Serum studies in man after administration of

Transcription

1 Gut, 62, 3, 74 IL Serum studes n man after admnstraton of vtamn A acetate and vtamn A alcohol In subjects sufferng from dsturbances of absorpton and dgeston OLIVER ITZGERALD, JAES J. ENNELLY, AND DANIEL J. HINGERTY rom St. Vncent's Hosptal and Unversty College, Dubln SYNOPSIS Vtamn A acetate and vtamn A alcohol, trolen 13', olec acd 1131, and fat balance tests have been assessed n studes on cases of coelac dsease, pancreatc nsuffcency, and some dsorders of the small ntestnal wall. In coelac dsease a very low serum carotene and flat vtamn A absorpton curves have been noted. The contrast between vtamn A acetate and alcohol curves has been clearly shown n cases of pancreatc dsorder showng maldgeston. The correlaton between vtamn A and trolen 1131 absorpton (.9) s closer than that between vtamn A and fat balance. In assessng ntestnal absorpton serum carotene fgures are of value only f very low fgures are found. Some of the many factors whch may affect vtamn A absorpton n the normal subject have already been noted (tzgerald, ennelly, and Hngerty, 61). One mght note n partcular the effect of det and exercse. In ths paper the results of tests carred out on patents wth coelac dsease, pancreatc dsease, and other condtons nvolvng the almentary tract wll be dscussed. Where possble, the vtamn A tests wll be compared wth other absorpton tests, such as fat balance, trolen 1131 absorpton, olec acd 1131 absorpton and wth serum carotene. The dfferental absorpton of vtamn A acetate and vtamn A alcohol n pancreatc defcency wll also be dscussed. Low fastng plasma vtamn levels and flat absorpton curves after ngeston of vtamn A are accepted fndngs n coelac dsease (Chesney and ccoord, 34). Usually there s lttle dfference n these cases between absorpton of the vtamn from oly and aqueous phases, though ox (49) dd fnd good absorpton curves n coelac patents after ngeston of emulsfed vtamn A. Excellent absorpton of vtamn A n an aqueous phase compared wth the flat curves followng tests wth an oly preparaton has been observed n cystc fbross of the pancreas (Lews, Bodansky, Brmngham, and Cohlan, 47). oreover, pancreatn, admnstered durng the test n these cases, has been shown to rectfy a prevously abnormal curve. ollowng gastrectomy some patents show subnormal absorpton whereas others reveal earler peaks n absorpton than do normal subjects (endeloff, 54). Other condtons studed n whch poor absorpton was found were tuberculoss (Breese, Watkns, and ccoord, 42), ble duct atresa (ay, Blackfan, ccreary, and Allen, 4), and jejuno-lets (Adlersberg and Sobotka, 43). ATERIAL AND ETHODS The vtamn A absorpton tests were carred out as descrbed earler (tzgerald et al., 61). Trolen 1131 and olec acd 1P31 absorpton tests were carred out as descrbed by ennelly, tzgerald, and Healy (59). or the evocatve serum enzyme test the method of Howat, Duncan, Harper, Oleesky, Scott, Smth, and Varley (55) and later descrbed by Burton, Hammond, Harper, Howat, Scott, and Varley (6) wth mnor modfcatons as regards tme was used. RESULTS Normal absorpton fgures have already been noted, namely, a fastng level of to 3.u. % rsng to over.u.% after 25,.u.% of vtamn A 74 Gut: frst publshed as.1136/gut on 1 arch 62. Downloaded from on 17 July 21 by guest. Protected by copyrght.

