CAR T-cell therapy linked to endocrine adverse events in FAERS analysis

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Frontiers in Medicine Published April 16, 2026 Medically reviewed April 25, 2026 DOI ↗ By Dr. Amelia Tan, PhD · Internal Medicine & Chronic Disease

Key Takeaway

Consider proactive endocrine monitoring in CAR T-cell therapy patients, particularly during cytokine release syndrome.

This study was a retrospective disproportionality analysis and structured literature review using data from the FDA Adverse Event Reporting System (FAERS) database from 2017 to the second quarter of 2025. It focused on patients receiving CAR T-cell therapy, with 269 endocrine adverse event reports analyzed. The primary outcome was endocrine adverse events associated with CAR T-cell therapy, and no comparator was reported.

Main results showed 14 significant disproportionality signals for endocrine adverse events, including a reporting odds ratio of 14.93 for estrogen deficiency. Hyperglycemia was the most frequently reported event, with a 39% incidence, and it was associated with cytokine release syndrome (CRS). Mortality was frequently reported among cases with positive endocrine signals, indicating an increased risk when co-occurring with CRS, though exact numbers and statistical measures were not reported.

Safety data identified adverse events such as hyperglycemia, estrogen deficiency, adrenal insufficiency, hypothalamo-pituitary disorders, Hashimoto's thyroiditis, and central diabetes insipidus, with mortality as a serious adverse event; discontinuations and tolerability were not reported. Key limitations include that endocrine adverse events remain poorly characterized and FAERS data have inherent limitations of disproportionality analysis, such as potential reporting biases. The practice relevance is that proactive monitoring of endocrine function, especially in patients experiencing CRS, is warranted, but FAERS signals are disproportionality analyses, not direct incidence rates, and clinical evidence is based on case reports and retrospective studies.

Study Details

Study typeCohort

EvidenceLevel 3

PublishedApr 2026

View Original Abstract ↓

BackgroundChimeric antigen receptor (CAR) T-cell therapy is increasingly used for hematologic malignancies, yet the spectrum and clinical significance of its endocrine adverse events (AEs) remain poorly characterized.ObjectiveTo identify and clinically contextualize signals of endocrine AEs associated with CAR T-cell therapy, with a focus on their overlap with cytokine release syndrome (CRS).MethodsWe performed a retrospective disproportionality analysis using the FDA Adverse Event Reporting System (FAERS) database (2017 to Q2 2025). Reporting odds ratio (ROR) and information component (IC) were calculated for endocrine AEs associated with six CAR T-cell products. To validate and elaborate these pharmacovigilance signals, a structured literature review was conducted to identify published clinical evidence.ResultsThe FAERS analysis identified 269 endocrine AE reports, yielding 14 significant disproportionality signals. Hyperglycemia was the most frequently reported event, while estrogen deficiency showed the strongest signal strength (ROR₀₂₅ = 14.93). Signals for adrenal insufficiency and hypothalamo-pituitary disorders were primarily associated with axicabtagene. Critically, mortality was frequently reported among cases with positive endocrine signals, particularly when the endocrine AE co-occurred with CRS. The literature review provided direct clinical validation: a retrospective study confirmed a 39% incidence of CRS-associated hyperglycemia, and independent case reports documented the first instances of CAR T-cell therapy-induced Hashimoto’s thyroiditis and central diabetes insipidus. These clinical cases corroborated the FAERS signals and suggested immune-inflammatory mechanisms, often independent of corticosteroid use.ConclusionThis integrated analysis reveals a distinct spectrum of CAR T-cell-related endocrine toxicities, encompassing glucose and calcium dysregulation, pituitary axis disorders, and autoimmune phenomena. The frequent and potentially fatal overlap with CRS underscores the need for enhanced clinical vigilance. Proactive monitoring of endocrine function, especially in patients experiencing CRS, is warranted to mitigate these underrecognized complications.