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Relative Adrenal Insufficiency Observed Among Patients With High-Risk Neuroblastoma During Treatment

Relative Adrenal Insufficiency Observed Among Patients With High-Risk Neuroblastoma During Treatment 1024 683 Jessica Nye, PhD

A subset of patients with high-risk neuroblastoma (NBL) and primary adrenal tumors develop an adrenal insufficiency (AI)-like phenotype during treatment.

“We noticed that some of the patients with neuroblastoma had less hypotension when we added hydrocortisone while they were getting dinutuximab therapy. So, we said, I wonder if that has anything to do with the fact that they could be relatively adrenally insufficient because of the different intensive treatments our patients endure,” says Keri A. Streby, MD, the director of the Neuroblastoma Program at Nationwide Children’s Hospital and associate professor at The Ohio State University College of Medicine.

In a paper published in Pediatric Blood & Cancer, Dr. Streby and colleagues retrospectively reviewed records of patients (n=137) with NBL who received treatment at Nationwide Children’s between 1998 and 2021 for signs and symptoms of AI.

The patients with high-risk (n=76) and non-high-risk (n=61) NBL were aged median 2.9 and 0.4 years at diagnosis, 43.4% and 34.4% were girls, 66.2% and 42.6% had primary adrenal tumors and 90.3% and 9.4% had unfavorable histology, respectively.

Signs of AI were observed among 12.0% of patients with high-risk disease compared with 4.9% of patients with non-high-risk disease.

The cumulative incidence of AI in high-risk NBL was 9.9% at 3 years, 12% at 5 years and 14% at 10 years from diagnosis whereas the cumulative incidence of AI was stable at 3.5% at 3 years from diagnosis for non-high-risk NBL.

“There’s not a great way to test for adrenal insufficiency during these treatments, because patients need to be at a good resting or basal state, and our patients have lots of ups and downs as they go through their therapy,” says Dr. Streby. “[Since] we don’t really have the tools to screen [for adrenal insufficiency] during cancer treatment at this point, if you have a patient that’s hypotensive while they’re getting their anti-GD2 antibody therapy, or while they’re in transplant, consider giving them stress dose steroids, because it might help them tolerate their treatments better.”

Among patients with high-risk disease, those with AI had a higher rate of adrenal primary tumors (100%) than those without AI (60.9%; P =.0234).

The median time from diagnosis to AI onset was 10.2 months. All patients with AI underwent both surgical resection and received chemotherapy. The patients who developed AI before surgery (n=3) did so a median of 100 days prior to surgery whereas those who developed AI after surgery (n=6) did so at a median of 353 days after surgery. The timing of AI symptoms suggests adrenalectomy is not the cause of AI in patients with neuroblastoma.

Dr. Streby says that to develop tools to screen for AI during cancer treatment, large, multi-institution studies are needed. “If anyone in endocrinology wants to look into [this gap in clinical knowledge more], obviously we would love to collaborate. It would be fascinating to do a multisite retrospective, or better yet a prospective study. If we could develop a better screening method, then maybe we can prevent adrenal insufficiency symptoms altogether.”

 

Reference:

Srivastsa S, Metzger G, Horvath K, Patterson K, Scruggs M, Bourgeois T, Stanek J, Minneci PC, Aldrink JH, Streby KA. Incidence of Adrenal Insufficiency in Patients With High-Risk Neuroblastoma: A Single-Institution Analysis. Pediatr Blood Cancer. 2025;72(4):e31543.

Image credit: Adobe Stock

About the author

Jessica Nye, PhD, is a freelance science and medical writer based in Barcelona, Spain. She completed her BS in biology and chemistry and MS in evolutionary biology at Florida State University. Dr. Nye studied population genetics for her doctorate in biomedicine at University of Pompeu Fabra. She conducted her postdoctoral research on the inheritance of complex traits at the Autonomous University of Barcelona.

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