- Email: [email protected]
DOES MALABSORPTION OF VITAMIN B12 OCCUR IN CHRONIC PANCREATITIS ?
241
Adiposity is not necessarily directly related to overweight, but Billewicz et aU argue that, of the indices of adiposity commonly used, the weight/ standard weight ratio is the best index. We have expressed the weights of our patients similarly, as a percentage of the predicted mean weight for the corresponding age, height, and sex. Whilst our results show no evidence of overweight in the older age-groups, there is a tendency to overweight in the younger patients which is most noticeable in the 25-34 age-group. In the Framingham study, of the patients in whom gallstones developed during the period of the survey, the 40-49 age-group was significantly heavier than the control population. Of the symptoms experienced by patients with gallstones, pain is the most dramatic, being severe, French and Robb,8 protracted, and persistent. analysed fifty consecutive cases of gallstone colic and concluded that intermittent pain, as implied by the word colic, is rare. Although the epigastrium and the right hypochondrium were the commonest sites of pain, pain in the supracostal areas was common. No doubt some of the unusual pain sites are due to the patient’s inability to localise the pain; this is more probable if the nervous pathways involved are autonomic, as in distension of the biliary tract. Conversely, one would expect local peritonitis in association with cholecystitis to be accurately localised by the patient. On history alone, however, like French and Robb,8 we found that the site and nature of the pain did not indicate its precise cause. The apparent relief of pain by alkalis in almost a third of our patients is not understood but is a characteristic not exclusive to the pain of peptic ulcers. Symptoms of dyspepsia are not so easily evaluated. Price,9who interviewed a random sample of the female population in a general practice, found no difference in dyspeptic symptoms amongst females with normal or abnormal cholecystograms. In our patients, however, the symptoms of dyspepsia were usually relieved after cholecystectomy, and this agrees with the findings of Rhind and Watson.10 The two Whilst views are not necessarily contradictory. accepting that dyspepsia is common amongst women and that some may have coincidental gallstones which do not cause symptoms, this does not mean that patients who have dyspepsia as a result of biliary obstruction and inflammation will not have it relieved by cholecystectomy along with their pain. Heartburn was one of the more common dyspeptic symptoms and was usually relieved by operation. Southam 11 also found that patients with a positive cesophageal-perfusion test (i.e., patients who had symptoms of reflux with oesophageal perfusion by 0.1N hydrochloric acid) had a negative perfusionafter cholecystectomy. Tenderness in the right hypochondrium and epigastrium in patients with gallstones, with local signs of peritonitis, is expected if there is cholecystitis. Even between attacks of pain there may be an illdefined mass in the right hypochondrium indicating a distended gallbladder, a mucocele, or adherent omentum. Tests for hyperxsthesia are of doubtful in and our experience Boas’ sign is of no use. value, test
Only about a third of patients with a history of jaundice were subsequently found to have stones in the common bileduct, and over a third of the patients with common-duct stones gave no history of jaundice and had normal liver-function tests. We thank Mr. W. F. Nicholson for permission patients under his care. Requests for reprints should be addressed to N. K.
to
study
REFERENCES B. G. A. Gallstones and their
1.
Moynihan,
4.
1966, 19, 273. Glenn, F., McSherry, C. K. Surgery Gynec. Obstet. 1968, 127,
Surgical Treatment; p. 116. London, 1905. 2. Montegriffo, V. E. Ann. hum. Genet. 1968, 31, 389. 3. Friedman, G. D., Kannel, W. B., Dawber, T. R. J. chron. Dis. 1067. 5. Horn, G. Br. med. J. 1956, ii, 732. 6. Nix, J. T. Am. J. Gastroent., N.Y. 1965, 43, 208. 7. Billewicz, W. Z., Kemsley, W. F. F., Thomson, A. M. prev. soc. Med. 1962, 16, 183. 8. French, E. B., Robb, W. A. T. Br. med. J. 1963, ii, 135. 9. Price, W. H. ibid. p. 138. 10. Rhind, J. A., Watson, L. ibid. 1968, i, 32. 11. Southam, J. A. Br. J. Surg. 1969, 56, 671.
