Gadolinium Contrast Agent & The New FDA Warning
By Mark Moyad, MD
Article originally posted Spring 2018 on PAACT.org
BREAKING NEWS!!!
The NEW, THIRD EDITION OF “BEYOND HORMONE THERAPY” book by Mark A. Moyad, MD, MPH is now available. Ask your doctor or check with Amazon and other fun sources to get your copy today! Yeah! You will love it so much that you will carry it wherever you go, and I am not biased whatsoever!
GADOLINIUM CONTRAST AGENT AND THE NEW FDA WARNING; ISN’T THAT WHAT THEY USED WHEN I GOT MY MRI OF MY PROSTATE? WHAT THE ______ IS GOING ON HERE?! I THOUGHT THIS CONTRAST AGENT WAS SAFE…RIGHT?
(Reference: https://www.fda.gov/Drugs/DrugSafety/ucm589213.htm ; and Ariyani W, et al. Cerebellum 2017.)
BOTTOM LINE
In 2017 the FDA has placed a warning on gadolinium contrast agents commonly used for MRI and wants more research on which agents remain in the body and any short and long-term safety information on these things. In the meantime, it would be smart to look at the chart provided by the FDA (see below) to see which ones appear to be safer and less likely to stay in the body. It would be smart to get an update on the safety of these things whenever your doctor requests an MRI with contrast.
WHAT ELSE DO I NEED TO KNOW?
I think some healthcare professionals (not many, but some) like to believe that some things don’t come with a catch. However, they forget that eventually everything in life comes with a catch and it might take time to figure out what that catch is. For example, I remember in the old days some “experts” thought that selenium supplements in high doses would fight or even prevent prostate cancer. Then, after time and more extensive research, we realized they were W-R-O-N-G (always capitalize when trying to emphasize a point)! Then there were all those folks that suggested taking acid reflux drugs for many years was perfectly safe. W-R-O-N-G! Then there were all those folks that thought over the counter, antibacterial soaps work better than soap and water. W-R-O-N-G! Then there were all those folks that thought someone could make better french fries than McDonald’s. W-R-O-N-G! Anyway, I digress (also use exclamation points whenever possible-they make you seem important)!!!
Anyhow, back to this interesting story that doesn’t have an answer, but at least has a warning that patients and healthcare professionals need to know about now. This doesn’t mean the warning will end up being true, but it suggests, like anything in life, you need to use medical technology wisely - always giving a major analysis of the pros and cons.
There are many that believe MRI is safe for imaging, and for the most part it has been incredibly safe. In some cases contrast agents need to be put into the human body in order to get a better picture or reading. For the most part, contrast agents are incredibly necessary. One of the most utilized contrast agents is GADOLINIUM. The FDA came out at the end of 2017 and said that all (not some) gadolinium contrast agents used in MRI must now carry a warning about how they could be retained in the body and potentially cause kidney injury. Please see the link to the FDA website (https://www.fda.gov/Drugs/DrugSafety/ucm589213.htm) to see if the gadolinium agent you may receive in the future is more concerning than others. For example, the brand name Gadavist (gadobutrol) is often used for MRI screening of prostate cancer and active surveillance, and tends to use much lower levels of this agent in the body (a very good thing) compared to other agents. What the FDA wants is for healthcare professionals to consider using a gadolinium agent that is not retained or held in the body for longer periods. Here is an excerpt of the table from their website.
FDA-APPROVED GADOLINIUM-BASED CONTRAST AGENTS (GBCAS)
Note: The body retains less gadolinium when using agents that have what is known as a macrocyclic chemical structure (Dotarem, Gadavist, and ProHance get a thumbs up, as you can see from the FDA table above). So theoretically, these agents are less of a concern. Gadolinium agents that have what is known as a linear chemical structure have higher levels in the body after using them.
