Endocrine Abstracts

Cyclophosphamide is an alkylating agent used in the treatment of malignant and autoimmune diseases. Severe hyponatraemia is a serious electrolyte disorder with life threatening neurological sequelae. We report a case of recurrent severe, symptomatic hyponatraemia that developed in a 61 year old female with systemic vasculitis and Sjogrens syndrome following low-dose cyclophosphamide.

Case report: A 61 year old lady, with ANA positive systemic vasculitis presented for her first cycle of low dose cyclophosphamide (12 mg/kg). She was prehydrated with 1 l of normal saline and drank 3 l of water for prophylaxis of haemorrhagic cystitis. 30 h post treatment her serum sodium fell from 135 mmol/l pre-treatment to 116 mmol/l with decreased GCS, requiring ITU admission. Her urinary sodium was 121 mmol/l, urine osmolality 347 mOsm/kg with a plasma osmolality of 240 mOsm/kg. She received hypertonic saline and recovered without neurological deficits after slow correction over 2 days. Four weeks later, she was admitted to hospital for careful monitoring, at her second cycle, she was again prehydrated. 24 h post treatment her sodium fell to 121 mmol/l with altered consciousness again requiring hypertonic saline. At her third cycle, she was not prehydrated and was commenced on a 1.5 l fluid restriction. Despite fluid restriction, her serum sodium fell from 135 to 129 mmol/l post therapy, without clinical features and corrected spontaneously.

Discussion: Patients receiving cyclophosphamide are at high risk of developing symptomatic hyponatraemia due to SIADH even at low doses of therapy. Cyclophosphamide may induce SIADH, by potentiating the renal actions of AVP. The combination of both increased ADH effect and excess water intake to prevent haemorrhagic cystitis can induce potentially life-threatening hyponatraemia. Clinicians need to be aware of this threat when encouraging large volume prehydration and diuresis with cyclophosphamide therapy. It is possible that pre-hydration with isotonic saline rather than oral water may minimise the incidence of this complication.