The Case of the Vanishing Natrium: Phosphoinositide 3-Kinase Inhibitor Did It!

Introduction: Hyponatremia is a water imbalance disorder seen in 47% of hospitalized cancer patients. It is associated with longer hospital stay and high mortality. We present a case of hyponatremia due to inavolisib, a phosphoinositide 3-kinase (PI3K) inhibitor which is an oral medication used to treat hormone receptor positive, human epidermal growth factor receptor 2 (HER 2) negative metastatic breast cancer. Case Description: 74-year-old woman with history of stage 4 breast cancer, estrogen receptor positive, HER 2 negative, with phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) mutation previously on chemotherapy (Anastrozole and palbociclib; capivasertib and fulvestrant) and radiotherapy developed progressive bone and pulmonary metastatic lesions. Due to side effects, her chemotheray was switched to inavolisib, palbociclib and fulvestrant. She was hospitalized 3 weeks later for generalized weakness and diagnosed with moderate hyponatremia of 122 mmol/L that responded to intravenous fluids, sodium improved to 126 mmol/L but downtrended to 122 mmol/L in a few hours (Figure 1) with symptoms, so hypertonic saline boluses were given which improved her mentation. Hyponatremia initially thought to be due to volume depletion but repeat lab studies (Table 1) were consistent with SIADH (Syndrome of inappropriate diuretic hormone). Due to sodium chloride tablet intolerance, treatment was switched to Urea. Sodium improved to 133 mmol/L at discharge and urea was continued. Discussion: SIADH may be driven by anticancer therapies or ectopic production of antidiuretic hormone by the tumor. Rarely molecularly targeted therapy and immunotherapy such as combination of inavolisib and palbociclib can potentially cause SIADH induced hyponatremia. This case highlights the importance of close monitoring of sodium levels in cancer patients on such therapies.Sodium trend during the hospital stay Laboratory Studies - Timeline Day 1 Day 3 Day 6 Serum Osmolality (mOsm/kg) 275 281 285 Urine Osmolality (mOsm/kg) 264 495 725 Urine Sodium (mmol/L) <5 174 34