So, here is what I would do the next time someone said I needed a prostate MRI with contrast. I would inquire about which gadolinium contrast agent they would use on me and see if it is one of those identified by the FDA that appears safer (macrocyclic). If it was one of the concerning ones (linear), I would think twice, ask for alternatives, or possibly seek out another imaging facility. Oh Moyad, you are overreacting! Nope! Maybe so, but when Hippocrates was around he said it best: “First, do no harm with contrast agents.” Okay, he did not say that exactly but he might as well have meant it when he stated the following iconic line “First, do no harm.” First, do no harm, in my opinion, means knowing all the potential pros and cons of anything medically that is about to be done to you. It means physicians should always objectively educate as much as possible.
Is the concern real with gadolinium? We don’t know. However, there are some studies showing that some of these gadolinium contrast agents could be retained by the body, notably in the brain. Yikes! Still, things get into the brain all the time and don’t necessarily cause harm unless the concentration is high. For example, mercury from eating certain types of fish can get into the brain and is concerning when it reaches a certain level, but in many people, the brain can handle some of this stuff.
Thus far, it appears that gadolinium contrast agents have not been linked to anything truly concerning for those individuals with “NORMAL KIDNEY FUNCTION.” How do I know if I have normal kidney function besides the fact that I like to go number 1 whenever I have too much water or beer? This is determined by a series of tests, especially blood tests (BUN, creatinine, GFR, etc.). These things are tested by your doctor for a good reason, and this is part of the reason you also get a urinalysis. Several things or tests help the healthcare professional determine if your kidneys are functioning normally.
The FDA is now asking the manufacturers of gadolinium agents to conduct more human and laboratory studies to determine the safety of these agents. Thus far, the one real adverse effect noticed with gadolinium agents is in a small group of patients with pre-existing kidney failure. It is called “nephrogenic systemic fibrosis” (NSF). Recently, the FDA received some reports of other organs impacted even in those with normal kidney function, but the FDA doesn’t know if the contrast agents themselves were to blame or not, ergo (that is a big time word) the additional warning and request for more research. Interestingly, this new announcement by the FDA was released more than 2 years after the FDA said it was investigating reports of some issues associated with gadolinium contrast agents.
So, what is gadolinium exactly? That’s a great question. It’s a “heavy metal.” It can help healthcare professionals see internal organs, blood vessels, and other tissues more clearly on scans when injected into the body. Most of the gadolinium is eliminated by the kidneys (love those kidneys - the most underappreciated organ in the body next to the skin).
Now, get ready for a Moyad politically correct ending to this part of the column. Gadolinium is absolutely necessary in many cases to get an accurate MRI scan. And, if your kidney function is normal, there has been no direct link with these contrast agents to any specific health issues. BUT, and this is a big BUT, it’s up to you and your healthcare professional to stay updated on this issue or potentially lack of an issue. YOU SHOULD ALWAYS KNOW WHAT’S BEING PUT INTO YOUR BODY BEFORE SOMEONE PUTS SOMETHING INTO IT (this is also true of foods and beverages, except pizza – doesn’t matter what’s on pizza, it will be good for you and tasty).
Medicine, like any profession, has its series of amazing advances where the profession is absolutely right, and then there are some rare times when there is an OOPS! In other words, “experts” told people not to worry and then in time they were wrong! Will this be one of those times? I have no freaking idea! What I do know is a little transparency here is a good thing; it only makes for a better patient and healthcare professional! Again, if it was me I would always want to know what kind of gadolinium agent my local healthcare team was using, but that’s just me. Then I would compare and CONTRAST the one they use to the others in the table above. Get it! Compare and CONTRAST?! Man that is some seriously funny medical humor! I need to quit my day job!
PS. As an update to this research, I have added a second reference from researchers in Belgium and Japan who are concerned that gadolinium-based agents show preliminary evidence of depositing in the cerebellum - an important part of the brain. Again, this is not to scare you but to tell you that they continue to be one of many groups that believe the safest contrast agents (mentioned in the FDA table in this article) should be chosen first and foremost over the others. Makes sense folks!
About Dr. Moyad:
Mark A. Moyad, MD, MPH, currently occupies an endowed position created and funded entirely by the patients he has helped over the past 20+ years. He is the Jenkins/Pokempner Director of Complementary and Alternative Medicine at the University of Michigan Medical Center-Department of Urology. Mark received his medical education from the University of South Florida College of Public Health and the Wayne State University School of Medicine.