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Background- Patients treated for chronic lymphocytic leukemia are frequently administered ibrutinib. Ibrutinib inhibits Bruton’s tyrosine kinase, blocks the B-cell receptor signaling pathway, thereby reducing downstream effects such as proliferation; effectively treating the malignancy. Adverse events such as bleeding have been reported and are suspected to be caused by inhibition of kinases in the platelet aggregation pathway. Clinical Case- A 60-year-old man with chronic lymphocytic leukemia, treated with ibrutinib for five months, was diagnosed with pituitary apoplexy and consequent panhypopituitarism. He presented with a severe headache one month prior to diagnosis. At this time, a non-contrast head CT was interpreted as unremarkable. On second presentation one month later, studies showed a serum sodium of 116 mmol/L (135-145 mmol/L), glucose of 43 mg/dL (65-179 mg/dL), and blood pressure of 95/52. An MRI brain demonstrated an enlarged pituitary with areas of intrinsic T1 hyperintense signal noted within the sella turcica suggestive of blood products. Serum cortisol rose from 0.3 to 8.9 ug/dL (4.5-22.7 ug/dL) one hour after IV injection of 250 mcg cosyntropin. Paired ACTH was < 5 pg/mL (7.2-63 pg/mL). Hydrocortisone was started and blood pressure, sodium, and glucose normalized. LH was 0.9 mIU/mL (3-10 mIU/mL), FSH was 4.7 mIU/mL (1.6-9.7 mIU/mL), and total testosterone was < 0.7 ng/dL (240-950 ng/dL). TSH was 0.115 uIU/mL (0.6-3-3 uIU/mL) with FT4 of 0.84 ng/dL (0.71-1.4 ng/dL). Prolactin was 2.4 ng/mL (4-18 ng/mL) and IGF-1 Z score was -1.28 (-2.0-2.0). Replacement levothyroxine and testosterone were started. Oncology stopped ibrutinib and switched therapy to rituximab and venetoclax. A pituitary MRI two months later showed significant improvement of the T1 hyperintensity (blood products) and a 1.1 cm adenoma was found. During the entire course of his illness his platelet counts ranged from 275 to 431 109/L (150-440 109/L). His INR was 1.14 and PT 13.2 sec (10.2-13.2 sec). He has recovered well on hormone replacement. Discussion- Pituitary apoplexy often has underlying risk factors, including pituitary adenomas and coagulopathies. To our knowledge apoplexy has not been reported in patients taking ibrutinib, though bleeding and platelet dysfunction have been well described. Knowledge of the possible side effects of newer anti-cancer drugs is increasingly important for the endocrinologist.

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