HYPERBILIRUBINEMIA BY RICARDO KATZ, HECTOR DUCCI, AND HERNAN ALESSANDRI

Transcription

1 INFLUNC OF CORTISON AND PRDNISOLON ON HYPRBILIRUBINMIA BY RICARDO KATZ, HCTOR DUCCI, AND HRNAN ALSSANDRI (From the Deprtment of Mediine, University of Chile Medil Shool, Hospitl Slvdor, Sntigo, Chile) (Submitted for publiation November 26, 1956; epted My 1.6, 1957) Our exp~eriene (1), s well s tht of others (2I), in the tretment of ute heptitis with steroids, hs shown s the most striking effet rpid drop of serum bilirubin. This is ompnied by the lering of linil jundie. Solem nd Olsen (5) hve studied the influene of ACTH on the iteri index in ses of heptitis nd of posthepti jundie. In the former, it dropped very rpidly but in the ltter it ws not signifintly influened. They believed tht the different response of both types of jundie ould be used in the differentil dignosis. Sborov, Giges. Plough, nd Mndel (6) report se of posthepti jundie in whih ACTH did not indue lowering of hyperbilirubinemi. Johnson nd Doenges (7), in two ses of heptitis with hepnliulr jundie, observed rpid drop of serum bilirubin following the dministrtion of ACTH. In one of these ptients who hd ommon dut dringe the drop ws onomitnt with the reestblishment of biliry flow. Although they do not report results in ses of posthepti jundie, they suggest tht the hormone ould be useful in differentil dignosis s it would not.inflttene hyperbilirubinemi in this type of iterus. Aording Ptterson, Dingmn, Shwhmn, nd Thorn (8), ortisone hs holereti tion whih ould explin the lowering of the serum bilirubin vlues. Other investigrs () ielude the.inrese in biliry flow mong the frs whih ould explin the drop of hyperbilirulbinemi in ses of heptitis. Our findings in the first se of posthepti jundie who reeived ortisone prompted us study the influene of steroids in ses of omplete biliry obstrution. This ptient showed lerut drop of serum bilirubin in two periods in whih he reeived ortisone, despite rinom PromPi diret bifirubin Totl WMAin 'pft of * I2 o 12.0 dp \ It n Ober ho t0 100 I m b November FIG. 1. INFLUNC OF CORTISON ON SRUM BILIRUBIN IN POSTHPATIC JAUNDIC WITH COMPLT OBSTRUCTION DU TO CARCINOMA OF TH HAD OF TH PANCRAS Cse 1. 8 yerold mle. Hospitl number 5/

2 INFLUNC OF CORTICOIDS ON BLRUBINR[IA 171. y = v z t._ X * *2 ' 12 ~0 0e 6 Ol X 2 I s& 5 7 *9# *f Dys I * I* * 26~ FIG. 2. INFLUNC OF CORTISON ON SRUM AND URIN BILIRUBINS Cse 2. R.., 68 yerold femle. Hospitl number 56/76. The vlues for urine bilirubin in this nd the following figures re those obtined by Jendrssik nd Grof's method (15). of the hed of the pnres with omplete obstrution of the ommon bile dut, s shown t opertion (Figure 1). These results suggested tht the holereti effet, if present, ws not n importnt fr in the redution of serum bilirubin vlues. Moreover they showed tht jundie, even when due biliry obstrution, ws influened by ortisone. Chlmers nd ssoites (9) hve reently reported their findings with fourdy ACTH test in the differentil dignosis of jundie. they ob served definite overlpping of effets, thereby filing onfirm the usefulness of the test. Among their ptients with biliry obstrution, two showed more thn onethird drop of serum bilirubin despite no detetble urinry urobilinogen throughout the observtion period. It is interesting ll ttention, in reltion wht will be reported lter, the observtions of these investigrs in hroni hyperbilirubinemi. They found tht the drop in bilitubin in the mjority of ptients ws presumbly not result of inresed. X g SWO 50 or 0 1 %ft e...0, "Oko" dmbl milk, 2 5 6? 'I 00 onw 0 Urine 22 e // i~~_' ; 1 lo. *8 ~~~~~~~~~~~~~~~~~~~~~I. * 9 90 it X 1 w * I? if 1 U Dys PIG.. Imistk ei C6RTnBON ON SRUM AND (TRIN ILIRUBINS Cs. L;S'., 57 yeeold nile. Hspitl number 56/9226.

