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Postgrad Med J: first published as 10.1136/pgmj.39.449.158 on 1 March 1963. Downloaded from

POSTGRAD. WED. J. (I963), 39, 158

HYPONATRAEMIA WITH CARCINOMA OF THE BRONCHUS J. J. DALY, M.A., M.D.(Cantab.), M.R.C.P. M. A. NELSON, M.B., B.S.(Lond.), F.R.C.S.(Eng.) Lecturer in Medicine Registrar in Orthopeedics D. P. ROSE, M.B., CH.B.(Sheff.) Registrar in Clinical Pathology From the Departments of Medicine, Orthopeedics and Chemical Pathology, The Royal Hospital, Sheffield

SEVERAL previous reports have described the Autopsy findings. An oat-celled carcinoma was occurrence of hyponatrmmia with carcinoma of the present in the left upper lobe main bronchus. There bronchus, and inappropriate secretion of anti- were metastases in the hilar lymph nodes and liver. Both kidneys appeared normal. Histology revealed diuretic hormone was suggested as the mechanism metastases in both adrenals and the pituitary. The accounting for the low serum sodium. (Schwartz, kidneys were normal microscopically. Bennett, Curelop and Bartter 1957, Roberts 1959, Turner and Williams, 1962.) Rees, Rosalki and Maclean (I960), described a case of carcinoma of Comment the bronchus in which theyv. considered renal In the present case a serum sodium level of tubular damage accounted for the low serum IIO mEq./l. was accompanied by a urinary excre- sodium, in the absence of evidence of excessive tion of 42 mEq./24 hours suggesting that failure of secretion of antidiuteric hormone. We wish to renal conservation of sodium contributed to the report a further case of carcinoma of bronchus with hyponatriemia. The possibility that excess secretion hyponatroemia, in which there was evidence of of antidiuretic hormone was a factor cannot how- renal tubular damage. In addition, there was ever be excluded. In addition to the hyponatremia, evidence of adrenal hyperactivity. proximal renal tubular damage was suggestedcopyright. by glycosuria in the presence of a normal fasting blood Case Report sugar, aminoaciduria and hypophosphataEmia. A postman, aged 49, attended the out-patient depart- The association of carcinoma of the bronchus ment in January I962, with a six months' history of intermittent substemal pain occurring at rest. He and adrenal overactivity is well recognized. (Allott was a heavy cigarette smoker. There were no abnormal and Skelton, I960, Bagshawe, ig60a and b.) Our physical signs; a barium-meal examination revealed a patient showed no clinical features of Cushing's hiatus hernia. His symptoms improved with diet and syndrome and the serum potassium was normal. antacids. In June I962 the patient complained of However, the urinary level of was increasingly severe backache radiating to the right higher than those previously reported in cases of thigh. There was loss of lumbar movement and carcinoma of the bronchus with hyponatrxmia. http://pmj.bmj.com/ wasting of the right thigh and calf, with anesthesia over the distribution of segments L2 and L3. He was The case described by Rees and others (I960) admitted to hospital. showed histochemical evidence of adrenal over- Investigations. Chest X-ray: There was pleural cal- activity. Thus the present case more closely cification over the right upper lobe and a shadow at the resembles that described by these workers as left hilum. Hb. 17.0 g./ioo ml., ESR 3 mm./hr. regards both the adrenal and renal abnormalities, Plasma sodium i IO mEq., potassium 4.4 mEq., chloride than the cases in which an abnormality of anti- 8o mEq., and alkali reserve 25 mEq. per litre. Blood diuretic hormone secretion has been postulated as urea 20 mg./ioo ml. Serum calcium 8.6 mg. and on October 2, 2021 by guest. Protected inorganic phosphate i.6 mg./ioo ml., serum alkaline a cause for hyponatrmmia. phosphatase 2I King units. Total serum protein 5.5 g./ioo ml., albumin 4.2 g. globulin 1.3 g. A Summary fasting blood sugar was 92 mg./Ioo ml. The urine contained a moderate amount of albumin A case of hyponatremia with carcinoma of and I% glucose. Microscopy showed numerous red bronchus in a man, aged 49, is described. Glyco- and white cells. Culture was sterile. Urinary sodium suria and aminoaciduria were present. These were 42 mEq., calcium I37 mg., and glucose 3.6 g., all per interpreted as being evidence of impaired renal 24 hours. Urinary : 17-k2tosteroids 20.5 mg., tubular function which probably accounted for the 17-ketogenic steroids 89 mg., and 17-hydroxycorti- costeroids I04 mg. per 24 hours. Chromatography of low serum sodium. The urinary excretion of the urine showed generalized aminoaciduria. corticosteroids was increased but there was no Progress. On the thirteenth hospital day urinary clinical evidence of Cushing's syndrome. retention developed and 24 hours later paraplegia was present with a sensory level at D9-Io. Myelography We would like to express our thanks to Professor showed a block at this level and subsequent laminec- C. H. Stuart-Harris and Mr. F. W. Taylor for per- tomy on June i6 revealed an extensive extra-dural mission to publish details of this case. Our thanks are metastasis. The patient's condition deteriorated rapidly also due to Mr. A. Jefferson for details of the findings and he died on June 29. at operation. Postgrad Med J: first published as 10.1136/pgmj.39.449.158 on 1 March 1963. Downloaded from March I963 DALY, NELSON and ROSE: Hyponatracmia with Carcinoma of the Bronchus 159 REFERENCES ALLOTT, E. N., and SKELTON, M. 0. (I960): Increased Adrenocortical Activity Associated with Malignant Disease, Lancet, ii, 278. BAGSHAWE, K. D. (ig6oa): Hypokalsemia, Carcinoma and Cushing's Syndrome, Ibid., ii, 284. (ig6ob): Hyperfunction of the Adrenal Cortex with Adrenal Metastases, Ibid., ii, 287. REES, J. R., ROSALKI, S. B., and MACLEAN, A. D. W. (I960): Hyponatrsemia and Impaired Renal Tubular Function with Carcinoma of Bronchus, Ibid., ii, IOO5. ROBERTS, H. J. (1959): The Syndrome of Hyponatremia and Renal Sodium Loss Probably Resulting from Inappro- priate Secretion of Antidiuretic Hormone, Ann. intern. Med., 51, 1420. SCHWARTZ, W. B., BENNETT, W., CURELOP, S., and BARTTER, F. C. (1957): A Syndrome of Renal Sodium Loss and Hyponatrxemia Probably Resulting from Inappropriate Secretion of Antidiuretic Hormone, Amer. J. Med., 23, 529. , TASSELL, D., and BARTTER, F. C. (I960): Further Observations on Hyponatrmmia and Renal Sodium Loss Probably Re3ulting from Insppropriate Secretion of Antidiuretic Hormone, New Engl J. Med., 262, 743. TURNER, P., and WILLIAMS, R. (I962): Unexplained Steatorrhoea in the Syndrome of Hyponatreemia and Carcinoma of Bronchus, Brit. med. J7., i, 287.