Br. J.
DOES MALABSORPTION OF VITAMIN B12 OCCUR IN CHRONIC PANCREATITIS ?
J. T. HENDERSON* J. D. SIMPSON R. R. G. WARWICK D. J. C. SHEARMAN Gastro-Intestinal Section of University Department Therapeutics,
of Department of Medical Physics, Royal Infirmary, Edinburgh EH3 9YW and
Seven patients with chronic pancreaSummary titis underwent vitamin-B12 absorption tests by the whole-body counting method. Four of the seven patients malabsorbed vitamin B12 in the fasting state, but absorption was normal when food was given. This may explain reports of vitamin-B12 malabsorption in chronic pancreatitis despite the rarity of vitamin-B12 deficiency. One patient with malabsorption in the fasting state had normal absorption when sodium bicarbonate or normal pancreatic juice was given. Introduction
MALABSORPTION of vitamin Bis was demonstrated by Mclntyre et al.l in four out of five subjects with chronic exocrine pancreatic insufficiency. This was not corrected by administration of exogenous intrinsic factor. Similar findings have since been reported by others. 2-7 However, the mechanism of vitamin-B12 malabsorption in subjects with chronic exocrine pancreatic insufficiency is still in dispute. Despite these reports of vitamin-BlI! malabsorption, deficiency of vitamin BlI! is very rare. Evans and Wollaeger4 mention two subjects with chronic exocrine pancreatic insufficiency, vitamin-Biz malabsorption, and mild macrocytic anaemia which responded to parenteral vitamin B12. LeBauer et al.report a single case of chronic exocrine pancreatic insufficiency, severe megaloblastic anaemia, and vitamin-B12 mal*
Present address: Department of Medicine, University of Edinburgh, Royal Infirmary, Edinburgh EH3 9YW.
242 TABLE I-CLINICAL DETAILS OF PATIENTS WITH CHRONIC PANCREATITIS
tained less than 0-02 (1.g. vitamin BI.2- Pancreatic supplements were not allowed for 24 hours before any test. Retention of cobalt-58 at 7 days of 30% or more is regarded as normal. Patient no. 1 was basally achlorhydric, but produced 10 meq. of acid in the first hour after pentagastrin in an intramuscular dose of 6 (1.g. per kg. The following separate studies were performed on this subject:
(1) Gastric acid secretion was stimulated by pentagastrin kg. intramuscularly 30 minutes before and 30 minutes after drinking 5"Co-labelled cyanocobalamin. (2) 135 ml. of pancreatic juice from a subject with normal pancreatic function was administered through a fine tube, the tip of which lay in the second part of the duodenum. The juice was given, at a rate of 1-5 ml. per minute, for 30 minutes before and for 1 hour after drinking s8Go-labelled cyanocobalamin. (3) Twenty milliequivalents of sodium bicarbonate in 200 ml. of water were administered by mouth over a period of 2 hours starting just before the 68Co-labelled cyanocobalamin 6 vg. per
*
t
Normal values: (a) volume >2’0 bonate conc. > 75 meq. per > 200 units per ml. Steatorrhoea > 7 g. fat per day.
ml. per kg.; (b) maximum bicarlitre; (c) maximum trypsin activity
absorption, but the ansemia may have resulted from folic-acid deficiency. All previous studies have assessed vitamin-Biz absorption using the Schilling test, where absorption is measured in the fasting state. We report here a comparison of vitamin-B12 absorption fasting and with food in subjects with chronic exocrine pancreatic insufficiency. Patients and Methods
Patients The clinical details of seven patients with chronic are shown in table I. No other cause for steatorrhcea could be identified in any patient. Pancreatic function tests were carried out using a Dreiling doublelumen tube.8 The pancreas was stimulated in patients 2 and 5 by intravenous secretin (Boots) in a dose of 3 units per kg. body-weight. In patients 1, 4, and 6 secretin (Karolinska) 1 unit per kg. was used. In patients 3 and 7 pancreatic function tests were not performed. In patient 3 a reliable pancreatic function test could not be performed because of a Polya partial gastrectomy. He presented with severe Steatorrhoea which improved with pancreatic supplements. In patient 7 the diagnosis was based on a history of recurrent upper abdominal pain, severe pancreatic calcification, and the response of Steatorrhoea to pancreatic
pancreatitis
supplements. Vitamin-B12 absorption was measured using a wholebody counter of shadow shield design.D,lO Each subject drank 0-5 .g. of cyanocobalamin labelled with 1 c. of cobalt-58 with 100 ml. of
water
after
a
days later. As
12-hour fast.