3 1 72 RICARDO KATZ, HACTOR DUCCI, AND HRNAkN ALSSANDRI h. C h so h SO 60 so x, z He 0 f 2 Dys FIG.. INFUNC OF CORTISON ON SRUM AND URIN BILIRUBINS Cse..G., 6 yerold fenle. Hospitl number 56/868. holeresis, beuse it ws ompnied by derese rther thn n inrese in fel urobilinogen output. MTHODS OF STUDY For the purpose of investigting the effet of steroids on hyperbilirubinemi of ses in whih holeresis ould not hve role, we hose ses of posthepti 1 jundie with omplete biliry obstrution. These ptients were seleted beuse they hd sustined fel holi (bsene of fel urobilinogen) due omplete biliry obstrution. Three reeived ortisone nd one prednisolone by the orl route for periods of 9 10 dys. The dosge is indited in Figures 2 through 5. During the bsl observtion period, during the dministrtion of the steroid, nd following its withdrwl, the following lborry tests were rried out serilly: prompt diret nd tl serum bilirubin (10, 11), fel nd urinry urobilinogen (12, 1), urinry bilirubin with Mlloy nd velyn's (1) nd Jendrssik nd Gr6f's (15) methods, nd the qulittive investigtion of fel bilirubin (pplition of Wtson nd Hwkinson's method (16) fees extrt). RSULTS The results obtined re shown grphilly in Figures 2 through 5. During the whole period of study the fel urobilinogen in the four ptients ws onstntly below 1 mg. per 2 hours nd the qulittive investigtion of fel bilirubin ws lwys negtive. It n be esily observed tht ortisone s well s prednisolone, given in doses similr those 1 Obstrutive jundie of other lssifitions. used by the uthors in the tretment of ute benign heptitis, produed mximl drops of serum bilirubin of 28 per ent from the initil vlue. This drop, lthough evident, is less thn tht observed by the present investigrs in ute heptitis during the first four dys of dministrtion of ortisone (55.7 per ent). The drop of serum bilirubin in our ses of omplete biliry obstrution ws ompnied by persistene of holi nd, in ontrst wht would be expeted, by redution of the urinry exretion of bilirubin. This redution, lthough vrible, ws observed in ll four ses during the dministrtion of the drug. It ws shown by the two methods used whih gve lmost identil vlues (urine preserved with sodium rbonte nd olleted under petroleum ether ws used throughout). After the withdrwl of the steroid the serum bilirubin inresed, rehing pretretment levels in three ses within four dys. In the other ptient (Cse No. ) bilirubin did not reh the bsl vlues; this ptient hd n importnt gstrointestinl hemorrhge during this period. In ddition the hnges in serum bilirubin, ll ptients showed n inrese in urinry bilirubin following disontinution of the steroid. DISCUSSION The results here reported demonstrte the effet of ortisone nd prednisolone on the hyperbilirubi

