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Editorial by Sharon Williams
While being in the middle of the COVID-19 pandemic might not seem like the best time to write an editorial about long-term gadolinium retention, waiting longer was not a good option for me. I believe that the information I want to share with patients, doctors, and gadolinium researchers needs to be in the public domain.
Anyone who follows our posts knows that none have been made since mid-2019. I will not go into all the reasons for that, but one of the issues resulted in the removal of my ovaries late last year. Thankfully, no cancer was found, but something else that should not have been there was – gadolinium. Testing performed by Doctor’s Data determined that there was gadolinium in both of my ovaries which were removed more than 9.5 years after my last dose of a gadolinium-based contrast agent (GBCA). I must admit that I was not surprised, since gadolinium was also found in my thyroid tissue that was removed in 2014.
At the time of all my MRIs, I had what the NSF literature refers to as “normal” renal function, meaning an eGFR greater than 60. I have had 5 MRIs with a linear GBCA that is no longer on the market, and my last dose was 10 years ago in March of 2010. I have no history of brain tumors or cancer anywhere in my body. Based on what patients like me have been told, I should not have retained gadolinium from the contrast agent, but I did, and I have proof of long-term gadolinium deposition in my organs. While I understand that deposition alone does not prove causation, I believe it raises serious questions about the long-term effects of gadolinium retention that need to be answered.
You might be wondering if I made the FDA or anyone else aware of the fact that gadolinium was found in my ovarian tissue 9.5+ years after my last dose of a GBCA, and the answer is, yes, I did. I sent the FDA and more than 20 other doctors and scientists a copy of a document that contained details of my GBCA history and results of testing my blood, urine, and thyroid and ovarian tissue for gadolinium. While I heard back from the FDA and a few doctors, nothing else has come from it at this time.
Whether the gadolinium level in my tissue was high or not is not the issue since gadolinium should not remain in the body many years after MRIs with a GBCA. As the FDA noted on page 16 of its Briefing Document for the September 8, 2017, MIDAC public meeting about Gadolinium Retention, “detection of gadolinium weeks or months following GBCA administration is considered abnormal as gadolinium is a trace element and not involved in any physiologic processes.” Sherry et al. (2009) reported that gadolinium is toxic in biological systems that require calcium for proper function due to the very similar radius of the Gd3+ and Ca2+ ions. Surely, based on what we have learned about gadolinium (Gd) and Nephrogenic Systemic Fibrosis (NSF), no one can honestly think that patients who retain toxic gadolinium for many months or years will not be harmed by it in some way at some point in time.
Until mid-2015, the FDA had not recognized that patients with normal renal function were retaining gadolinium from GBCAs administered for MRIs. While the FDA and Radiology community now acknowledge that everyone who has an MRI with a GBCA likely retains gadolinium from each dose of contrast they receive, so far, they continue to say that they have seen no evidence that retained gadolinium causes harm. I find that statement hard to reconcile with what we know already from the published facts about NSF, GBCAs, and the toxic effects of gadolinium.
While some may think the long-term effects of gadolinium retention are still unknown, I cannot believe it is a benign substance since I continue to experience symptoms of gadolinium toxicity more than 10 years later. It seems clear that a gadolinium study to evaluate patients like me is urgently needed. In my opinion, the issue is not about the toxic effects of gadolinium when it is retained in the human body since the NSF-related literature already informed us about that. The problem is no one understands what it is doing to patients with normal renal function when less gadolinium may have been retained.
As we have said many times before, Gadolinium Toxicity is a “Disease of Degrees” with NSF being the worst manifestation of it when large amounts of gadolinium are retained. However, based on the published facts about gadolinium and GBCAs, we see no reason to think that retained gadolinium will cause full-blown NSF or nothing at all.
It is my belief that the medical community will not fully-appreciate the scope of the problems related to gadolinium retention until symptomatic patients with normal renal function are interviewed, examined, and tested. If all patients retain some gadolinium from every dose of contrast that they receive, why is it that only a small percentage of people report having symptoms of toxicity? Could asymptomatic patients who have retained Gd go on to develop gadolinium-induced health issues later? Why are patients who have received macrocyclic agents for their MRIs experiencing intense symptoms; could they be retaining the intact macrocyclic GBCA?
There are many unanswered questions about the long-term effects of gadolinium retention, and I believe patients who have been affected by the toxic effects of gadolinium are key to finding some of those answers. What you learn from patients like me might help guide new research.
Researchers interested in conducting a study with me or other patients with normal renal function who have evidence of gadolinium retention and symptoms of gadolinium toxicity, should email me at Sharon@GadoliniumToxicity.com. I sincerely hope that researchers contact me since this problem is not going away.
9/8/2017 FDA Briefing Document for Medical Imaging Drugs Advisory Committee Meeting about Gadolinium Retention. https://www.fda.gov/media/107133/download
Sherry, A. D., Caravan, P., & Lenkinski, R. E. (2009). Primer on gadolinium chemistry. Journal of Magnetic Resonance Imaging : JMRI, 30(6), 1240–1248. Retrieved from http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2853020&tool=pmcentrez&rendertype=abstract
12/19/2017 & 5/16/2018 FDA Safety Announcements can be found here:
Coauthors of The Lighthouse Project provide facts about Gadolinium Toxicity to FDA Advisory Committee
As coauthors of The Lighthouse Project, we have provided written comments about the toxic effects of gadolinium and gadolinium retention in patients with normal renal function to the FDA’s Medical Imaging Drugs Advisory Committee in advance of its September 8, 2017 meeting. We will be making a brief oral presentation during the Open Public Hearing portion of the meeting which will be held at the FDA’s White Oak Campus in Silver Spring, Maryland.