Clinical Trial

A CLINICAL TRIAL OF FLUPEROLONE: A NEW TOPICAL NAPIER THORNE, M.D., M.R.C.P. copyright. Physician-in-Charge, Skin Departments, Prince of Wales's General Hospital, Mile End Hospital, and St. Andrew's Hospital, Bow.

FOR the evaluation of a new , flupero- patient was unaware that the second preparation lone (P-I742: Methral; Pfizer) a clinical trial was was of a lower concentration than the original. planned in four phases. First, in order to obtain a Chemically this compound is of interest both due clinical impression, ointments of both 0.25% and to inclusion of a fluorine atom, and to the modi- http://pmj.bmj.com/ i.o% and'spray pack preparations, were used for the fication of one of the side chains by the introduction treatment of a variety of commonly occurring of a methyl grouping at position C21. The structure dermatoses. Secondly, following encouraging of fluperolone can be described as 2I-methyl-g9 results from this pilot trial and favourable reports flouro- (Fig. I). from another centre (Sneddon, I962), a double blind comparative trial was undertaken with prepara- tions containing either 0.25% fluperolone or I.o% O CH . Both were of identical appearance ,, I 3 and consistency, and were dispensed in a water H C-C-O-CH, on October 2, 2021 by guest. Protected miscible base. In this phase of the trial. patients 3 1 were given, in a blind, random manner, one of the C =0 two preparations, but at the first follow-up visit after one week, the preparation was changed. The /'OH randomization was such that approximately equal HO numbers of patients commenced therapy with both preparations. The third phase of this trial was also F a double blind study, planned in an identical manner, but comparing o. i % fluperolone and i .o% hydrocortisone. Lastly, in the fourth phase, patients with various types of eczema were treated with o.i% fluperolone but at the first follow-up visit the preparation was changed to o.oi % flupero- lone, to see whether this low concentration would be o / adequate to maintain the improvement observed FIG. I.-Fluperolone: note inclusion of fluorine atom during treatment with the o.i% preparation. The at Cg and methyl group at position C21.