When Bad Becomes Worse: A Complex Case of Hypophysitis Causing Severe Hyponatremia in the Setting of Immune Checkpoint Inhibitor Therapy and Pituitary Metastasis

Introduction: Immune checkpoint inhibitors (CPI) are immunotherapy drugs that have revolutionized cancer therapy by enhancing the immune response against tumor cells. However, their use is associated with life threatening complications such as hypophysitis, pituitary gland inflammation. Unrecognized secondary adrenal insufficiency in these cases could result in hyponatremia. We present a case of severe hyponatremia caused by CPI use and pituitary metastasis. Case Description: 76-year-old woman with papillary thyroid cancer treated with thyroidectomy and metastasized angiosarcoma of the breast, presented with asymptomatic hyponatremia of 118 mmol/L. She had been receiving nivolumab and ipilimumab for 2 months prior to presentation. She was hemodynamically stable. Physical exam was unremarkable; patient was euvolemic. Chemistry showed a sodium 118 mmol/L with normal renal function. Other electrolytes were normal. Nephrology was consulted for management of hyponatremia. Further workup revealed urine sodium 123 mmol/l, urine osmolality 415 mmol/l and serum osmolality 255 mosm/kg; findings consistent with Syndrome of Inappropriate Antidiuretic Hormone (SIADH). Interestingly, morning cortisol was 2.4 mcg/dL with a suppressed ACTH of <0.1 pg/mL consistent with SIADH caused by secondary adrenal insufficiency most likely due to CPI use. Brain MRI revealed an enlarged pituitary gland. She was started on hydrocortisone 25 mg twice daily which resulted in improvement of her sodium level from 118 mmol/L to 127 mmo/L in 24 hours. In 48 hours, sodium was 134 mmol/L and remained stable thereafter. Patient was discharged on hydrocortisone 15 mg in the am and 5 mg at 2 pm. Discussion: We have portrayed a very interesting presentation of isolated hyponatremia due to central adrenal insufficiency due to CPI use. Understanding the mechanisms underlying CPI-induced hypophysitis is crucial for early detection and management. The current theory is that T-cell activation leads to immune-mediated destruction of pituitary cells, hence affecting synthesis of pituitary hormones. Severe hyponatremia could prompt a nephrology consult as a first approach by primary teams and therefore, recognizing this etiology for hyponatremia in the setting of CPI use could be essential in assertive treatment.