4 INFLUNC OF CORTICOIDS ON BILIRUBINMIA 17 6 Serum 10 urine 9*0 110 Re t \s~ ~~~~~ /,A S 0. inso/ 2 o0 r6\/o OD 01 ' 0 t0 0A _}o *0~~~~~~~~~~~~~~~~~ R ~~51 if 1I 9 If Of 57 if Dys FIG. 5. INFLUNC OF PRDNISOLON ON SRUM AND URIN BILIRUBINS Cse 5. R.M., 7 yerold femle. Hospitl number 56/121. C. nemi of posthepti jundie with omplete obstrution. The lowering of the serum bilirubin vlues, lthough less mrked thn tht observed in ute heptitis during similr periods, is lerly pprent. Conomitntly with the lowering of serum bilirubin, regulr derese of urine bilirubin ws observed. These findings permit the exlusion of n inrese in biliry flow or in urinry exretion of bilirubin s the uses for the lowering of hyperbilirubinemi. This ould then be explined by diminution of bilirubinogenesis. The formtion of bilirubin ould diminish by slowing down of red ell destrution or of hemoglobin brekdown. The metbolism of hemoglobin ould lso devite olorless ompounds whih do not ret with the dizo regent. The possibility nnot entirely be ruled out tht the effet of the steroids is exerted on the liver, nd tht hepti bilirubinogenesis whih is inhibited by them ould exist. The results reported suggest the possibility tht the effet of ortisone on bilirubinogenesis my ply role in the rpid drop of serum bilirubin in ute heptitis. RFRNCS 1. Dui, H., nd Motlis, J., Heptitis fulminntereuperion. Rev. MWdi de Chile, 1951, 79, vns, A. S., Sprinz, H., nd Nelson, R. S., Adrenl hormone therpy in virl heptitis. I. The effet of ACTH in the ute disese. Ann. Int. Med., 195, 8, Siegenthler, W., nd Suter, L., Zur Behndlung der Heptitis epidemi mit Cortison. Shweiz. med. Whnshr., 1955, 85, Huber, T.., nd Wiley, A. T., Cortisone in the tretment of infetious heptitis. Ann. Int. Med., 1955, 2, Solem, J. H., nd Olsen, A., The ourse of iterus index nd prothrombin vlue during ortiotropin tretment of ute heptitis nd obstrutive jundie. A preliminry report. At med. Sndinv., 195, 16, Sborov, V. M., Giges, B., Plough, I. C., nd Mndel, W., ACTH therpy in ute virl heptitis. J. Lb. & Clin. Med., 195,, Johnson, H. C., nd Doenges, J. P., Intrhepti obstrutive jundie (primry holestsis), liniopthologi syndrome of vried etiology: review with observtions of the use of ortiotropin s dignosti ol. Ann. Int. Med., 1956,, Ptterson, P. R., Dingmn, J. F., Shwhimn, H., nd Thorn, G. W., Cholereti tion of ortisone. New nglnd J. Med., 195, 251, Chlmers, T. C., Gill, R. J., Jernign, T. P., Sve, F. A., Jordn, R. S., Wldstein, S. S., nd Knowln, M., vlution of fourdy ACTH test in the differentil dignosis of jundie. Gstroenterology, 1956, 0, Dui, H., nd Wtson, C. J., The quntittive determintion of the serum bilirubin with speil referene the promptreting nd the hloroformsoluble types. J. Lb. & Clin. Med., 195, 0, Mlloy, H. T., nd velyn, K. A., The determintion of bilirubin with the phoeletri olorimeter. J. Biol. Chem., 197, 119, 81.

5 17 RICARDO KATZ1ftiF;CTOR IUMIu, ARD HRNAM ALZSSANDRI 12. Wtson, C. J., Studies on urobilinogen. I. An improved method for the quntittive estimtion of urobilinogen in urifte nd fees. Asu. J. Cfln. Pth., 196, 6, Shwrtz, S., SboroV, V., nd Wtson, C. J., Studies of urobilinogen. IV. The Quntittive determintion of urobilinogen by mens of the velyn phoeletri olorivneter. Am. J. Clii. Pth., 19*,; Mlloy, H. T., nd *lyn, K. A., Oxidtion method for bilirubin determintion in bile nd meonium with the phoeletri olorimeter. J. Biol. Chem., 198, 122, Jendrssik, L., nd Gr6f, P.; Verfhren zur phometrishen Bestimmung des Bilirubins im Hm. Biohkm. Ztfthr., 198, 296, Wteon, C. J., nd HiWkiiison, V., Semiquntittive estimtion of bilirubin in the urine by mens of the brium,frip..ndifitioni of Hirrison's tests. J. L5. & Clin. 1ed., fm6, 1, 91.