Case Presentation: A 56-year-old woman presented with 3 days of fatigue, generalized weakness, paresthesia of the feet, and cramping of the lower extremities. Medical history included metastatic serous endometrial cancer which was refractory to first-line treatment with carboplatin and paclitaxel. The patient was subsequently enrolled in a clinical trial and initiated treatment with darvalumab and monalizumab, both immunotherapy agents. Her vitals were unremarkable. She had slight motor weakness in her extremities with preserved sensation and reflexes. Laboratory abnormalities included an elevated serum creatinine meeting criteria for acute kidney injury, metabolic alkalosis (bicarbonate 29 mmol/L), hypomagnesemia (magnesium 0.9 mg/dL), hypokalemia (potassium 3.2 mmol/L), and hypocalcemia (calcium 7.5 mg/dL). The patient had resolution of her symptoms with electrolyte repletion, but continued to require daily potassium and magnesium repletion. Further workup included a renal biopsy that demonstrated acute tubular necrosis and a high-fractional excretion of magnesium (43%; normal < 3%) consistent with an acquired Gitleman-type syndrome. The etiology of both were suspected to be an immune-mediated adverse event from the immunotherapy. Corticosteroids were initiated without improvement in electrolyte wasting. Three months after discharge, the patient continued to require daily oral potassium and magnesium supplementation, along with weekly intravenous magnesium infusions.
Discussion: Cancer treatment regimens featuring immunotherapy agents are now commonly encountered while caring for hospitalized patients. Immune checkpoint inhibitors, in particular, have demonstrated considerable promise for the treatment of melanoma and non-small cell lung cancer. Unfortunately, these agents have been associated with a broad range of immune-mediated adverse events (imAEs), including enterocolitis, hepatitis, pneumonitis, endocrinopathies, and nephritis. The general management of imAEs is initiation of high-dose corticosteroid therapy, followed by a slow taper over the course of a month or more. Acquired Gitelman-type syndrome, as our patient was diagnosed with, is rarely described in the literature. It is unclear whether the acquired Gitelman-type syndrome in this case was the result of one of the immune checkpoint inhibitors or the result of combining these two specific agents.
Conclusions: As the use of immunotherapy agents becomes more common in cancer treatments, hospitalists will encounter patients with imAEs that range from more common presentations to rare ones, such as an acquired Gitelman-type syndrome. Early recognition of an imAE by hospitalists can aid in the rapid initiation of treatment, which has the potential to decrease morbidity and mortality in this fragile patient population.