1121

respectively) but since myxoedema for less than 1 % of cases even at a special accounts thyroid clinic such as ours, we decided to concentrate on Hashimoto’s thyroiditis. Our study revealed a higher incidence of breast cancer for the index group than expected, so ’we next compared this incidence with that for different populations (table ill). The incidence of breast cancer was 126.8 per 100 000 females aged over thirty for the Hashimoto’s thyroiditis study, and 23.4 per 100 000

thyroid

status,

population covered by the Osaka tumour registry.14 This suggests that patients with Hashimoto’s thyroiditis in Japan are at 5.4 times greater risk of for the

than the general population. Also the incidence-rate of breast cancer for Hashimoto’s thyroiditis was almost the same as that for the U.S. general population such as Connecticut or Alameda County of California, though the rate for England was 101.4 per 100000. N. M. has lately been working on a similar project in collaboration with Dr L. T. Kurland of the Mayo Clinic. This study, on residents of Rochester, Minnesota, for the years 1935-74, is still in progress but it seems likely that the incidence of breast cancer for patients with Hashimoto’s thyroiditis is also higher than that for general population.16 In 1970, there were 409 new cases of breast cancer in women aged over thirty in Osaka. 14 Using prevalence figures for Hashimoto’s thyroiditis from our work in the Nagano prefecture,17 8852 women over the age of thirty in Osaka in 1970 would be expected to have Hashimoto’s thyroiditis. Table iv shows that there might be about 12 cases of breast cancer associated with Hashimoto’s thyroiditis in the population out of 409 cases altogether in 1970. In other words some 3% of breast cancer in Japan might be associated with or caused by Hashimoto’s thyroiditis. breast

cancer

On the other hand, we found no cases of breast in women with myxoedema or hyperthyroidism. We might have expected that severe hypothyroid status (myxcedema) would also make some contribution to breast cancer. However the incidence of breast cancer was not increased in myxoedema, though the numbers were small. This finding may support the suggestion that growth of breast cancer is inhibited in severe hypothyroidism due to the accompanying abnormalities in growth hormone and oestrogen secretion, two hormones that are essential for breast-cancer growth. IS It seems then that only mild or subclinical hypothyroidism such as Hashimoto’s thyroiditis is of xtiological importance in breast cancer. The incidence of breast cancer in Japan is almost the lowest among the developed countries in the world;’3 and Mr I. Mittra of Guy’s Hospital, London, has been measuring thyroid autoantibodies in large groups of healthy British and Japanese women, in collaboration with Dr S. Kumaoka of Japan. They have found that microsomal antibodies are four times more common, and thyroglobulin antibodies twice as common, in the British women compared with the Japanese.18 This further suggests that mild hypothyroidism such as Hashimoto’s thyroiditis may be a risk factor in breast cancer because patients with cancer

Hashimoto’s thyroiditis have a higher incidence of thyroid autoantibodies. The control group with benign nodular goitre also showed some cases of breast cancer, though the incidence was not significantly higher than expected. It is our impression that many patients with benign nodular goitre may have Hashimoto’s thyroiditis in tissue surrounding thyroid nodules pathologically. This is N. M.’s impression, based on a review of case records at the Mayo Clinic. If this is confirmed then benign nodular goitre would also be a risk factor ,

for breast

cancer.

The study was supported by the cancer research grants of the Japanese Ministry of Health and Welfare, 1974 and 1975. We thank the following doctors of the Itoh Clinic and Hospital, Tokyo, who assisted us in data collection in the early phase of the project: Dr Y. Nishikawa, Dr T. Mimura, Dr N. Momotani, and Dr Y. Ban. We also thank Mrs Y. Tanaka and Mrs K. Niihashi for their assistance in follow-up procedures. Requests for reprints should be addressed to N.M., School of Health Sciences, University of Tokyo, Hongo, Bunkyo-ku,

Tokyo, Japan

113.

