Gadolinium lexicon may be growing along with concerns

A paper running in the August edition of the American Journal of Roentgenology proposes adding two heretofore unnamed conditions to what the authors call the “family of disorders” linked to the use of gadolinium-based contrast agents (GBCAs).

Lead author Richard Semelka, MD, of the University of North Carolina and colleagues submit that it would be useful to call the histopathologically proven presence of gadolinium in brain tissue “gadolinium storage condition.”

And patients who have normal renal function but still suffer symptoms of gadolinium exposure would be said to have “gadolinium deposition disease.”

These descriptors would join the established nephrogenic systemic fibrosis (NSF) and, as with all pharmaceuticals, severe acute adverse event (i.e., allergic reactions).

Clinical nomenclature

Even in patients with normal renal function, gadolinium contrast is known to show up in body tissues such as bone matrix or brain tissues, Semelka and co-authors point out. They call for using gadolinium storage condition when discussing these gadolinium tissue deposits, evidently on the strength of the new term’s pointedly clinical connotations.

“As is the case with NSF, the least stable GBCAs appear to be most likely to result in gadolinium storage condition, and stable agents either do not cause it or cause it at a very low level,” they note, reminding their readers that macrocyclic agents are more stable than linear agents and have been linked to fewer instances of disease or deposition states.

The clinical significance of gadolinium tissue deposition remains incompletely understood, the authors stress before excerpting a 2015 FDA safety announcement regarding brain deposit of gadolinium:

“It is unknown whether these gadolinium deposits are harmful or can lead to adverse health effects. … To reduce the potential for gadolinium accumulation, health care professionals should consider limiting GBCA use to clinical circumstances in which the additional information provided by the contrast is necessary.”

To this Semelka and colleagues add that it “may be imperative to consider gadolinium retention potential” when deciding which particular GBCA to administer.

Uncommon but potentially formidable

If the new terms win widespread adoption, patients with normal or near-normal renal function who develop persistent symptoms that arise hours to two months after the administration of GBCAs would be said to have gadolinium deposition disease.

In such cases, Semelka and co-authors write, there’s no preexistent disease or subsequently developed disease of an alternate known process is that could account for the symptoms. These are similar but not the same as seen with NSF and have been known to include persistent headache, mental “fog” and pain in the bones or joints.  

And that’s just for starters.

“Patients may complain of tightness of the hands and feet that resembles the feeling of being fitted with extremely tight gloves or socks,” the authors explain. “Patients may experience excruciating pain, typically in a distal distribution, of the arms and legs but that may also be in the torso or generalized in location. This pain is often described as feeling like sharp pins and needles, cutting, or burning.”

On a brighter note, they surmise that gadolinium deposition disease is uncommon.

“Our opinion is that in patients who describe symptoms that suggest the diagnosis of gadolinium deposition disease,” they write, “confirmation of the presence of gadolinium is necessary to establish the diagnosis.”

Evidence-based outlook

Semelka and team recommend 24-hour urine testing for gadolinium, 30 days or more after the most recent GBCA administration.

“Early recognition will facilitate early treatment of the disease before it becomes more chronic and likely less responsive to therapy,” they write.

Assessing future directions, the authors place their terminology proposals in the context of ongoing concerns, which indeed are still arising and commanding attention.

“It is important to improve the understanding of the family of disorders related to gadolinium in humans,” they conclude. “Genetic testing may hold the key to predict who is likely to have NSF, severe acute adverse event, gadolinium storage condition or gadolinium deposition disease, but it is uncertain if such testing will occur or be practical. As genetic testing is not currently a reality to prevent these diseases, early detection and treatment are the focus of management.”