after this test was performed, but on this occasion the 58Co-labelled cyanocobalamin in 100 ml. of water was drunk in sips while the subject ate a vitamin-B12free meal. By Euglena gracilis assay, the meal itself conTABLE
drunk.
Results
Table 11 shows that malabsorption of vitamin B12 was found in four of the seven patients when assessed in the fasting state. In all four of these patients absorption of vitamin B12 was normal when a vitamin-B12free meal was eaten together with the oral dose of 68Co-labelled cyanocobalamin. In the remaining three patients absorption was normal in both tests. In table ill the results of the more detailed studies in patient 1 can be seen. Malabsorption of vitamin B12 TABLE III-EFFECT OF VARYING TEST CONDITIONS ON ABSORPTION IN PATIENT NO. 1
VITAMIN-Big
present in the fasting state with or without pentagastrin. Normal absorption occurred with food and when either pancreatic juice or sodium bicarbonate was administered in the fasting state.
was
Methods
Absorption was measured test as possible, a further
was
7
soon
II-VITAMIN-Bn ABSORPTION IN PATIENTS WITH CHRONIC EXOCRINE PANCREATIC INSUFFICIENCY: COMPARISON OF ABSORPTION FASTING AND WITH VITAMIN-B12-FREE MEAL
Discussion
Whole-body counting provides
a
quantitative
method of assessing vitamin-B12 absorption which does not depend on the collection of urine or faeces.9-12I The presence of retained but unabsorbed radioactivity can be excluded by profile scanning.13 There is a poor correlation between successive tests of vitamin-B12 absorption in the fasting state, but this improves when the tests are performed with food," probably because the latter test is more physiological. In this study we have confirmed that, in subjects with chronic exocrine pancreatic insufficiency, vitaminB12 absorption, measured in the fasting subject, may be depressed. However, we have demonstrated that vitamin-B12 absorption is normal when a vitamin-Bnfree meal is taken with the 5"Co-labellcd cyanocobalamin. Although it has previously been noted that absorption of 58Co-labelled cyanocobalamin is greater
243
when it is taken with a meal than when fasting,14 the increase in absorption in such circumstances is small compared with the large increase found in patients 1-4 in this study. The finding of normal absorption in non-fasting tests appears to offer a more plausible explanation for the absence of vitamin-B12 deficiency in subjects with chronic exocrine pancreatic insufficiency than the finding by Toskes et al. of a considerable variation in the ability to absorb vitamin B12 over a period of several months. In the one subject where several absorption studies were performed, the results suggest the possibility that a low intraluminal small-intestinal pH affects vitamin-B12 absorption. During fasting with or without pentagastrin stimulation, malabsorption of vitamin B12 was found. However, absorption was normal in fasting tests when either sodium bicarbonate or pancreatic juice was administered, and when food was given with the test. Such a conclusion is supported by the finding of vitamin-Bn malabsorption in the Zollinger-Ellison syndrome first reported by Shimoda et al.15 and subsequently by Shum et al. 16 The former workers reported reversal of vitamin-Bus malabsorption when the intraduodenal pH was maintained at 7. The intraduodenal pH in fasting subjects with chronic exocrine pancreatic insufficiency is lower than normal. 3, 17 However, after food the pH of the upper small intestine,18 as distinct from the duodenal bulb, 19,20 is similar in normal subjects and subjects with chronic exocrine pancreatic insufficiency. Thus the low pH in the duodenum 3,17 might be the cause of vitamin-B12 malabsorption in the fasting state, but the mechanism is not clear because this low pH will not affect significantly vitamin-B12intrinsic-factor binding. 21-23 Uptake of vitamin-B12intrinsic-factor complex is also pH-dependent, but the terminal ileal pH does not differ from normal in subjects with chronic exocrine pancreatic in-
malabsorption in such subjects results from the of an unphysiological test.
sufficiency.’7
24.
