Postgrad Med J: first published as 10.1136/pgmj.53.619.274 on 1 May 1977. Downloaded from Postgraduate Medical Journal (May 1977) 53, 274-276.

Inappropriate anti-diuretic (ADH) secretion in association with carcinoma of the bladder S. B. KAYE E. J. Ross Department of , University College Hospital, London

Summary lateral bladder wall. Biopsy showed a well differen- A case of carcinoma of the bladder complicated by the tiated squamous carcinoma, and treatment was syndrome of inappropriate anti-diuretic hormone started with radiotherapy. secretion is reported. Management of the syndrome is Two days later the patient deteriorated, becoming discussed. drowsy without focal neurological signs, hypother- mic and oliguric. Clinically she was not dehydrated Introduction and her blood pressure was 100/60 mmHg. Ectopic production of anti-diuretic hormone Investigations at that stage showed a haemoglobin (ADH; ) is a well recognized phenome- of 10-4 g/dl; white cell count 12-1 x 109/1; plasma urea non in patients with malignant disease, and was first 4-15 mmol/l; plasma sodium 104 mmol/l; plasma described with carcinoma of the bronchus (Schwartz chloride 75 mmol/l; plasma potassium 4-2 mmol/l; et al., 1957). Confirmation has come from radio- plasma 22 mmol/l; plasmaosmolality 219 immunoassay studies using tumour extracts of mosmol/kg of water; urine osmolality 560 mosmol/kg bronchogenic carcinoma in vitro (George, Capen of water; plasma 718 mmol/l. During the first and Phillips, 1972). 24 hr the total urine output was 100 ml. by copyright. The syndrome has also been described in cases of A diagnosis of inappropriate ADH secretion was carcinoma of the (Lebacq and Delaerc, made and treatment was started with fluid restriction 1965); (De Sousa and Jenny, 1964); to a maximum of 1 litre daily, fludrocortisone 8 mg adrenal cortex (Falchuk, 1973); prostate (Sacks et daily, and 20 ag daily, because of al., 1975); (Haas, Rosey and Choubrac, the possibility of as an added factor. 1975) and in Hodgkin's disease (Cassileth and Trot- Over the course of 10 days her condition im- man, 1973). proved-urine output rose to 800 ml daily, plasma The purpose of this paper is to report a patient sodium rose to 123 mmol/l and to with squamous cell carcinoma of the bladder and 256 mosmol/kg of water. Fluid restriction was there- http://pmj.bmj.com/ inappropriate ADH secretion in whom no other fore lifted, and 1 week later the dose of fludrocorti- cause for the syndrome was found. Treatment of the sone was reduced progressively. She continued to tumour, together with fluid restriction and fludro- improve, and 3 weeks after her initial acute deterio- in large doses, resulted in a temporary ration she was able to resume radiotherapy, which clinical and biochemical recovery. This association was completed with no ill effects. At that stage appears not to have been previously reported. plasma sodium concentration was normal, but 2 weeks later fell again to 124 mmol/l requiring a Case report further course of fludrocortisone. Fluid restriction on September 30, 2021 by guest. Protected A 77-year-old retired school teacher presented to was not reimposed. the surgical clinic with a 3-month history of consti- The patient remained clinically well for a further pation and frequency of micturition. Apart from a 6 weeks, but then deteriorated with abdominal pain partial thyroidectomy for Graves' disease when aged and signs of peritonitis. Plasma sodium fell to 122 30 years, her general health had been good and she mmol/l (on fludrocortisone 0-4 mg daily), the patient was taking no regular medication. became severely oliguric and died 4 months after No abnormality was found on clinical examina- commencement of radiotherapy. tion; initialinvestigation showed a plasma sodium of At post-mortem a vesico-peritoneal fistula related 130 mmol/l (130 mEq/l), but was otherwise normal. to the ulcerating bladder carcinoma was found. A Barium enema was also normal, but an intravenous metastasis was seen in one lumbar vertebra, but there pyelogram demonstrated a filling defect suggestive of was no evidence of spread elsewhere; in particular tumour in the bladder. the was normal. One normal sized She was admitted to hospital for cystoscopy, at lobe of was identified. which a large tumour mass was seen on the right Thyroid function tests subsequently available Postgrad Med J: first published as 10.1136/pgmj.53.619.274 on 1 May 1977. Downloaded from T. ME.....q...,...... ·· Case reports 275 Imr't.-:.0 .f\