Our comments are built around the following 6 major points that we cover in making the case that the FDA needs to take action regarding the use of Gadolinium-based Contrast Agents (GBCAs) administered for contrast-enhanced MRIs.
1. Medical literature documents toxicity of gadolinium and systemic implications.
2. The Risk Factors for adverse results are many.
3. NSF-Like Symptoms in patients with normal renal function.
4. Gadolinium from GBCAs does not clear the body in a few days, or even in a few months, allowing plenty of time for the Gd ion to dissociate from the chelate.
5. Underreported Symptoms from Contrast MRIs is a serious problem.
6. There is evidence of clinical implications of gadolinium deposition.
Our detailed comments can be found here: Comments-from-Lighthouse-Project-FDA-2017-N-1957 . We also included the following supporting materials:
- Sharon’s 2012 Letter to the FDA (SWilliams-2012FDALetter-FDA-2017-N-1957)
- Our Symptom Survey of the Chronic Effects of Retained Gadolinium from Contrast MRIs (Lighthouse Symptom Survey copy for Docket FDA-2017-N-1957), and
- Our most recent report, Gadolinium Retention from Contrast MRIs in 70 Cases with Normal Renal Function – 24-hour Urine Test Results (Lighthouse 70 Case Retention Study copy for Docket FDA-2017-N-1957)
We will report back later about our experience at the FDA Advisory Committee Meeting.
Sharon Williams and Hubbs Grimm
On September 8, 2017, the FDA’s Medical Imaging Drugs Advisory Committee (MIDAC) will meet to discuss the potential risk of gadolinium retention in the brain and other body organs in patients receiving gadolinium-based contrast agents (GBCAs) for MRI procedures.
During the Open Public Hearing (OPH) portion of the meeting, 75 minutes have been allotted to interested persons to present data, information, or views, orally or in writing. The deadline for requesting time to speak has passed. However, interested parties have until September 7, 2017 to submit electronic or written/paper submissions related to the issue of gadolinium retention. Note that the Docket No. for the meeting is FDA-2017-N-1957 and it must be included on all submissions
An updated announcement about the meeting can be found here: https://www.fda.gov/AdvisoryCommittees/Calendar/ucm571112.htm
CDER (Center for Drug Evaluation and Research) plans to provide a live webcast of the September 8, 2017 MIDAC meeting. Information about the web address for the webcast will be made available at least 2 days before the meeting. See the updated announcement for more information about the webcast.
The Medical Imaging Drugs Advisory Committee Meeting Briefing Document titled, Gadolinium Retention after Gadolinium Based Contrast Magnetic Resonance Imaging in Patients with Normal Renal Function, is available for download: https://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/MedicalImagingDrugsAdvisoryCommittee/UCM572848.pdf
Sharon Williams and Hubbs Grimm have submitted comments and supporting materials from The Lighthouse Project at GadoliniumToxicity.com for Docket No. FDA-2017-N-1957.
Editorial – May 25, 2017
I am very disappointed and frustrated by the May 22, 2017, FDA Safety Announcement about gadolinium-based contrast agents (GBCAs). I am beginning to wonder how many more people must be adversely affected by retained gadolinium before the FDA decides to take decisive action.
Personally, I don’t blame the FDA or radiologists for what happened to NSF patients. What happened to those patients was terrible, but I want to believe that no one knew then just how unstable the linear agents are, especially when they remain in the body for longer periods of time like they might do in renally-impaired patients. However, once the connection between NSF and GBCAs was discovered in 2006, that all began to change. No longer could the FDA and radiology community say that they didn’t know that gadolinium might be retained from MRI contrast agents or what it might do to the human body when that occurred.
From 2006 until the end of 2013, the FDA and medical community thought that only patients with severe renal problems were at risk of retaining gadolinium. Warnings were issued and action was taken to better screen renally-impaired patients and reports of new cases of Nephrogenic Systemic Fibrosis (NSF) dropped dramatically. However, no one seemed to be investigating what might happen when less gadolinium was retained such as what might occur in patients with “normal” renal function or eGFRs greater than 60.
Since December of 2013 and the first paper by Kanda and his colleagues, the evidence has been mounting that clearly shows that patients with normal renal function retain gadolinium in their brains, bones, and elsewhere in their bodies. This seemed to be news to the FDA and radiology community, but it was something that patients affected by gadolinium have long been trying to tell their doctors. I first brought it to the attention of the FDA in my letter of October 23, 2012. In that letter, I noted that evidence of gadolinium retention in patients with normal renal function was reported by Gibby et al. in 2004 – that was 13 years ago, and it occurred after administration of both a linear and a macrocyclic GBCA.
The published literature clearly states that “gadolinium is toxic”. The FDA has acknowledged that “all GBCAs may be associated with some gadolinium retention in the brain, and other body tissues”. So why is it okay to keep injecting the least stable gadolinium-based contrast agents into patients when it is highly likely that those people are going to retain some unknown amount of a toxic metal? Gadolinium is a toxic metal that has been found to be neurotoxic, to impair mitochondrial function, induce oxidative stress, and much more. Researchers are looking for histological changes in the brain, but what about functional changes? (more…)