MON-066 - Putting the CAR-T before the Horse: A Case of Panhypopituitarism in the Setting of CAR-T Cell Therapy.

Chimeric antigen receptor (CAR) T-cells, genetically modified T cells made to target tumor antigens, are an effective therapy for oncologic diseases such as acute lymphoblastic leukemia and multiple myeloma. Common adverse effects include neurotoxicity and cytokine release syndrome (Adkins 2019). While endocrine dysfunction and hypophysitis are well-recognized adverse effects in other immunotherapies such as CTLA4 and PDL1 inhibitors (Castillero 2019; Pallin 2018), they have not been routinely documented in the setting of CAR-T cell therapy (Shah 2025). We present a case of CAR-T therapy-associated hypophysitis leading to pan-hypopituitarism.

An 81-year-old male with a history of multiple myeloma in remission s/p CAR-T cell therapy (last treatment 6 months prior to admission) was admitted for UTI with his course complicated by sepsis, hypernatremia, and persistent hypotension. He was treated for nephrogenic vs. central diabetes insipidus by nephrology early in the hospital course, with endocrinology was consulted later for hypotension and adrenal insufficiency. During hypotension workup, TSH was found to be 2.255 uIU/mL (0.4-4.00) with a free T4 at 0.49 ng/dL (0.8-1.5), concerning for central hypothyroidism. This prompted further work up showing central hypogonadism, LH < 0.5 mIU/mL (1.2-8.6), FSH 0.8 mIU/mL (1.3-19.3), testosterone < 4.33 ng/dL (300-1080), with GH 0.1 (0-10) and IGF-1 41 ng/mL (40-194) and prolactin 25.6 ng/mL (1.4-24). ACTH 3 pg/ml (7.2-63) and cortisol 1.4 mcg/dL (2-14) were obtained while the patient received steroids. A brain PET/CT seven months prior showed stable focal uptake in the pituitary fossa. A pituitary MRI showed persistent enhancement and T2/FLAIR hyperintense signal within midline structures, involving the hypothalamus, suggestive of “autoimmune, inflammatory, and demyelinating etiologies,” without evidence of adenoma or stroke sequelae. The constellation of clinical symptoms, biochemical testing, and radiography suggests panhypopituitarism in the setting of CAR-T cell therapy. Currently, the patient is inpatient receiving levothyroxine and hydrocortisone with outpatient consideration of testosterone replacement.

Endocrine-related adverse events secondary to CAR-T cell therapy remain sparse in the literature. A recent large retrospective pharmacovigilance study identified that approximately 0.1% of CAR-T cell adverse events were endocrine events, with 15 cases of hypopituitarism/hypophysitis (representing 27% of the endocrine events) (Shah 2025). Our case highlights that panhypopituitarism and hypophysitis must be included in the differential for patients with signs of axis dysregulation after receiving CAR-T therapy. As this transformative therapy becomes widespread, endocrinologists should remain vigilant for the potential pituitary effects of CAR-T therapy.

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