It has been observed, in humans and rats with exocrine pancreatic insufficiency, that vitamin-B12 malabsorption may be reversed by as little as 2 g. of pancreatic extract-a quantity with insignificant buffering action-and, on this basis, the presence of a pancreatic intrinsic factor has been proposed. Toskes et al. 24have isolated from hog pancreatic extract a factor that increases vitamin-B12 absorption to normal levels in humans and rats with exocrine pancreatic insufficiency. This factor is a thermolabile compound of molecular weight between 10,000 and 30,000 with proteolytic activity which is stable at pH 1-5 for 30 minutes. In the case of Zollinger-Ellison syndrome described by Shimoda et al. 15 the intraduodenal pH when fasting was 1, and this may have been sufficiently low to inactivate pancreatic intrinsic factor. This would not occur in subjects with chronic exocrine pancreatic insufficiency. It is tempting to speculate that excretion of this factor is stimulated by food and that, in subjects with chronic exocrine pancreatic insufficiency, quantities of the factor sufficient to ensure normal vitamin-B12 absorption may not be available in the fasting state. The mechanism for vitamin-B12 malabsorption in fasting subjects with chronic exocrine pancreatitis is still uncertain. However, the finding of vitamin-B1B
We thank the Wellcome Trust for
a
use
grant for technical
assistance; Prof. R. H. Girdwood, in whose department the study was carried out; and the staff of the Department of Clinical Chemistry for help with the pancreatic function tests. Requests for reprints should be addressed to D. J. C. S., Gastro-Intestinal Section, Department of Therapeutics, Royal Infirmary, Edinburgh EH3 9YW. REFERENCES 1. 2. 3. 4. 5.
6. 7. 8. 9. 10.
11. 12.
13. 14. 15. 16. 17.
18. 19. 20. 21. 22. 23.
McIntyre, P. A., Sachs, M. V., Krevans, J. R., Conley, C. L. Archs intern. Med. 1956, 98, 541. Perman, G., Gullberg, R., Reizenstein, P. G., Snellman, B., Allgén, L-G. Acta med. scand. 1960, 168, 117. Veeger, W., Abels, J., Hellemans, N., Nieweg, H. O. New Engl. J. Med. 1962, 267, 1342. Evans, W. B., Wollaeger, E. E. Am. J. dig. Dis. 1966, 11, 594. Warren, W. D., Leite, C. A., Baumeister, F., Poucher, R. L., Kaiser, M. H. Am.J. Surg. 1967, 113, 77. LeBauer, E., Smith, K., Greenberger, N. J. Archs intern. Med. 1968, 122, 423. Toskes, P. P., Hansell, J., Cerda, J., Deren, J. J. New Engl, J. Med. 1971, 284, 627. Nimmo, J., Finlayson, N. D. C., Smith, A. F., Shearman, D. J. C. Gut, 1970, 11, 163. Simpson, J. D., Shearman, D. J. C. Phys. Med. Biol. 1968, 13, 61. Finlayson, N. D. C., Simpson, J. D., Tothill, P., Samson, R. R., Girdwood, R. H., Shearman, D. J. C. Scand. J. Gastroent. 1969, 4, 397. Finlayson, N. D. C., Shearman, D. J. C., Simpson, J. D., Girdwood, R. H. J. clin. Path. 1968, 21, 595. Shearman, D. J. C., Boddy, K., Henderson, J. T., King, P. C., Simpson, J. D., Finlayson, N. D. C. Glaxo Symposium on the Cobalamins; p. 169. Edinburgh, 1971. Finlayson, N. D. C., Simpson, J. D., Shearman, D. J. C. Scand. J. Gastroent. 1970, 5, 261. Finlayson, N. D. C. Personal communication. Shimoda, S. S., Saunders, D. R., Rubin, C. E. Gastroenterology, 1968, 55, 705. Shum, H. Y., O’Neill, B. J., Streeter, A. M. Lancet, 1971, i, 1303. Benn, A., Cooke, W. T. Scand. J. Gastroent. 1971, 6, 313. Kaiser, M. H., Leite, C. A., Warren, W. D. New Engl. J. Med. 1968, 279, 570. Rhodes, J., Apsimon, H. T., Lawrie, J. H. Gut, 1966, 7, 502. Lawson, H. H., Rovelstad, R. A. ibid. 1969, 10, 215. McGuigan, J. E. J. Lab. clin. Med. 1967, 70, 666. Goldberg, L. S., Fudenberg, H. H. ibid. 1969, 73, 469. Shum, H. Y., O’Neill, B. J., Streeter, A. M. J. clin. Path. 1971, 24, 239. Toskes, P. P., Ginsberg, A. L., Conrad, M. E., Deren, J. J. Gastroenterology, 1971, 60, 806.
