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SERUM-PROLACTIN IN PATIENTS RECEIVING CHRONIC ORAL CIMETIDINE
881 shown that human skin contains the histamine-degrading enzyme N-methyltransferase.4 Enzymic histamine degradation may regulate cutaneous hypersensitivity reactions,5 and we have demonstrated the inhibition of N-methyltransferase by cimetidine.6 The augmentation of delayed hypersensitivity reactions in skin may thus be due to reduced decay of histamine activity. Histamine plays a central but complex role in allergic skin reactions and its effects can be modified by cimetidine at a number of different points. I agree with Avella et al. that clinicians must be alert to the possible immunological consequences of use of this drug. Institute of Dermatology, London E9 6BX
result from an antiandrogenic effect of evidence that chronic oral cimetidine sustained hyperprolactinsemia like that caused by
prolactinocmia but the
drug. 13
causes
may
We found
no
chronic
phenothiazines. 14 Recognised causes of prolactin hyperM.E.N. i, should be looked for in patients on cimetidine who show hyperprolactinsemia.
secretion, including
Metabolic Diseases Branch, and Section on Gastroenterology, Digestive Diseases Branch, National Institute of Arthritis, Metabolism, and Digestive Diseases, National Institutes of Health, Bethesda, Maryland 20014, U.S.A.
A. M. SPIEGEL R. LOPATIN S. PEIKIN D. MCCARTHY
MALCOLM W. GREAVES
ASSOCIATION BETWEEN PULMONARY TUBERCULOSIS AND BRONCHIAL CARCINOMA SERUM-PROLACTIN IN PATIENTS RECEIVING CHRONIC ORAL CIMETIDINE
S:R,—The development of gynaecomastia in men and galactorrhrea in women taking cimetidine7-9 may be due to a cimetidine-induced increase in serum-prolactin 8-4We report here the effects of chronic oral cimetidine therapy on serum-prolactin in seven patients with Zollinger-Ellison (z.E.) syndrome. Serum-prolactin was measured by radioimmunoassay5 (normal range, 2-27 ng/ml men, 2-37 ng/ml women) in samples taken before therapy and in samples taken when the patients had been on cimetidine (1.2-2.4 g orally per day) for at least 6 months. Samples were collected at 8 A.M. in the basal state after overnight fast. SERUM-P.R.L. BEFORE AND DURING TREATMENT WITH CIMETIDINE IN ZOLLINGER-ELLISON SYNDROME
SIR,-Dr Edlin (March 25, p. 650) maintains that pulmonary tuberculosis and carcinoma of the bronchus are negatively associated, giving references from 1929 and 1932. With changes in the incidence and mortality of tuberculosis this is no longer true. Now it is clear that tuberculosis and bronchial carcinoma coexist commonly, and probably more often than expected by chance. This association is probable rather than proved because the exact frequency with which active tuberculosis occurs with lung cancer is not known. There are, however, some indications: Springett showed that men aged 35 and over, diagnosed as having tuberculosis in 1959, have a higher than expected death-rate from bronchial carcinoma.1 These diseases might be expected to coincide in a few cases by chance, since both are predominantly killers of old men who smoke.2,3 One explanation for an increase in the frequency of coincidence might be the reactivation of pulmonary tuberculosis by cancer of the bronchus.4 Department of Pathology, Medical School, Birmingham B15 2TJ
A. J. HOWIE
LEVEEN SHUNTS
*All patients received cimetidine for at least 6 months before repeat determination except for patient 3 who received cimetidine for 2 weeks.
Serum-prolactin was raised in female patients (nos. 3 and 4) before therapy, and cimetidine did not greatly alter these levels (see table); in both patients z.E. syndrome was part of the multiple endocrine neoplasia type i complex (M.E.N. I) with associated hyperparathyroidism. Neither had galactorrhoea. In five other patients, including no. 1 and no. 2 with M.E.N. i, serumprolactin was normal before and during cimetidine therapy. One male patient (no. 6) complained of breast tenderness after 3 months of cimetidine therapy.
SIR,-Our experiences with the LeVeen shunt in patients with intractable malignant ascites parallel those of Mr Arnot and Mr White (March 4, p. 509) and of Pollock.’ With local anxsthesia in all but one patient, we have observed dramatic relief of the tense ascites and associated symptoms in six of eight patients with various malignancies. Palliation continued throughout the remaining weeks and months of life. The average weight loss was 7 kg. Two patients had a necropsy. In neither was histological evidence of malignant implantation in the superior vena cava found. Two patients did not benefit. One had abnormal clotting functions before surgery and a severe coagulation disorder in the early postoperative period. She died of fulminant hepatic failure. The second failure seemed to be due to obstruction of the intraperitoneal shunt ports by clumps of malignant cells. Although the LeVeen shunt does not affect the course of the disease it may relieve the patient of the unpleasant symptoms of massive ascites.
