been treated with surgery and/or radiation. My left proximal humerus is now a 10″ titanium rod following a partial shoulder replacement in 2010 due to one of my first mets. It has limited strength and range of motion and always will (I call it my “T-Rex arm”), and as a result experienced a certain amount of atrophy, but has been stable for more than three years until this recent issue, where it’s now the worst it’s been since just after the surgery. My left femur and tibia have both been radiated and eventually had surgery just above and just below the knee. So all of that prior trauma makes any additional fatigue, weakness, pain, and atrophy more pronounced in those areas. My whole body feels fatigued, and my right limbs are weak, just not as noticeable when compared to my battle-worn left limbs. That puts us back at square one trying to determine what’s happening until I have the MRI at the end of the month.
Next step could be reintroduction of dexamethasone or another steroid (understanding that dexamethasone is the drug of choice for cerebral edema). A second craniotomy could be in the future, too, if the radiation necrosis is again progressing and/or not resolving. Ideally, my symptoms will resolve on their own as my body hopefully adjusts (and my adrenal glands start doing their job again) to the elimination of the dexamethasone. Beyond that is a bridge we’ll cross when we get there.
Now that I’ve managed my own long email, I wonder whether what we’re both dealing with (you longer than me) is steroid-related rather than ipi-related? How long after completing ipi were you diagnosed with Grave’s? Has your endocrinologist ever offered if perhaps the steroids have contributed? I never realized until now what powerful stuff dexamethasone is, but understand why they try to not keep patients on it longer than necessary (beyond the immuno-suppressive effect that all of us melanoma patients want to avoid).
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