APPARENTLY ISOLATED EXCESS DEOXYCORTICOSTERONE IN HYPERTENSION A Variant of the Mineralocorticoidexcess
Syndrome
J. J. BROWN
J. B. FERRISS
R. FRASER D. R. LOVE
A. F. LEVER I. S. ROBERTSON
J. A. WILSON
Medical Research Council Blood Pressure Unit, Western Infirmary, Glasgow G11 6NT
Plasma-deoxycorticosterone (DOC) concentration was measured in thirty-one hypertensive patients, all with normal plasma-aldoSummary
Plasma-Doc concentration was six of the twenty-one patients in persistently high with low plasma-renin concentration and in none of the ten cases in whom renin values were normal. There were intermittently raised DOC levels in three further patients with low plasma-renin and in two cases in the normal-renin group. Intermittent hyposterone
values.
Adiposity is not necessarily directly related to overweight, but Billewicz et aU argue that, of the indices of adiposity commonly used, the weight/ standard weight ratio is the best index. We have expressed the weights of our patients similarly, as a percentage of the predicted mean weight for the corresponding age, height, and sex. Whilst our results show no evidence of overweight in the older age-groups, there is a tendency to overweight in the younger patients which is most noticeable in the 25-34 age-group. In the Framingham study, of the patients in whom gallstones developed during the period of the survey, the 40-49 age-group was significantly heavier than the control population. Of the symptoms experienced by patients with gallstones, pain is the most dramatic, being severe, French and Robb,8 protracted, and persistent. analysed fifty consecutive cases of gallstone colic and concluded that intermittent pain, as implied by the word colic, is rare. Although the epigastrium and the right hypochondrium were the commonest sites of pain, pain in the supracostal areas was common. No doubt some of the unusual pain sites are due to the patient’s inability to localise the pain; this is more probable if the nervous pathways involved are autonomic, as in distension of the biliary tract. Conversely, one would expect local peritonitis in association with cholecystitis to be accurately localised by the patient. On history alone, however, like French and Robb,8 we found that the site and nature of the pain did not indicate its precise cause. The apparent relief of pain by alkalis in almost a third of our patients is not understood but is a characteristic not exclusive to the pain of peptic ulcers. Symptoms of dyspepsia are not so easily evaluated. Price,9who interviewed a random sample of the female population in a general practice, found no difference in dyspeptic symptoms amongst females with normal or abnormal cholecystograms. In our patients, however, the symptoms of dyspepsia were usually relieved after cholecystectomy, and this agrees with the findings of Rhind and Watson.10 The two Whilst views are not necessarily contradictory. accepting that dyspepsia is common amongst women and that some may have coincidental gallstones which do not cause symptoms, this does not mean that patients who have dyspepsia as a result of biliary obstruction and inflammation will not have it relieved by cholecystectomy along with their pain. Heartburn was one of the more common dyspeptic symptoms and was usually relieved by operation. Southam 11 also found that patients with a positive cesophageal-perfusion test (i.e., patients who had symptoms of reflux with oesophageal perfusion by 0.1N hydrochloric acid) had a negative perfusionafter cholecystectomy. Tenderness in the right hypochondrium and epigastrium in patients with gallstones, with local signs of peritonitis, is expected if there is cholecystitis. Even between attacks of pain there may be an illdefined mass in the right hypochondrium indicating a distended gallbladder, a mucocele, or adherent omentum. Tests for hyperxsthesia are of doubtful in and our experience Boas’ sign is of no use. value, test
Only about a third of patients with a history of jaundice were subsequently found to have stones in the common bileduct, and over a third of the patients with common-duct stones gave no history of jaundice and had normal liver-function tests. We thank Mr. W. F. Nicholson for permission patients under his care. Requests for reprints should be addressed to N. K.
