Endocrine Abstracts

A 58-year-old male was admitted through the emergency department with symptomatic severe euvolemic hyponatremia. Biochemistry was consistent with SIAD (plasma sodium (pNa) 107 mmol/l, plasma osmolality 230 mOsm/kg, urine sodium 36 mmol/l, urine osmolality (UOsm) 638 mOsm/kg, 0900 h plasma cortisol 484 nmol/l and thyroid function tests normal). Chest X-ray was normal but CT thorax confirmed a lung mass suspicious for malignancy. As the patient had symptoms of cerebral irritation, including drowsiness and confusion, he was treated with hypertonic (3%) saline infusion; pNa rose by 13 mmmol/l over the 48 h and symptoms resolved. Water deprivation caused no further rise in pNa so the patient underwent tolvaptan challenge; pNa rose from 121 to 125 mmol/l over 12 h, associated with a rise in plasma vasopressin (pAVP) from 4.4–9.3 pmol/l. Tolvaptan 7.5 mg daily was commenced on day 5 and pNa rose gradually to 130 mmol/l with an eventual tolvaptan dose of 15 mg daily. Over 6 weeks, the patient developed persistent hyponatremia despite escalating doses of tolvaptan to 60 mg daily. UOsm while on tolvaptan was >800 mOsm/kg and AVP levels between 8 and 16 pmol/l indicating unopposed action of AVP. Systemic chemotherapy led to temporary improvement in plasma sodium and tolvaptan dose was reduced to 15 mg over the subsequent three months. Six months after initial presentation, pNa fell again and tolvaptan dose was increased to 60 mg; noncompliance was excluded by supervised tolvaptan challenge, during which pAVP rose to 178 pmol/l, and UOsm remained >909 mOsm/kg, suggesting renal resistance to tolvaptan. Imaging confirmed progressive liver and bony metastases and the patient died 10 months after presentation, due to metastatic malignancy. This is the first report of escape of SIAD from tolvaptan therapy, despite increasing doses. With progression of malignancy, and rising pAVP conentrations tolvaptan may have been insufficient to compete with tumour associated AVP for renal receptors.