Pituitary involvement, including prolactin hypersecretion, has been previously reported in the M.E.N. i syndrome6 and is the most likely explanation for the increased serum-prolactin in patients 3 and 4. Gynmcomastia and breast soreness in men receiving cimetidine7.8 have not been accompanied by hyper4. 5.
Francis, D., Greaves, M. W., Yamamoto, S. Br. J. Pharmac. 1977, 60, 583. Yamamoto, S., Francis, D., Greaves, M. W. Clin. exp. Immun. 1976, 26,
583. 6. Corbett, J. R., Francis, D., Greaves, M. W. Unpublished. 7. Hall, W. H. New Engl. J. Med. 1976, 295, 841. 8. Delle Fave, G., and others. Lancet, 1977, i, 1319. 9. Bateson, M. C., Browning, M. C. K., Maconnachie, A. ibid. ii, 247. 10. Carlson, H. E., Ippoliti, A. F. J. clin. Endocr. 1977, 45, 367. 11. Rogol, A. D., Rosen, S. W. ibid. 1974, 38, 714. 12. Clinicopathologic Conference. Am. J. Med. 1974, 57, 611.
of Surgery,
Department Ohio State University, Columbus, Ohio 43210,
13. Leslie, G. B.,
posium
on
U.S.A.
Walker, T. Histamine
KENNETH A. KUDSK TIMOTHY C. FABIAN D. J. T. WEBSTER JOHN P. MINTON
F. in Proceedings of the Second International SymH2 Receptor Antagonists (edited by W. L. Burland
and M. A. Simkins); p. 24. Amsterdam, 1977. Tolis, G., Somma, M., Van Campenhout, J., Friesen, A. Am. J. Obstet. Gynec. 1974, 118, 91. 1. Springett, V. H. Tubercle, 1971, 52, 73. 2. Mortality Statistics. Office of Population, Censuses and Surveys, 1975. 3. Doll, R., Peto, R. Br. med. J. 1976, ii, 1525. 4. Snider, G. L., Placik, B. Am. Rev. resp. Dis. 1969, 99, 229. 5. Pollock, A. V., Br. J. Surg. 1975, 62, 104.
14.
result from an antiandrogenic effect of evidence that chronic oral cimetidine sustained hyperprolactinsemia like that caused by
prolactinocmia but the
drug. 13
causes
may
We found
no
chronic
phenothiazines. 14 Recognised causes of prolactin hyperM.E.N. i, should be looked for in patients on cimetidine who show hyperprolactinsemia.
secretion, including
Metabolic Diseases Branch, and Section on Gastroenterology, Digestive Diseases Branch, National Institute of Arthritis, Metabolism, and Digestive Diseases, National Institutes of Health, Bethesda, Maryland 20014, U.S.A.
A. M. SPIEGEL R. LOPATIN S. PEIKIN D. MCCARTHY
MALCOLM W. GREAVES
ASSOCIATION BETWEEN PULMONARY TUBERCULOSIS AND BRONCHIAL CARCINOMA SERUM-PROLACTIN IN PATIENTS RECEIVING CHRONIC ORAL CIMETIDINE
S:R,—The development of gynaecomastia in men and galactorrhrea in women taking cimetidine7-9 may be due to a cimetidine-induced increase in serum-prolactin 8-4We report here the effects of chronic oral cimetidine therapy on serum-prolactin in seven patients with Zollinger-Ellison (z.E.) syndrome. Serum-prolactin was measured by radioimmunoassay5 (normal range, 2-27 ng/ml men, 2-37 ng/ml women) in samples taken before therapy and in samples taken when the patients had been on cimetidine (1.2-2.4 g orally per day) for at least 6 months. Samples were collected at 8 A.M. in the basal state after overnight fast. SERUM-P.R.L. BEFORE AND DURING TREATMENT WITH CIMETIDINE IN ZOLLINGER-ELLISON SYNDROME
SIR,-Dr Edlin (March 25, p. 650) maintains that pulmonary tuberculosis and carcinoma of the bronchus are negatively associated, giving references from 1929 and 1932. With changes in the incidence and mortality of tuberculosis this is no longer true. Now it is clear that tuberculosis and bronchial carcinoma coexist commonly, and probably more often than expected by chance. This association is probable rather than proved because the exact frequency with which active tuberculosis occurs with lung cancer is not known. There are, however, some indications: Springett showed that men aged 35 and over, diagnosed as having tuberculosis in 1959, have a higher than expected death-rate from bronchial carcinoma.1 These diseases might be expected to coincide in a few cases by chance, since both are predominantly killers of old men who smoke.2,3 One explanation for an increase in the frequency of coincidence might be the reactivation of pulmonary tuberculosis by cancer of the bronchus.4 Department of Pathology, Medical School, Birmingham B15 2TJ
A. J. HOWIE
LEVEEN SHUNTS
*All patients received cimetidine for at least 6 months before repeat determination except for patient 3 who received cimetidine for 2 weeks.