to
study
REFERENCES B. G. A. Gallstones and their
1.
Moynihan,
4.
1966, 19, 273. Glenn, F., McSherry, C. K. Surgery Gynec. Obstet. 1968, 127,
Surgical Treatment; p. 116. London, 1905. 2. Montegriffo, V. E. Ann. hum. Genet. 1968, 31, 389. 3. Friedman, G. D., Kannel, W. B., Dawber, T. R. J. chron. Dis. 1067. 5. Horn, G. Br. med. J. 1956, ii, 732. 6. Nix, J. T. Am. J. Gastroent., N.Y. 1965, 43, 208. 7. Billewicz, W. Z., Kemsley, W. F. F., Thomson, A. M. prev. soc. Med. 1962, 16, 183. 8. French, E. B., Robb, W. A. T. Br. med. J. 1963, ii, 135. 9. Price, W. H. ibid. p. 138. 10. Rhind, J. A., Watson, L. ibid. 1968, i, 32. 11. Southam, J. A. Br. J. Surg. 1969, 56, 671.
Br. J.
DOES MALABSORPTION OF VITAMIN B12 OCCUR IN CHRONIC PANCREATITIS ?
J. T. HENDERSON* J. D. SIMPSON R. R. G. WARWICK D. J. C. SHEARMAN Gastro-Intestinal Section of University Department Therapeutics,
of Department of Medical Physics, Royal Infirmary, Edinburgh EH3 9YW and
Seven patients with chronic pancreaSummary titis underwent vitamin-B12 absorption tests by the whole-body counting method. Four of the seven patients malabsorbed vitamin B12 in the fasting state, but absorption was normal when food was given. This may explain reports of vitamin-B12 malabsorption in chronic pancreatitis despite the rarity of vitamin-B12 deficiency. One patient with malabsorption in the fasting state had normal absorption when sodium bicarbonate or normal pancreatic juice was given. Introduction
MALABSORPTION of vitamin Bis was demonstrated by Mclntyre et al.l in four out of five subjects with chronic exocrine pancreatic insufficiency. This was not corrected by administration of exogenous intrinsic factor. Similar findings have since been reported by others. 2-7 However, the mechanism of vitamin-B12 malabsorption in subjects with chronic exocrine pancreatic insufficiency is still in dispute. Despite these reports of vitamin-BlI! malabsorption, deficiency of vitamin BlI! is very rare. Evans and Wollaeger4 mention two subjects with chronic exocrine pancreatic insufficiency, vitamin-Biz malabsorption, and mild macrocytic anaemia which responded to parenteral vitamin B12. LeBauer et al.report a single case of chronic exocrine pancreatic insufficiency, severe megaloblastic anaemia, and vitamin-B12 mal*
Present address: Department of Medicine, University of Edinburgh, Royal Infirmary, Edinburgh EH3 9YW.