2 Serum studes n man after admnstraton of vtamn A acetate and vtamn A alcohol taken orally, the fgure beng smlar for vtamn A acetate and vtamn A alcohol preparatons. Peak fgures between 6 and.u. % are suggestve of malabsorpton but need further evdence for defnte dagnoss. Peak fgures falng to rse over 6.u. % defntely ndcate malabsorpton. The normal fastng serum carotene level was taken as over,tg. % (tzgerald et al., 61). Normal subjects showed peak absorpton after ngestng trolen 1131 of over 12% of the test dose. aecal excreton should not exceed 4% of the ngested dose n a 72 hours' collecton. at balance results were expressed n g./day faecal excreton on a det of 5 to g./day. Less than 6 g. was excreted normally. IN COELIAC DISEASE AND OTHER INTESTINAL DIS- ORDERS The man conclusons whch can be derved from Table I are that patents wth coelac dsease showed poor absorpton of both vtamn A acetate and vtamn A alcohol and also a low fastng serum carotene level. 1 Coelac dsease (on treatment) Dagnoss Coelac dsease Coelac dsease (on treatment) Coelac dsease (on treatment) Coelac dsease (on treatment) Coelac dsease (on treatment) Dagnoss Case 1, an adult, had had steatorrhoea for many years; hypocalcaema, fatty darrhoea, abdomnal dstenton, weght loss, and osteomalaca were also present. She responded well to a gluten-free det and, as can be seen, vtamn A absorpton and trolen 1131 absorpton mproved slghtly durng the frst sx weeks of treatment. The falure of serum tolerance tests to respond better s possbly due to the rapd tssue uptake of vtamn A and trolen 131 n a patent wth a long hstory of malabsorpton. Table II shows results n tests carred out on patents wth other condtons nvolvng the small ntestne. Though classcal ulceratve colts does not nvolve the small ntestne poor ntestnal absorpton may occur n ths condton (Sandwess and Levy, 57). It can be seen that peak fgures, whle hgher than those n coelac dsease, are stll abnormal. There s a strkng dfference between the fastng serum carotene levels n Tables I and II. In only one member of ths group (Table II) was the serum carotene level unusually low. BLE I COPARATIVE STUDIES O VITAIN A AND OTHER TESTS IN COELIAC DISEASE (JUVENILE AND ADULT) Treatment Age Sex Vtamn A Vtamn A Serum Trolen (yr.) Acetate Alcohol Carotene 11 (.u. %) (. U.%) (g.%) Dose n (Peak) (Peak) Serum at Peak (%) Gluten-free det (59) (59) Gluten-free det (57) Gluten-free det Gluten-free det Gluten-free det Gluten-free det Progressve systemc scleross Lymphosarcoma (ntestnal) After massve resecton of small ntestne Post-gastrectomy darrhoea Post-gastrectomy darrhoea Ulceratve colts Intestnal monlass Intestnal monlass TABLE II COPARATIVE STUDIES O VITAIN A AND OTHER TESTS IN INTESTINAL DISORDERS OTHER THAN COELIAC DISEASE Age Sex Vtamn A Vtamn A Serum Trolen 1131 (yr.) Acetate Alcohol Carotene Dose n (.u. %) (.u. /) GAg. %) Serum at (Peak) (Peak) Peak (%) ' faecal excreton 75 at Excreton (g.iday) 5 at Excreton (g./day) Gut: frst publshed as.1136/gut on 1 arch 62. Downloaded from on 17 July 21 by guest. Protected by copyrght.

3 Olver tzgerald, James J. ennelly, and Danel J. Hngerty IN PANCREATIC DISEASE These tests were carred out on 27 patents wth pancreatc dsease of varous types, namely, chronc relapsng, calcareous, postgastrectomy, or heredtary pancreatts and ampullary carcnoma. Tables III and IV show results n patents found to have normal and subnormal absorpton respectvely. g. 1 shows the contrast between the absorpton of vtamn A acetate and vtamn A alcohol n pancreatc malabsorpton. It s worth notng that the mean absorpton fgures n normal subjects for vtamn A acetate are slghtly hgher than those of vtamn A alcohol. or purposes of descrpton results are dvded nto two groups, dependng upon whether there s or s not any objectve sgn of a dsturbance of dgeston leadng to an absorpton defect (Tables III and IV). In Table IV are shown results of tests n patents wth pancreatc dsease who showed malabsorpton on fat balance studes or on the bass of poor serum Case Age (yr.) Dagnoss 1,25 