The Eyes Cannot See What the Mind Does Not Know: Endocrinological Side Effects of Ibrutinib

Over the last 7 years, ibrutinib has been given US Food and Drug Administration approval for a rising number of indications ranging from chronic lymphocytic leukemia (CLL) and marginal zone lymphoma to Waldenstrom macroglobulinemia.

An 85-year-old man with a history of CLL who had been treated with ibrutinib over 6 weeks developed a rash and progressive weakness, and he was ultimately admitted to the hospital for obtundation. He was hypotensive, hyponatremic, and hypothyroid. Despite extensive testing and treatment for syndrome of inappropriate antidiuretic hormone (SIADH), he remained unimproved. Results of an adrenocorticotropic hormone stimulation test indicated secondary adrenal insufficiency. He was treated with hydrocortisone, and his symptoms subsequently resolved.

Previous studies have demonstrated the presence of endocrine dysfunction, such as adrenal insufficiency, thyroid dysfunction, hyperparathyroidism, and gonadal failure in some tyrosine kinase inhibitors (TKI). To our knowledge, no previous literature has reported this association specifically with the TKI ibrutinib. The case highlights the importance of spreading awareness amongst clinicians of potential side effects that can occur with targeted therapy such as ibrutinib. This, in turn, will facilitate prompt recognition and early management when such cases arise in a hospital setting.