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. PlasmaijArsodium and urine output from presentation until ''."; ' ?..''·· '. ·..;."'.. " . , :/:::;,S *-; FIG. 1. Plasma sodium and urine output from presentation until by copyright. death. (both at the onset of symptoms and 3 weeks after hypopituitarism, hypothyroidism and acute por- stopping thyroxine) showed a low plasma thyroxine; phyria (Bartter, 1970). The evidence in this case, 29-6-34-0 mmol/l (normal range 51-2-157-0 mmol/l), however, points strongly to ectopic production of a low plasma triiodothyronine; 0-20-0-39 mmol/l ADH by the bladder tumour. Carcinoma of the (normal range 1-23-3-07 mmol/l) and a normal bladder has previously been reported as responsible thyroid-stimulating hormone (TSH) of < 1 0 mmol/l. for ectopic secretion of parathyroid hormone (Svane, In the absence of hypopituitarism these results are 1964), and the production of another polypeptide http://pmj.bmj.com/ interpreted as illustrating the well recognized effect hormone such as ADH is therefore not unexpected. of severe chronic illness on thyroid function in Since the syndrome of inappropriate ADH secre- euthyroid patients (Carter et al., 1974); they would tion was first described, fluid restriction and hyper- not substantiate a diagnosis of primary hypothy- tonic saline infusion have been accepted forms of roidism. treatment. The former, however, is tedious and the Urinary ADH secretion is thought to correlate latter is largely ineffective. well with concentration. A more recent for plasma Radioimmunoassay proposal rapid correction of on September 30, 2021 by guest. Protected on an initial urine sample was therefore performed hyponatraemia has been the use of intravenous by using preheated porous silica beads for extrac- frusemide with replacement of urinary tion of the hormone (Khokhar, Ramage and Slater, losses (Hantman et al., 1973). For management of 1975). This gave a value of 341 pg/ml, markedly chronic hyponatraemia due to inappropriate ADH elevated and undoubtedly inappropriate for the secretion, long term treatment with oral levels of plasma and urine osmolality at that stage (White and Fetner, 1975) or oral demethylchlortetra- (normal value up to 156 pg/ml in normally hydrated cycline (De Troyez and Demanet, 1975) has been individuals). suggested. An attack on the tumour responsible remains, -however, the basis of management when- Discussion ever possible, and was at least partly effective in this Though inappropriate ADH secretion is perhaps case. best known in the context of malignant disease, it is Fludrocortisone in high dosage was advocated for also known to occur in other clinical situations. correction of hyponatraemia in 1963 (Ross, 1963). These include recent trauma and surgery, non- Its mode of action is unknown. The administration malignant pulmonary and neurological disease, of large amounts of the potent mineralocorticoid Postgrad Med J: first published as 10.1136/pgmj.53.619.274 on 1 May 1977. Downloaded from