REFERENCES 1. Spencer, J. G. C. Br. J. Cancer, 1954, 8, 393. 2. Lancet, 1974, i, 908. 3. Reppert, R. W.J. Michigan med. Soc. 1952, 51, 1315. 4. Sommers, S. C. Lab. Invest. 1955, 4, 160. 5. Eskin, B. A. Trans. N. Y. Acad. Sci. 1970, 32, 911. 6. Ellerker, A. G. Med. Press, 1956, 235, 280. 7. Reeve, T. S., Hales, I. B., Rundle, F. F., Myhill, J., Croydon, M. Lancet, 1961, i, 632. 8. Cappelli, L., Margottini, M. Acta Un. int. Cancr. 1964, 20, 1493. 9. Stoll, B. A. Cancer, 1965, 18, 1431. 10. Schottenfeld, D.J. chron. Dis. 1968, 21, 303. 11. Moossa, A. R., Price Evans, D. A., Brewer, A. C. Ann. R. Coll. Surg. Engl. 1973, 53, 178. 12. Liechty, R. D., Hodges, R. E., Burket, J.J. Am. med. Ass. 1963, 183, 30. 13. Doll, R., Muir, C., Waterhouse, J. (editors) Cancer Incidence in Five Continents. Berlin, 1970. 14. Osaka Medical Association, Department of Health, Osaka, and Center for Adult Diseases, Osaka. The Tumour Registry in Osaka; vol. XIX. Osaka, 1973. 15. Shibusawa, K. Clin. Gynec. Obstet., Tokyo 1962, 16, 721. 16. Maruchi, N., Kurland, L. T. Unpublished. 17. Maruchi, N., Furihata, R., Makiuchi, M. Igaku no Ayumi (in Japanese), 1974, 88, 20. 18. Mittra, I. Personal communication.

GASTRIC FUNCTION IN CHRONIC RENAL FAILURE EFFECTS OF MAINTENANCE HÆMODIALYSIS

J.

W. K. STEWART K. G. WORMSI EY

B. MCCONNELL

B.

THJODLEIFSSON Departments of Medicine and Therapeutics, University of Dundee

40 patients with chronic renal failure have been studied in order to determine why some patients with azotæmia have previously been reported to secrete abnormally large amounts of acid and some to secrete very little. 15 of the 40 patients were undergoing regular hæmodialysis, while the remaining 25 patients had not been so treated. 10 of the 25 nondialysed patients had much-impaired capacity to secrete acid. The impaired gastric secretory capacity was corrected and became abnormally great after some months of regular hæmodialysis in 4 patients. Regular hæmodialysis, by removing factors responsible for the gastric

Summary

1122

mucosal

damage, permits manifestation ing gastric hypersecretory state.

of

an

underly-

Introduction

RECENT investigation of the factors underlying the high incidence of duodenal ulceration in patients with chronic renal failure undergoing maintainance haemodialysis has confirmed a marked tendency to gastric hypersecretion,’2 although earlier studies had indicated a high incidence of gastric secretory impairment in patients with chronic renal failure.34 In an attempt to resolve these differences, we have sought to correlate gastric-acid secretory capacity with differing degrees of renal failure and have also examined the long-term effects of maintenance haemodialysis on gastric-acid secretion. Materials and Methods Patients 40 patients with chronic renal failure gave informed consent the study. 25 of these patients (6 glomerulonephritis, 6 chronic pyelonephritis, 2 hypertension, 2 renal calculus disease, 1 granulomatous renal disease, 1 polycystic disease, 7 undetermined causation) had not undergone dialysis at the time of study. These patients were classified in three subgroups, according to the plasma concentration of creatinine, as follows : to

(a) Plasma-creatinine 180-440 mot/1 (2-5 mg/100 ml); (b) Plasma-creatinine 440-880 f!moVl (5-10 mg/100 ml); (c) Plasma-creatinine greater than 880 {imot/1 (> 10 mg/100 ml). 4 of the patients with chronic renal failure subsequently underwent secretory studies on two further occasions, after 5 and 9 months of regular dialysis. The other 15 patients (8 glomerulonephritis, 4 chronic pyelonephritis, 2 analgesic nephropathy, 1 polycystic kidney) had received regular dialysis at the time of study for periods ranging from 3 months to nearly 6 years. The haemodialysis treatment comprised an average of 17 hours per week in two sessions of equal length with extracorporeal ’Ex-03’ disposable coil dialysers.

