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A recent review article by Ramalho et al summarizes the literature on gadolinium-based contrast agents or GBCAs that are administered for contrast-enhanced MRIs, and it ties together information on agent stability, and animal and human studies. The article, “Gadolinium-Based Contrast Agent Accumulation and Toxicity: An Update”, also emphasizes that the low-stability agents are the ones most often associated with brain deposition of gadolinium that has been reported in the literature since 2014.
Since the article has Open Access at AJNR.org, I will not go into all of the details of it. However, there are some facts contained in the paper that I want to present here that are relevant to why GadoliniumToxicity.com exists. In 2014, Hubbs Grimm and I created this website as a way to alert people to a problem that was not yet recognized by the FDA and medical industry. That problem was gadolinium retention in patients with normal renal function. We knew the facts were in the published literature, but they just had not been seen by the right people yet. Thankfully, that has now begun to change.
Nephrogenic Systemic Fibrosis (NSF)
No review of GBCAs would be complete without some background information on NSF.
In 2006, the association between the administration of GBCAs and the development of Nephrogenic Systemic Fibrosis (NSF) in patients with severe renal disease was reported by Grobner and then by Marckmann et al. NSF predominantly involves the skin, but it is a systemic disease that may also affect other organs such as the lungs, liver, heart, and muscles. The exact pathophysiology of NSF remains unknown, but as the review states, the dissociation of gadolinium ions from their chelating ligands has been accepted as the primary etiology. That is more likely to occur in patients with renal failure than in those with normal renal function since the excretion rate is reduced in those with renal failure. The article indicates that most cases of NSF reported in the literature have been associated with the administration of nonionic, linear gadodiamide (Omniscan, GE Healthcare), nonionic, linear gadoversetamide (OptiMARK, Covidien), and with ionic, linear gadopentetate dimeglumine (Magnevist, Bayer HealthCare Pharmaceuticals).
After limiting the use of GBCAs in patients with renal failure and using more stable GBCAs, there have been no new cases of NSF reported since mid-2009. According to the paper, from 2009 to 2014, confidence in the safety of GBCAs had been largely restored. However, since 2014, numerous studies have been published that reported finding evidence of gadolinium deposition in neural tissues in patients with normal renal function. (more…)
Since early 2014, there have been numerous articles published that report finding evidence of gadolinium deposition in the brain within the dentate nucleus (DN) and globus pallidus (GP) in patients with normal renal function. The findings seem to have come as a surprise to some radiologists, but a review article by Huckle et al indicates that no one should be surprised by the findings. The article, Gadolinium Deposition in Humans – When did we learn that Gadolinium was deposited in vivo?, takes a retrospective look back at gadolinium-based contrast agents (GBCAs) to describe the historical evidence of gadolinium (Gd) deposition in vivo. According to the authors, it “shows that deposition in the basal ganglia should come as no surprise”.
The article notes that deposition of gadolinium in animals with normal renal function has been described in the peer-reviewed literature since at least 1984 when Weinmann et al reported that although gadolinium elimination in rats was largely complete 7 days after administration of Gd-DTPA, a small fraction (0.3%) was retained. Other animal studies confirmed gadolinium retention that was proportional to the dose. Gadolinium was found in bone, skin, and other organs in animals.
The higher stability of macrocyclic GBCAs compared to the linear agents has been confirmed in published animal studies. However, while higher levels of gadolinium were detected in the skin and bones of animals injected with linear agents, the studies demonstrated that “quantifiable levels of gadolinium” are deposited after administration of all GBCAs – linear and macrocyclic agents.
We have some important news to share with patients with normal or near normal renal function who have developed unexplained symptoms since their exposure to gadolinium-based contrast agents (GBCAs). The disease we have been dealing with now has a name: Gadolinium Deposition Disease or GDD.
UNC Radiologist, Richard Semelka, MD, has given us permission to publish his “Initial Draft” of the Disease Description for Gadolinium Deposition Disease on our website; to our knowledge, this is the first time it has been published. Dr. Semelka said that this statement is a work in progress, and he intends to revise and expand it as he learns more about patterns of the disease. If important changes are needed, a revised Disease Description will be published.
While his research is ongoing, Dr. Semelka felt that it was important to release the Disease Description now, so that GDD is recognized as an entity by an expert, which he believes should be very important for sufferers. Dr. Semelka wants to get the initial description of the disease out into the community to start to provide relief and benefit to patients affected by retained gadolinium.
Gadolinium Deposition Disease. Disease Description.
Author: Richard C Semelka, MD. November/2015
Gadolinium Deposition Disease (GDD) is a disease process observed in subjects with normal or near normal renal function who develop persistent symptoms that arise within hours to 2 months following the administration of gadolinium based contrast agents (GBCAs). In these cases, no pre-existent disease, or subsequently developed disease of an alternate known disease process, is present to account for the symptomatology.
Patient symptoms are similar but not identical to those observed in the condition Nephrogenic Systemic Fibrosis (NSF). Typical clinical features include persistent headache and bone and joint pain. More distinctive features are comparable to those observed in NSF, but to a lesser extent; patients often experience subcutaneous soft tissue thickening that clinically appears somewhat spongey, without the hardness and redness observed in NSF. Tendons and ligaments in a comparable distribution may also appear thickened and painful. Patients may complain of a tightness of the hands and feet that resemble the feeling of being fitted with extremely tight gloves or socks. Patients may experience excruciating pain typically in a distal distribution of the arms and legs but may also be torso or generalized in location. This pain is often described as ‘cutting’ or ‘burning’.
Supporting laboratory evidence.
In the early months following development of the disease patients should exhibit elevated blood, urine or other tissue gadolinium levels. The exact levels necessary are not yet determined. Bone gadolinium deposition is likely present for many years following disease development. In the early months after disease development, it may be of value to show elevated gadolinium deposition in some fluid or tissue to establish the diagnosis.
As affected patients ourselves, we want to thank Dr. Semelka for publicly recognizing that patients with normal renal function are retaining gadolinium from administered GBCAs, and that they are being adversely affected by its toxic effects.
Sharon Williams and Hubbs Grimm
You can learn more about Dr. Semelka at: https://www.med.unc.edu/radiology/Dept-info/faculty-staff/faculty-pages/richard-semelka-m-d
Dr. Semelka co-authored a recently published study by Ramalho et al, High Signal Intensity in Globus Pallidus and Dentate Nucleus on Unenhanced T1-weighted MR Images: Evaluation of Two Linear Gadolinium-based Contrast Agents.
Editorial – Last December, I posted a Viewpoint titled “Gadolinium Retention – Is it all in my head?” When I wrote that, I believed I had retained gadolinium in my brain, thyroid gland, and various other parts of my body. I believed it, but I did not know it for sure. It is one thing to think it, but it causes totally different feelings when you have confirmation that you have retained a toxic metal in your body.
On April 8, 2015, I posted about the gadolinium found in my thyroid tissue that was removed 51 months after my 5th dose of a linear gadolinium-based contrast agent. In July, I learned that an analysis of my 2012 non-contrast brain MRI found evidence of gadolinium deposition in the globus pallidus; that MRI was performed exactly two years after my last dose of contrast. Because of recently published studies, I was not surprised that they detected residual gadolinium in my brain. At the time of my MRIs, except for hypertension and a past history of migraine headaches, I had no history of anything known to alter the blood-brain barrier. Then and now, I continue to have “normal” renal function with an eGFR >60, but yet, I have evidence of long-term retention of gadolinium in my body. If I only had gadolinium in my tissues and no symptoms, I might not worry about it as much, but that is not the case. (more…)