3,5 1,55 1,5 1,973 1, 4, 2,62 1, ,659 2,522 1,2 Stenoss of sphncter of Odd Carcnoma of ampulla Chronc relapsng pancreatts Chronc relapsng pancreatts Chronc relapsng pancreatts Chronc relapsng pancreatts Post-gastrectomy pancreatts 22 Calcareous pancreatts 23 Stenoss of sphncter of Odd 24 Chronc relapsng pancreatts 25 Calcareous pancreatts 1,4 9 1,5 1, 1,952 1,96 4,3 3 1, ,76 2,56 1, TABLE III lpd response, depressed trolen 1131 absorpton, and often by steatorrhoea and loss of weght. The absorpton pattern was followed repeatedly over some years n fve patents. Case 15 (Table IV) had stenoss of the sphncter of Odd wth evdence of malabsorpton. After a sphncterotomy ths absorpton returned to normal. Case 21 developed pancreatts followng a partal gastrectomy and as the pancreatc dsease progressed absorpton deterorated. Case 24 showed smlar changes. Cases 22 and 23 (a father and daughter) had normal absorpton curves n 54 and 55 at a tme when both complaned of symptoms referable to pancreatts. Wth subsequent deteroraton n the condton of both patents ther curves became abnormal. At operaton sgns of pancreatc abnormalty were present n both. Case 23 ganed 3 lb. n weght followng a sphncterotomy and excson of a polvp n the pancreatc duct. STUDIES O VITAIN A AND OTHER TESTS IN CASES O PANCREATIC DISEASE WITH APPARENTLY NORAL INTESTINAL ABSORPTION Sex Vtamn A Acetate Vtamn A Alcohol Serum Carotene at Balance as g. aecal (.u.y%) (.u. Y.) (Jsg. %) at/day (5 g. fat det) S (56) 435 (59) 5 3, (54) 299 (5) 22 3,(55) 29 (59) 46 1,14 (56) 5 (5) , (56) 4 (59) 2,12 (54) 36 (5) 2,27 (55) 2,161 (59) 1,65 (56) 1,45 (5) Trolen " Dose n Serum at Peak (%/) TABLE IV COPARISON BETWEEN VITAIN A AND OTHER TESTS IN PATIENTS WITH PANCREATIC DISEASE SHOWING ALABSORPTION Age Sex Peak Serum Peak Serum astng Serum at (yr.) Vtamn A Vtamn A Carotene Balance Acetate Alcohol (mg. Y.) (g./day) (.u.%) (.u. /) % dred weght Serum Peak Trolen "11 (%o/) (59) 6- (59) Gut: frst publshed as.1136/gut on 1 arch 62. Downloaded from on 17 July 21 by guest. Protected by copyrght.

4 ,2 4 2 Serum studes n man after admnstraton of vtamn A acetate and vtamn A alcohol -1 PEAK VITAIN A ACETATE 1. IG. 1. Contrast between absorpton of vtamn A alcohol and vtamn A acetate n patents wth pancreatogenous steatorrhoea.... ean (malabsorpton) ean (normal) Range of peaks n pancreatc patents wth nalabsorpton IG. 3. 2' 4. 6 p4 W6 1- et' 2o VITAIN A ALCOHOL 1 2J _O / , t e6. 15 VITAIN A PEAK I.U. '/ Correlaton between vtamn A absorpton andfat balance n 14 patents. Coeffcent of correlaton -62 (P = < 2). 1 1q z J Q 2. IS I--. 5 S 2C % O VITAIN A DOSAGE IN BLOOD. IG. 2. Percentage of trolen Ip31 dosage n total blood volume (7.7% body weght) at peak showng correlaton between vtamn A and trolen absorpton n 15 patents. Coeffcent of correlaton =.9 (P <.1). The three absorpton tests most wdely used at present are fat balance studes, vtamn A absorpton, and radoactve tagged fat absorpton (trolen 1131 and olec acd 1131). We have attempted to correlate these tests n patents who had more than one of them. In gs. 2 and 3 are shown comparsons between vtamn A absorpton and trolen 1131 and vtamn A absorpton and fat balance tests. Shngleton, Bayln, Isley, Sanders, and Ruffn (57) referred to the contrast n trolen and olec acd absorpton n four cases of pancreatc defcency. In g. 2 both trolen 1131 and vtamn A results are expressed as the percentage of the ngested test dose found n the total blood volume, the blood volume beng taken as 7-7% body weght n klograms. There s a hgh degree of correlaton between the vtamn A and trolen 1131 absorpton tests. The coeffcent of correlaton s 9 (P < 1). Study of the fat balance and vtamn A results n g. 3 ndcates a lesser degree of correlaton between these tests. There s much greater scatter of ponts around the lnes representng the mean fgures, the coeffcent of correlaton beng only 61 n ths case (P < O'2). It has already been ponted out 77 Gut: frst publshed as.1136/gut on 1 arch 62. Downloaded from on 17 July 21 by guest. Protected by copyrght.