Secretory Tests After an overnight fast, a modified nasogastric (Ryle’s) tube was sited under radiological control with its tip in the antrum. Residual gastric contents were aspirated and discarded. Basal gastric secretion was aspirated continuously for 60 minutes. Each patient then received pentagastrin according to one of the two schedules which have been shown5-’ to give equivalent measures of gastric secretory capacity:

Fig. 1-Sqcretory data from patients with non-dialysed compared with patients receiving regular haemodialysis.

renal failure

Each point represents results from one individual. Closed symbols renal indicate patients in the three subgroups (see text) of failure (c.R.F.); open circles depict results from patients receiving regular haemodialysis (D).

non-dialysed

secretory responses to the administration of pentagastrin, multiplied by three to give acid outputs in mmol/hour. Peak acid concentration refers to the maximal acid concentration attained during the response to pentagastrin. The secretory data from the three sub-groups of chronic renal failure and from patients on haemodialysis have been compared by means of the Mann-Whitney "U" test.

Analytical Methods The concentration of acid in the gastric aspirate was measured by titration with 0-11 moO sodium hydroxide to pH 70 using an automatic titrator (Radiometer, Copenhagen). The concentration of creatinine in plasma was measured by the alkaline picrate method.

Results Basal Secretion There was no significant correlation between the severity of the renal damage, as assessed by the concentration of plasma-creatinine and basal output of acid,

(1) In 20 patients (9 chronic renal failure; 11maintenance haemodialysis) pentagastrin was given by subcutaneous injection in a dose of 6 Ilg/kg body-weight, as described previously.6 Gastnc contents were aspirated for 60 minutes in 10-minute batches. This method of giving pentagastrin was used particularly when intravenous administration in sodium-chloride solution

was

clinically undesirable.

(2) 24 patients (16 chronic renal failure; 8 haemodialysis) received pentagastrin (3’24 jig/kg/hour) by continuous intravenous tnfusion in z 15 mol/1 sodium chloride.

patients with chronic renal failure (subgroup c) substarted haemodialysis and were retested at 5 and 9 months after the beginning of regular dialysis. 4 of the

sequently

Fig. 2-Effect

Calculations To permit comparison with other reports, outputs of acid have been expressed as the highest consecutive two 10-minute

of

regular haemodialysis on

basal and stimulated acid

sec-

retion.

Each point represents mean (+ s.n.) of results from 4 patienis before dialysis (predialysls) and after 5 months’ (5/12) and 9 month"

(9/12) regular haemodiatysis.

1123 since the values of acid output were not significantly different for the three subgroups of patients with chronic renal failure not undergoing dialysis (fig. 1). The basal acid secretions of the non-dialysed patients taken as one group were less [range 0-22.0 mmol/h and median value 1.8 mmol/h] than those of the patients receiving haemodialysis (range 0.3-23.5mmol/h; median 4.55 mmol/h) (fig. 1) but the difference did not reach levels of statistical significance.

Response to Pentagastrin The three subgroups of patients with chronic renal failure not receiving dialysis had peak acid concentrations and outputs which were not significantly different among the subgroups. Nearly half the patients with chronic renal failure had peak acid concentrations of less than 100 mmol/1 (fig. 1). The values of peak acid concentration (range 0-145 mmol/l; median 121 mmol/1 of the combined subgroups of patients with chronic renal failure were significantly less than the values (range 109-148 mmol/1; median 128 mmol/1) of the patients receiving haemodialysis (p

Gastric function in chronic renal failure. Effects of maintenance haemodialysis.

1121 respectively) but since myxoedema for less than 1 % of cases even at a special accounts thyroid clinic such as ours, we decided to concentrate o...
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