242 TABLE I-CLINICAL DETAILS OF PATIENTS WITH CHRONIC PANCREATITIS
tained less than 0-02 (1.g. vitamin BI.2- Pancreatic supplements were not allowed for 24 hours before any test. Retention of cobalt-58 at 7 days of 30% or more is regarded as normal. Patient no. 1 was basally achlorhydric, but produced 10 meq. of acid in the first hour after pentagastrin in an intramuscular dose of 6 (1.g. per kg. The following separate studies were performed on this subject:
(1) Gastric acid secretion was stimulated by pentagastrin kg. intramuscularly 30 minutes before and 30 minutes after drinking 5"Co-labelled cyanocobalamin. (2) 135 ml. of pancreatic juice from a subject with normal pancreatic function was administered through a fine tube, the tip of which lay in the second part of the duodenum. The juice was given, at a rate of 1-5 ml. per minute, for 30 minutes before and for 1 hour after drinking s8Go-labelled cyanocobalamin. (3) Twenty milliequivalents of sodium bicarbonate in 200 ml. of water were administered by mouth over a period of 2 hours starting just before the 68Co-labelled cyanocobalamin 6 vg. per
*
t
Normal values: (a) volume >2’0 bonate conc. > 75 meq. per > 200 units per ml. Steatorrhoea > 7 g. fat per day.
ml. per kg.; (b) maximum bicarlitre; (c) maximum trypsin activity
absorption, but the ansemia may have resulted from folic-acid deficiency. All previous studies have assessed vitamin-Biz absorption using the Schilling test, where absorption is measured in the fasting state. We report here a comparison of vitamin-B12 absorption fasting and with food in subjects with chronic exocrine pancreatic insufficiency. Patients and Methods
Patients The clinical details of seven patients with chronic are shown in table I. No other cause for steatorrhcea could be identified in any patient. Pancreatic function tests were carried out using a Dreiling doublelumen tube.8 The pancreas was stimulated in patients 2 and 5 by intravenous secretin (Boots) in a dose of 3 units per kg. body-weight. In patients 1, 4, and 6 secretin (Karolinska) 1 unit per kg. was used. In patients 3 and 7 pancreatic function tests were not performed. In patient 3 a reliable pancreatic function test could not be performed because of a Polya partial gastrectomy. He presented with severe Steatorrhoea which improved with pancreatic supplements. In patient 7 the diagnosis was based on a history of recurrent upper abdominal pain, severe pancreatic calcification, and the response of Steatorrhoea to pancreatic
pancreatitis
supplements. Vitamin-B12 absorption was measured using a wholebody counter of shadow shield design.D,lO Each subject drank 0-5 .g. of cyanocobalamin labelled with 1 c. of cobalt-58 with 100 ml. of
water
after
a
days later. As
12-hour fast.
after this test was performed, but on this occasion the 58Co-labelled cyanocobalamin in 100 ml. of water was drunk in sips while the subject ate a vitamin-B12free meal. By Euglena gracilis assay, the meal itself conTABLE
drunk.
Results
Table 11 shows that malabsorption of vitamin B12 was found in four of the seven patients when assessed in the fasting state. In all four of these patients absorption of vitamin B12 was normal when a vitamin-B12free meal was eaten together with the oral dose of 68Co-labelled cyanocobalamin. In the remaining three patients absorption was normal in both tests. In table ill the results of the more detailed studies in patient 1 can be seen. Malabsorption of vitamin B12 TABLE III-EFFECT OF VARYING TEST CONDITIONS ON ABSORPTION IN PATIENT NO. 1
VITAMIN-Big
present in the fasting state with or without pentagastrin. Normal absorption occurred with food and when either pancreatic juice or sodium bicarbonate was administered in the fasting state.
