Letter to the Editor| Volume 364, ISSUE 1, P134-135, July 2022

Much more than thiazide-induced hyponatremia: Checkpoint inhibitor hypophysitis!

      A 74-year-old hemodynamically stable male patient with metastatic renal cell cancer (RCC) presented acutely with mild headache, dizziness, nausea and general malaise progressing over the last four weeks. Laboratory assessment indicated severe hyponatremia as low as 118 mEq/L (normal 136–145). Routine analysis, in addition, indicated minor hypocalcemia of 2.07 mEq/L (normal 2.2–2.5) with a normal serum albumin and hypochloremia with 90 mEq/L (normal 97–107). While clinical volume assessment indicated minor signs of depletion, serum osmolality expectedly proved reduced (250 mM/kg; normal 280–300) with a normal urine osmolality of 571 mM/kg (normal 50–1200). In addition, admission spot urine sodium was measured at 137 mEq/L. Medication review indicated, among others, intake of 12.5 mg hydrochlorothiazide, which was stopped under the assumption of thiazide-induced hyponatremia. Despite severe hyponatremia below 120 mM/L, opening up the opportunity of 3% saline application as per guideline recommendation, however, with a view to the insidious onset we first opted for infusion of 2000 ml/24 h 0.9% normal saline after ICU admission and an unremarkable cerebral CT scan. Serial serum sodium controls every 4 h, however, did not result in laboratory and clinical improvement. Therefore, the oncologic history was reviewed again, revealing kidney-preserving resection of a left-sided clear-cell RCC 11 years before (pT1b, Nx, L0, V1, R0, G3). Multiple metastases were resected over the preceding seven to four years, including pulmonary metastasectomies, pancreatic tail resection, resection of skin and bone metastases. Due to progressive metastatic spread, including diffuse lymph node and bone metastases, the patient was treated with the tyrosine kinase inhibitor (TKI) pazopanib over 24 months. With a view to secondary loss of response, the patient was finally started on cancer immunotherapy involving the PD-1 (programmed cell death protein-1) inhibitor nivolumab 14 months earlier.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to The American Journal of the Medical Sciences
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Chang L.S.
        • Barroso-Sousa R.
        • Tolaney S.M.
        • et al.
        Endocrine toxicity of cancer immunotherapy targeting immune checkpoints.
        Endocr Rev. 2019; 40: 17-65
        • Barroso-Sousa R.
        • Barry W.T.
        • Garrido-Castro A.C.
        • et al.
        Incidence of endocrine dysfunction following the use of different immune checkpoint inhibitor regimens: a systematic review and meta-analysis.
        JAMA Oncol. 2018; 4: 173-182
        • Paschou S.A.
        • Stefanaki K.
        • Psaltopoulou T.
        • et al.
        How we treat endocrine complications of immune checkpoint inhibitors.
        ESMO Open. 2021; 6100011
        • Seethapathy H.
        • Rusibamayila N.
        • Chute D.F.
        • et al.
        Hyponatremia and other electrolyte abnormalities in patients receiving immune checkpoint inhibitors.
        Nephrol Dial Transplant. 2021; 36: 2241-2247