Serum-prolactin was raised in female patients (nos. 3 and 4) before therapy, and cimetidine did not greatly alter these levels (see table); in both patients z.E. syndrome was part of the multiple endocrine neoplasia type i complex (M.E.N. I) with associated hyperparathyroidism. Neither had galactorrhoea. In five other patients, including no. 1 and no. 2 with M.E.N. i, serumprolactin was normal before and during cimetidine therapy. One male patient (no. 6) complained of breast tenderness after 3 months of cimetidine therapy.
SIR,-Our experiences with the LeVeen shunt in patients with intractable malignant ascites parallel those of Mr Arnot and Mr White (March 4, p. 509) and of Pollock.’ With local anxsthesia in all but one patient, we have observed dramatic relief of the tense ascites and associated symptoms in six of eight patients with various malignancies. Palliation continued throughout the remaining weeks and months of life. The average weight loss was 7 kg. Two patients had a necropsy. In neither was histological evidence of malignant implantation in the superior vena cava found. Two patients did not benefit. One had abnormal clotting functions before surgery and a severe coagulation disorder in the early postoperative period. She died of fulminant hepatic failure. The second failure seemed to be due to obstruction of the intraperitoneal shunt ports by clumps of malignant cells. Although the LeVeen shunt does not affect the course of the disease it may relieve the patient of the unpleasant symptoms of massive ascites.
Pituitary involvement, including prolactin hypersecretion, has been previously reported in the M.E.N. i syndrome6 and is the most likely explanation for the increased serum-prolactin in patients 3 and 4. Gynmcomastia and breast soreness in men receiving cimetidine7.8 have not been accompanied by hyper4. 5.
Francis, D., Greaves, M. W., Yamamoto, S. Br. J. Pharmac. 1977, 60, 583. Yamamoto, S., Francis, D., Greaves, M. W. Clin. exp. Immun. 1976, 26,
583. 6. Corbett, J. R., Francis, D., Greaves, M. W. Unpublished. 7. Hall, W. H. New Engl. J. Med. 1976, 295, 841. 8. Delle Fave, G., and others. Lancet, 1977, i, 1319. 9. Bateson, M. C., Browning, M. C. K., Maconnachie, A. ibid. ii, 247. 10. Carlson, H. E., Ippoliti, A. F. J. clin. Endocr. 1977, 45, 367. 11. Rogol, A. D., Rosen, S. W. ibid. 1974, 38, 714. 12. Clinicopathologic Conference. Am. J. Med. 1974, 57, 611.
of Surgery,
Department Ohio State University, Columbus, Ohio 43210,
13. Leslie, G. B.,
posium
on
U.S.A.
Walker, T. Histamine
KENNETH A. KUDSK TIMOTHY C. FABIAN D. J. T. WEBSTER JOHN P. MINTON
F. in Proceedings of the Second International SymH2 Receptor Antagonists (edited by W. L. Burland
and M. A. Simkins); p. 24. Amsterdam, 1977. Tolis, G., Somma, M., Van Campenhout, J., Friesen, A. Am. J. Obstet. Gynec. 1974, 118, 91. 1. Springett, V. H. Tubercle, 1971, 52, 73. 2. Mortality Statistics. Office of Population, Censuses and Surveys, 1975. 3. Doll, R., Peto, R. Br. med. J. 1976, ii, 1525. 4. Snider, G. L., Placik, B. Am. Rev. resp. Dis. 1969, 99, 229. 5. Pollock, A. V., Br. J. Surg. 1975, 62, 104.
14.