was
Methods
Absorption was measured test as possible, a further
was
7
soon
II-VITAMIN-Bn ABSORPTION IN PATIENTS WITH CHRONIC EXOCRINE PANCREATIC INSUFFICIENCY: COMPARISON OF ABSORPTION FASTING AND WITH VITAMIN-B12-FREE MEAL
Discussion
Whole-body counting provides
a
quantitative
method of assessing vitamin-B12 absorption which does not depend on the collection of urine or faeces.9-12I The presence of retained but unabsorbed radioactivity can be excluded by profile scanning.13 There is a poor correlation between successive tests of vitamin-B12 absorption in the fasting state, but this improves when the tests are performed with food," probably because the latter test is more physiological. In this study we have confirmed that, in subjects with chronic exocrine pancreatic insufficiency, vitaminB12 absorption, measured in the fasting subject, may be depressed. However, we have demonstrated that vitamin-B12 absorption is normal when a vitamin-Bnfree meal is taken with the 5"Co-labellcd cyanocobalamin. Although it has previously been noted that absorption of 58Co-labelled cyanocobalamin is greater
243
when it is taken with a meal than when fasting,14 the increase in absorption in such circumstances is small compared with the large increase found in patients 1-4 in this study. The finding of normal absorption in non-fasting tests appears to offer a more plausible explanation for the absence of vitamin-B12 deficiency in subjects with chronic exocrine pancreatic insufficiency than the finding by Toskes et al. of a considerable variation in the ability to absorb vitamin B12 over a period of several months. In the one subject where several absorption studies were performed, the results suggest the possibility that a low intraluminal small-intestinal pH affects vitamin-B12 absorption. During fasting with or without pentagastrin stimulation, malabsorption of vitamin B12 was found. However, absorption was normal in fasting tests when either sodium bicarbonate or pancreatic juice was administered, and when food was given with the test. Such a conclusion is supported by the finding of vitamin-Bn malabsorption in the Zollinger-Ellison syndrome first reported by Shimoda et al.15 and subsequently by Shum et al. 16 The former workers reported reversal of vitamin-Bus malabsorption when the intraduodenal pH was maintained at 7. The intraduodenal pH in fasting subjects with chronic exocrine pancreatic insufficiency is lower than normal. 3, 17 However, after food the pH of the upper small intestine,18 as distinct from the duodenal bulb, 19,20 is similar in normal subjects and subjects with chronic exocrine pancreatic insufficiency. Thus the low pH in the duodenum 3,17 might be the cause of vitamin-B12 malabsorption in the fasting state, but the mechanism is not clear because this low pH will not affect significantly vitamin-B12intrinsic-factor binding. 21-23 Uptake of vitamin-B12intrinsic-factor complex is also pH-dependent, but the terminal ileal pH does not differ from normal in subjects with chronic exocrine pancreatic in-
malabsorption in such subjects results from the of an unphysiological test.
sufficiency.’7
24.
It has been observed, in humans and rats with exocrine pancreatic insufficiency, that vitamin-B12 malabsorption may be reversed by as little as 2 g. of pancreatic extract-a quantity with insignificant buffering action-and, on this basis, the presence of a pancreatic intrinsic factor has been proposed. Toskes et al. 24have isolated from hog pancreatic extract a factor that increases vitamin-B12 absorption to normal levels in humans and rats with exocrine pancreatic insufficiency. This factor is a thermolabile compound of molecular weight between 10,000 and 30,000 with proteolytic activity which is stable at pH 1-5 for 30 minutes. In the case of Zollinger-Ellison syndrome described by Shimoda et al. 15 the intraduodenal pH when fasting was 1, and this may have been sufficiently low to inactivate pancreatic intrinsic factor. This would not occur in subjects with chronic exocrine pancreatic insufficiency. It is tempting to speculate that excretion of this factor is stimulated by food and that, in subjects with chronic exocrine pancreatic insufficiency, quantities of the factor sufficient to ensure normal vitamin-B12 absorption may not be available in the fasting state. The mechanism for vitamin-B12 malabsorption in fasting subjects with chronic exocrine pancreatitis is still uncertain. However, the finding of vitamin-B1B
We thank the Wellcome Trust for
a
use
grant for technical
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APPARENTLY ISOLATED EXCESS DEOXYCORTICOSTERONE IN HYPERTENSION A Variant of the Mineralocorticoidexcess
Syndrome
J. J. BROWN
J. B. FERRISS
R. FRASER D. R. LOVE
A. F. LEVER I. S. ROBERTSON
J. A. WILSON
Medical Research Council Blood Pressure Unit, Western Infirmary, Glasgow G11 6NT
Plasma-deoxycorticosterone (DOC) concentration was measured in thirty-one hypertensive patients, all with normal plasma-aldoSummary
Plasma-Doc concentration was six of the twenty-one patients in persistently high with low plasma-renin concentration and in none of the ten cases in whom renin values were normal. There were intermittently raised DOC levels in three further patients with low plasma-renin and in two cases in the normal-renin group. Intermittent hyposterone
values.