Endocrine Abstracts

Introduction: We present a rare case of late-onset hypophysitis in a 16-year-old female with B-cell acute lymphoblastic leukaemia (ALL), which developed following treatment with Blinatumomab, an immune checkpoint inhibitor.

Case presentation: A 16-years-8-month-old girl diagnosed with B-cell ALL at 14-years-9-months was referred for polyuria exceeding 4 ml.kg^-1.h^-1. Initial lumbar puncture confirmed no central nervous system involvement. Her chemotherapy regimen included dexamethasone, peg-asparaginase, methotrexate, mercaptopurine, vincristine, imatinib, and two cycles of intravenous blinatumomab. Her induction chemotherapy was complicated by steroid-induced diabetes, febrile neutropenia with septic shock, perineal abscess requiring debridement and sigmoid colostomy, multiple transfusions, and acute-on-chronic pancreatitis necessitating drainage, stenting, and enzyme supplementation. Upon referral, her height was 164.1 cm (+0.2 SDS), weight 44.2 kg (-1.23 SDS), and BMI 16.4 kg.m^-2 (-1.94 SDS), reflecting significant weight loss since diagnosis. Investigations revealed arginine vasopressin deficiency with hypernatremia (sodium 149 mmol.L^-1)(NR 135-145), elevated plasma osmolality (299 mosm.kg^-1)(275-296), decreased urine osmolality (76 mosm.kg^-1)(200-800), low co-peptin (3.6 pmol.L^-1)(>5), and partial response to DDAVP during water deprivation test. Initially, remainder hypothalamic-pituitary axis screening was unremarkable: TSH 0.48 mu.L^-1 (0.3-3.8), free T4 10.3 pmol.L^-1 (9-19), cortisol 472 nmol.L^-1 (140-500). Neuroimaging revealed absent posterior pituitary bright spot and thickened pituitary stalk; no mass lesion. After commencing oral desmopressin, she developed persistent hypotension, hyponatremia (sodium 132 mmol.L^-1)(135-145), lethargy, and vomiting over the next month. A subsequent lumbar puncture remained normal. Repeat endocrine evaluation indicated secondary adrenal insufficiency (09.00 cortisol 98 nmol.L^-1)(140-500); (ACTH <1.1 pmol.L^-1)(2-11), central hypothyroidism (free T4 6.6 pmol.L^-1, inappropriate normal TSH 0.68 mu.L^-1), low LH (<0.1 IU.L^-1)(3-8) and FSH (0.2 IU.L^-1)(2-6), raised prolactin (1717 mU.L^-1)(0-500), and low IGF-1 (5.1 pmol.L^-1)(24.7-55.8), consistent with panhypopituitarism, presenting 19 months post-blinatumomab. Workup for granulomatous hypophysitis and Langerhans histiocytosis was negative. She showed prompt clinical response to hydrocortisone and levothyroxine and remains under close follow-up.

Discussion: Hypophysitis secondary to immune checkpoint inhibitors is well described with ipilimumab and nivolumab but not reported with blinatumomab. Likely driven by T-cell-mediated pituitary destruction and complement activation, it is typically irreversible and steroid-unresponsive. With other causes excluded, blinatumomab-induced hypophysitis was considered causative.