5 7 Olver tzgerald, James J. ennelly, and Danel J Hngerty that serum tolerance tests depend on factors other than absorpton alone, so t s to be expected that there would be closer correlaton between one serum tolerance test and another rather than between a serum tolerance test and a balance test. DISCUSSION Because of the varaton n results obtaned wth vtamn A absorpton tests n both normals and abnormals noted by some- authors (endeloff, 54; Hllman and Becker, 57) ths test has been less frequently used than other absorpton tests, such as fat balance or the more recently ntroduced 1131 tagged fats, both of whch have been much used (Shngleton et al., 57; Beres, Wenger, and Krsner, 57; Duffy and Turner, 5). Our experence wth the vtamn A tests has led us to conclude that t s a satsfactory test and may have certan advantages over other tests for the followng reasons:-it s less laborous than the commonly used fat balance test, both for patents and medcal personnel. Results can be made avalable on the day of the test. The dfference between normal peak fgures (.u. % and upwards) and abnormal fgures (generally peak fgures below 6.u.%) s usually clear cut. Seral tests may be used f requred, for example, n order to follow changng patterns of dsease wthout hazard to the patent, such as mght occur wth 1131 tagged fat; weekly repetton of vtamn A absorpton tests s qute feasble. The dfferental absorpton curves of vtamn A acetate and vtamn A alcohol preparatons may gve useful nformaton n studyng pancreatc dsease. Our use of ths test has been restrcted almost completely to adults, as repeated phlebotomy n chldren for 5 ml. of blood s dffcult and may be hazardous f the external jugular vens have to be used. If the test s used n chldren t s essental to gve doses calculated accordng to body weght (5, to 7,.u./kg. body weght). Patents wth actve coelac dsease usually show low serum carotene (mostly under 2,ug. %), subnormal fastng vtamn A levels and a poor serum response to oral admnstraton of both acetate and Case Dagnoss Post-gastrectomy pancreatts Stenoss of sphncter of Odd Calcareous pancreatts alcohol preparatons of vtamn A. All the subjects n Table I had these characterstcs. In two cases t was possble to demonstrate the clncal mprovement by the vtamn test after the use of a gluten-free det. As shown n Table II the fgures n other ntestnal dsorders, though abnormal, were hgher than those of patents wth coelac dsease. Serum carotene was subnormal n only one of eght cases. The acetate and alcohol preparatons were both poorly absorbed, vtamn A alcohol gvng a slghtly hgher peak fgure. Evdence of malabsorpton was present bochemcally n fve of eght cases. In the other three the tests were carred out because of weght loss. These cases would appear to refute the belef that fastng serum carotene estmaton alone s of value n studyng malabsorpton. The contrast n absorpton of vtamn A alcohol and vtamn A acetate was noted n patents wth cystc fbross of the pancreas (Breese and ccoord, 39). ore recently Lews et al. (47) have ponted out a smlar contrast usng aqueous and oly preparatons of the vtamn. In our studes on pancreatc dsease we have been mpressed wth the contrast n absorpton of the vtamn A alcohol and vtamn A acetate whch appeared n 32% of the cases studed. Table IV and g. 1 show ths fact qute clearly. Three patents (Cases 22, 23, and 24, Table IV), who had normal absorpton capacty when they frst presented wth symptoms of pancreatts, later developed characterstc defects due to the progress of the dsease. As vtamn A acetate also depends on pancreatc lpase for ts proper absorpton the dsparty between trolen and olec acd absorpton curves should be smlar to those of vtamn A acetate and vtamn A alcohol. In Table V we have shown the results of both tests carred out on three pattnts wth pancreatc defcency. It can be seen that the correlaton s strkng. There s defnte smlarty between the absorpton rato of vtamn A alcohol/vtamn A acetate and that between olec acd 1131 and trolen erst, eldman, Solomon, and Langsam (5) ponted out that correlaton between fat balance tests and vtamn A absorpton tests had not yet been proved, but they showed that absorpton of LE V COPARISON O SERU CURVES ATER DOUBLE VITAIN A AND DOUBLE AT TESTS IN PATIENTS WITH PANCREATITIS Serum Levels Vtamn A (.u."%) PercentagDe of Ingested Serum at Peak Level Dose of 1131 n Acetate Alcohol Trolen , Olec Acd 13 Gut: frst publshed as.1136/gut on 1 arch 62. Downloaded from on 17 July 21 by guest. Protected by copyrght.