276 Case reports is ineffective in this context (Ross, 1963). GEORGE, M.J., CAPEN, C.C. & PHILLIPS, A.S. (1972) Bio- The need for is illustrated in this case synthesis of vasopressin in vitro and ultrastructure of a high dosage bronchogenic carcinoma. Journal of Clinical Investigation, during the patient's terminal illness, when 0-4 mg 51, 141. daily proved inadequate in preventing continued HAAS, CH., ROSEY, A. & CHOUBRAC, P. (1975) Carcinome du hyponatraemia. thymus et syndrome de Schwartz et Bartter. Nouvelle Presse Medicale, 4, 586. HANTMAN, D., ROSSIER, B., ZOHLMAN, R. & SCHRIER, R. (1973) Rapid correction of hyponatremia in the syndrome Acknowledgments of inappropriate secretion of antidiuretic hormone. We should like to thank Mr D. A. Bailey for permission to Annals of Internal Medicine, 78, 870. report a patient under his care, and Miss C. Ramage, Dr KHOKHAR, A.M., RAMAGE, C.M. & SLATER, J.D.H. (1975) J. D. H. Slater and the Supraregional Assay Service, Middle- Radioimmunoassay of arginine-vasopressin in urine. sex Hospital Medical School, London, for performing the Journal of Endocrinology, 67, 66 P. vasopressin radioimmunoassay. LEBACQ, E. & DELAERC, J. (1965) Hyponatr6mie avec dilution plasmatique, par secretion inadequate de vasopressine, dans un cas de tumeur duod6nale. Revue Medico-Chirur- References gicale des Maladies du Foie, 40, 169. BARTTER, F.C. (1970) The syndrome of inappropriate secre- Ross, E.J. (1963) Hyponatraemic syndromes associated with tion of antidiuretic hormone. Journal of the Royal College carcinoma of the bronchus. Quarterly Journal of Medicine, of Physicians of London, 4, 264. 32, 297. CARTER, J.N., CORCORAN, J.M., EASTMAN, C.J. & LAZARUS, SACKS, S.A., RHODES, D.B., MALKASIAN, D.R. & ROSEN- L. (1974) The effect of severe chronic illness on thyroid BLOOM, A.A. (1975) Prostatic carcinoma producing the function. Lancet, ii, 971. syndrome of inappropriate secretion of antidiuretic hor- CASSILETH, P.A. & TROTMAN, B.W. (1973) Inappropriate mone. Urology, 6, 489. antidiuretic hormone in Hodgkin's disease. American SCHWARTZ, W.B., BENNETT, W., CURELOP, S. & BARTTER, Journal of the Medical Sciences, 265, 233. F.C. (1957) A syndrome of renal sodium loss and hypo- DE SOUSA, R.C. & JENNY, M. (1964) Hyponatr6mie par natremia probably resulting from inappropriate secretion dilution dans un cas de carcinome pancreatique. Schwei- of antidiuretic hormone. American Journal of Medicine, zerische Medizinische Wochenschrift, 94, 930. 23, 529. DE TROYEZ, A. & DEMANET, J-C. (1975) Correction of anti- SVANE, S. (1964) Hypercalcaemia in malignant disease with- diuresis by demeclocycline. New England Journal of out evidence of bone destruction. A case simulating acute by copyright. Medicine, 293, 915. hyperparathyroidism. Acta medica scandinavica, 175, 353. FALCHUK, K.R. (1973) Inappropriate antidiuretic hormone- WHITE, M.G. & FETNER, C.D. (1975) Treatment of in- like syndrome associated with an adrenocortical carcinoma. appropriate secretion of antidiuretic hormone with lithium. American Journal of the Medical Sciences, 266, 393. New England Journal of Medicine, 292, 390.

Postgraduate Medical Journal (May 1977) 53, 276-277. http://pmj.bmj.com/ Non-African Burkitt lymphoma presenting as dysphagia J. R. PITTS A. COWLEY B.Sc., M.R.C.P. M.B., B.S. Department of Medical Oncology, St London Bartholomew's/Hackney Hospitals, on September 30, 2021 by guest. Protected

Summary presented with a 1-month history of progressive Cases of non-African Burkitt lymphoma are rare, but dysphagia and vomiting, associated with weight-loss the clinical manifestations of this and the African type of 5 kg. A barium meal showed hold-up at the cardia are similar. The authors believe that this patient is the of the . Oesophagoscopy showed dilatation first described presenthig with dysphagia without with debris within; no evidence of malignant disease intrinsic gastrointestinal disease. was seen. At laparotomy, a large lobulated retro- peritoneal mass was found, displacing the stomach Case report anteriorly and laterally and compressing the cardia. A 38-year-old Caucasian male was referred to the A biopsy and a gastrostomy were performed and the Department of Medical Oncology, Hackney Hospi- patient transferred to the authors' unit. tal, London, with a large retroperitoneal mass. He On examination he was thin, not clinically anaemic Correspondence: Dr John Pitts, Department of Medical and there was no lymphadenopathy. There was Oncology, St. Bartholomew's Hospital, London ECIA 7BE. mild bilateral ankle oedema. Examination of the