Endocrine Abstracts

A 56-year-old male presented in 2017 with acute symptomatic hyponatraemia. He was admitted with a seizure and a plasma sodium of 112 mmol/l. His past medical history was notable for alcohol excess and smoking. The acute presentation was managed with 3% hypertonic saline infusion in ITU. Plasma osmolality was 240 mOsm/Kg, urine osmolality 327 mOsm/kg and sport urine sodium 28 mmol/l. CT TAP showed some oesophageal thickening only; endoscopy was normal. He made a good recovery from this episode and was discharged home with a normalised pNa. The patient was followed up in the outpatient clinic. Eight months after discharge, his pNa fell to 122 mmol/l. Repeat biochemistry testing confirmed SIAD; he was asymptomatic and managed as an outpatient with fluid restriction. He subsequently presented with acute appendicitis; CT abdomen showed an abscess but no evidence of malignancy. pNa remained chronically low ranging from 120 to 129 mmol/l. Eighteen months after his initial presentation his pNa dropped to 111 mmol/l; this was associated with generalised fatigue and weight loss. He was admitted for further investigation and management. Repeat CT TAP demonstrated a new 6×4 cm lung tumour with widespread lymphadenopathy and a mass adjacent to the pancreatic head. Biopsy confirmed small cell lung cancer. He was commenced on palliative chemotherapy. He did not respond to fluid restriction and was commenced on Tolvaptan. pNa initially responded well to Tolvaptan incrementing over 10 days to 129 mmol/l. Urine osmolality fell in conjunction with initiation of treatment. He required admission to hospital following his 2^nd and 3^rd cycles of chemotherapy due to worsening hyponatraemia. His Tolvaptan was increased to maximum dose yet there was no sustained improvement in his plasma sodium. Repeat urine osmolality measurement demonstrated a loss of aquaretic effect with urine osmolality ranging from 490 to 590 mOsm/Kg whilst on maximum dose Tolvaptan. This case highlights two key points in the management of chronic hyponatraemia. Firstly the cause of SIAD should be re-evaluated if there is a change in clinical condition e.g. acute drop in plasma sodium or development of new symptoms. Repeat imaging should be considered in patients with risk factors for malignancy who have persistent SIAD but normal initial imaging. Secondly Tolvaptan resistance is an emerging clinical phenomenon in patients with SCLC on long term V2-receptor antagonists with only a few cases reports in the literature. It is thought to be secondary to rising AVP concentrations associated with disease progression.