6 Serum studes n man after adnnstraton of vtamn A acetate and vtamn A alcohol 79 trolen 1131 and vtamn A acetate were related n 2 5 % of cases. astng serum carotene fgures were normal n all cases of pancreatts, except n Cases 16 and 22, both of whch had reached that advanced stage of the condton when absorpton of both forms of vtamn A may be abnormal. The correlaton between these tests, as shown n gs. 2 and 3, ndcates that the trolen 1131 and vtamn A absorpton tests are equally useful. There appears to be less correlaton between fat balance and vtamn A absorpton tests. As these tests were carred out n 2 subjects varyng from normal to abnormal the fgures are of some value. One of us (J.J..) wshes to acknowledge wth thanks a grant from the edcal Research Councl of Ireland whch has also contrbuted towards the general expenses of the study. Professor E. J. Conway,.R.S., s to be thanked for hosptalty and use of apparatus. Dr. R. J. ansfeld helped greatly n the earler stages of ths study. We are grateful to many clncal colleagues for access to patents, and partcularly to Dr. W. O'Dwyer and Dr. G. Doyle of the Chartable Infrmary, Jervs St. We are ndebted to essrs. Roche Products for lberal supples of the vtamn A preparatons used and to essrs. Boots Pure Drug Company for supples of Secretn and Pancreozymn. REERENCES Adlersberg, D., and Sobotka, H. (43). at and vtamn A absorpton n sprue and jejuno-lets. Gastroenterology, 1, 357. Beres, P., Wenger, J., and Krsner, J. B. (57). The use of I131 trolen n the study of absorptve dsorders n man. Ibd., 32, 1. Breese, B. B., and ccoord, A. B. (39). Vtamn A absorpton n celac dsease. J. Pedat., 15, 15. Watkns, E., and ccoord, A. B. (42). The absorpton of vtamn A n tuberculoss. J. Amer. med. Ass., 1, 3. Burton, P., Hammond, E.., Harper, A. A., Howat, H. T., Scott, J. E., and Varley, H. (6). Serum amylase and serum lpase levels n man after admnstraton ofsecretn and pancreozymn. Gut, 1, 125. Chesney, J., and ccoord, A. B. (34). Vtamn A of serum followng admnstraton of halver ol n normal chldren and n chronc steatorrhea. Proc. Soc. exp. Bol. (N. Y.), 31, 7. Duffy, B. J., and Turner, D. A. (5). The dfferental dagnoss of ntestnal malabsorpton wth I1"'-fat and fatty acd. Ann. ntern. ed., 4, 1. ennelly, J. J., tzgerald,., and Healy, J. B. (59) labelled trolen (glyceryltroleate) and olec acd's3 absorpton studes as an ndex of small ntestnal functon. Irsh J. med. Sc., p erst, S.., eldman, S.., Solomon, N., and Langsam, A. (5). An evaluaton of the sotopc odotrolen method; ts correlaton wth vtamn A absorpton. Gastroenterology, 35, 31. tzgerald,., ennelly, J. J., and Hngerty, D. J. (61). Serum studes n man after admnstraton of vtamn A acetate and vtamn A alcohol. I. In normal subjects. Gut, 2, 263. ox, H. J. (49). Absorpton of unemulsfed and emulsfed vtamn A n sprue. J. Lab. cln. ed., 34, 114. Hllman, R. W., and Becker, N. H. (57). Absorpton of ngested vtamn A. Gastroenterology, 32, 73. Howat, H. T., Duncan, P. R., Harper, A. A., Oleesky, S., Scott, J. E., Smth, J., and Varley, H. (55). Clncal sgnfcance of changes n serum amylase and lpase n man after stmulatng the pancreas wth secretn and pancreozymn. Quart. J. ed., 24, 412. Lews, J.., Bodansky,., Brmngham, J., and Cohlan, S. Q. (47). Comparatve absorpton excreton and storage of oly and aqueous preparatons of vtamn A. J. Pedat., 31, 496. ay, C. D., Blackfan, K. D., ccreary, J.., and Allen,. H., Jr. (4). Clncal studes of vtamn A n nfants and n chldren. Amer. J. Ds. Chld., 59, endeloff, A. I. (54). The effects of eatng and of sham feedng upon the absorpton of vtamn A palmtate n man. J. cln. Invest., 33, 15. Sandwess, D. J., and Levy, S. H. (57). Gastrontestnal absorpton wth olec acd-11' and L-methonne-S3" n patents wth ulceratve colts. Proc. Soc. exp. Bol. (N. Y.), 95, 259. Shngleton, W. W., Bayln, G. J., Isley, J. K., Sanders, A. P., and Ruffn, J.. (57). The evaluaton of pancreatc functon by use of I"3' labelled fat. Gastroenterology, 32, 2. Gut: frst publshed as.1136/gut on 1 arch 62. Downloaded from on 17 July 21 by guest. Protected by copyrght.