Forced diuresis to reduce nephrotoxicity of streptozotocin in the treatment of advanced metastatic insulinoma Streptozotocin is a specific , cell toxin that was first used to treat malignant islet cell tumours in 1%8.' Enthusiasm for its use, however, has been tempered by the high risk of nephrotoxicity, which occurs in up to 100% of patients.2 We report on the successful management of a patient with a malignant insulinoma who sustained renal impairment when treated with streptozotocin alone

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... tolerated repeated administration of the drug without deterioration in renal function when a hydration technique was used to administer the drug. Case report A 65 year old woman presented with a two year history of episodic abdominal pain, anorexia, and weight loss of about 19 kg. A gall bladder calculus was visualised on abdominal ultrasound, and a secretin-pancreozymin test showed impaired bicarbonate secretion. At laparotomy there was a large, unresectable tumour of the body of the pancreas fixed to retroperitoneal structures with multiple hepatic, omental, and mesenteric metastases. Despite this she remained well for 18 months but then developed Whipple's triad of hypoglycaemic symptoms after fasting and exercise, relieved by glucose. She had inappropriately high insulin concentrations with a mean insulin to glucose ratio of9-2, consistent with an insulin secreting tumour. Streptozotocin 500 mg/m2 (700 mg) was infused on three occasions on alternate days. Her symptoms responded, but her renal function steadily deteriorated with a creatinine clearance of only 30 ml/min (figure) and mild proteinuria (250 mg/24 h); further treatment was therefore suspended. Her symptoms recurred one year later, at which stage her renal function had recovered. Based on our experience with another nephrotoxic drug, cisplatin,3 we tried administering streptozotocin accompanied by hydration and diuresis to minimise the renal damage. We restarted streptozotocin at the same dose, but on each occasion the patient was prehydrated intravenously with two litres of normal saline hourly for two hours, and frusemide 40 mg was also given intravenously 30 minutes after the infusion was started. When a good diuresis was established streptozotocin was then given by a second infusion over 60 minutes and the saline infusion was titrated to maintain a total urine output of four to five litres throughout the procedure, which lasted roughly four hours. To date this method has been successfully used for eight treatment schedules, and her renal function has remained stable with a creatinine clearance of about 60 ml/min and normal findings on urine analysis (figure). Comment Ninety percent of patients with malignant islet cell tumours have hepatic metastases at the time of diagnosis, so surgical treatment is usually fl~~~t " tt$ + 70 60-; 50 + / c 40 20 10 12 24 36 Time (months) Creatinine clearance in relation to treatment with streptozotocin (500 mg/in2). Broken arrows represent administration using hydration technique. impracticable. Maintaining a high calorie intake or using diazoxide or long acting somatostatin analogue will help prevent the distressing hypoglycaemia secondary to hyperinsulinaemia but will not affect tumour growth. Since streptozotocin is the only specific agent currently available to treat advanced metastatic islet cell tumours,45 its renal toxicity is a major drawback.2 Using the hydration technique in our patient allowed continued use of streptozotocin without further renal damage and with no indication that its therapeutic efficacy was compromised since the patient remained symptomatically well with a mean insulin to glucose ratio of 5-0 throughout the period. This experience suggests that the nephrotoxicity of streptozotocin can be mitigated by inducing a forced diuresis, atechnique we therefore recommend as definitive treatment for an advanced malignant insulinoma. I Murray-Lyon IM, Eddleston AL, Williams R, et al. Treatment of multiple-hormone-producing malignant islet cell tumour with streptozotocin. Lancet 1968;ii:895-8. 2 SadoffL. Nephrotoxicity of streptozotocin. Cancer ChenotherRep 1970;54:457-9. 3 Hayes DM, Cvitkovic E, Golbey R, es al. High dose cis-platinum diammine dichloride. Amelioration of renal toxicity by mannitol diuresis. Simple thyroid cyst: cause of acute bilateral recurrent laryngeal nerve palsy Upper airway obstruction due to goitre usually results from tracheal compression or invasion. Anaplastic carcinoma, lymphoma, and retrosternal goitre are the common causes. These may also compress or invade the recurrent laryngeal nerves, causing airways obstruction from vocal cord paralysis. We report a case of acute upper airway obstruction secondary to bilateral recurrent laryngeal nerve compression by a simple thyroid cyst. Case report A 40 year old nursing auxiliary was admitted after collapsing in acute respiratory distress. She had a four week history of a steadily enlarging goitre. Four days before admission this had begun to enlarge rapidly, accompanied by hoarseness, stridor, and progressive dyspnoea. She had considerable inspiratory stridor with minimal respiratory distress in the sitting position but could not recline without precipitating acute dyspnoea. There was a smooth, non-tender 3x4 cm swelling limited to the lower pole of the left lobe of the thyroid gland. The results of her thyroid function tests were normal. A chest x ray film and thoracic inlet views showed no evidence oftracheal compression. A laryngologist performed indirect laryngoscopy. This showed complete paralysis of the left vocal cord, which occupied the paramedian position, and paresis of the right cord, which was lying in the semi-adducted position with limited abduction and adduction. She was treated overnight with intranasal oxygen and slept sitting in bed. At operation the next morning a cyst ofthe left lower pole ofthe thyroid was identified. The cyst fluid was translucent and not bloodstained, the rest of the thyroid gland being normal. Frozen section examination of the wall of the cyst showed no evidence ofmalignancy and a left hemithyroidectomy was performed. Complete visualisation of the left recurrent nerve along its course in the neck showed no abnormality. The patient had complete reliefofstridor and respiratory distress immediately after operation, and at extubation both vocal cords were seen to abduct. A check laryngoscopy three days later showed normal position and movement of the vocal cords. Paraffin section histology ofthe left lobe ofthe thyroid showed the changes ofa nodular colloid goitre with a cyst cavity 3 cm in diameter.