Exocrine pancreatic function tests : A review

Exocrine pancreatic function tests (PFTs) remain of value in the diagnosis and assessment of chronic pancreatic disease. Direct intubation PFTs, using secretin/cholecystokinin or secretin/caerulein as the stimulants, continue to the the 'gold standard', although they are invasive, expensive and time consuming. Tubeless indirect tests, ie, the N-benzoyl-L-tyrosyl-para-aminobe-zoic acid and pancreolauryl tests, have gained increasing acceptance particularly as screening tests. The fecal measurement of chymotrypsin remains a useful screening test for pancreatic insufficiency and fecal fat testing standard for steatorrhea. Radioisotope tests are now outdated. Estimation of pancreatic markers in serum, urine and body fluids are useful when abnormal hut miss mild disease. Combining PFTs with imaging techniques provides a rational approach to early diagnosis and gives a better assessment of the patient with chronic pancreatic disease.

The test 1~ performed after an overnight fast and panc reatic enzyme supplements should he discontinued at least five days prior LO the !>Ludy.Drug~ or fond rc~ulung in a high urinary cxcreuon of aromatic ammo ,1L 1ds mw,t he avoided beforehand.The NBT-PABA givcn in a dose hetwccn 0. 5 and I g provide~ the greatest sensnivity (55-57).A test meal is recommended to s timulat e pancreatic secret ion (52,54 ,58-60); tea or mineral water is encouraged tu ensure sufficient diuresis and urine collection over 6 his generally sufficient (60,61 ).
Some modificauons uf th e test have hccn developed to overcome the high incidence of the false positives.A control test on an additional study day hy administering free PABA instead of NBT-PARA is commonly used (58).From the PARA excretion rnce ,ma test day (T) and a control day (C), the PABA excretion index (PEI) is derived (PEI= T/C).Nonpancrearic disease will influence hoth T a nd C, while pancreatic dysfunction only T, thus by using PEL false positives can he minimized.A PEI value of greater th an 82% b cons idered nurmal (20).A si ngle day NRT-PABA test has been developed as an alternative in order tn obrnin a PEI from one study day.The subjects are given free 14 C-PABA (67)(68)(69)(70) or paramninosalicylic acid (PAS) (71,72) in addit ion to the normal administration of NBT-PABA.The excretion rate of PABA and 14 C-PABA or PAS are determined respectively.PEI is the ratio of PABA : 14 PABA or PABA:PAS.But the assay techniques in these rests arc more complex and rewlts can be inval idatcd hy drug or isotopic in terference ( J 6).The measu rement of PABA in sc rum at between 90 and 150 mins after the administration of NBT-PABA is a convenient alternati ve to char of urine col lection, especial ly in children, elderly pauents or those with renal disorders.In most studies results have been sa tisfoctmy (73)(74)(75)(76)(77)(78)(79) while the simulrnneous scrum and unnary measurements of PABA may also improve the specificity hut nm the sensitivity of the NBT-PABA test (56,80). 156 The tluorcsccin Jdaurate test (FDT [pancreolauryl test, PLTJ) was first descrihed in 1969 (81 ), but has 1mly recently ncrractcd widespread interest.The principle of the test is similar t0 that of the NBT-PABA test.Fluorcsccin Jih1urate, a poorly water soluble synthetic ester, is given orally and cleaved hy pancreatic cstcrnses to l,1u ric acid and tree tl unresccin, which is water soluble nnJ excreted m urine.In comparison with the NRT-PABA test, FDT undergoes less interference fmm drugs or scrum components, t1nly requires simple hydrolysis and is more independent of renal function ( 16).The FDT test h as hccn standardized and is commercially ,l\'ailablc (Temmler; Mnrburg, West Germany).
The test is performed after fasting, and pancreatic supplements or vi tamin B preparati1ms, which interfere with fluorcscein measurements, have to he stopped.On the test Jay a capsule conmining 0. 5 mmol flunrescein dilaurntc b administered together with breakfast, while on the cont1\)I Jay 0.5 mmol free fluoresccin b given.Free fluids and a normal lunch are encouraged LO mainr;iin an adequate diuresis.Urine is collected tWer 10 h .Un nary flunresccin on the test (T) and control day (C) is measured photometrically n r flut1rometrically and th e fluorcsccin exc reti on index (FEI) obtained (FEl=T/C).An FEI over 30'10 rndicates normal; less th an 20% ahnormal; between 20 and 30% requires a repeated test.If the rereatcd test shows a ratio of less than 30%, it b considered abnormal.Recent st udies til FDT rndicme a sensitivity ranging from 46 co 100% with most studies between 75 and 93%, and specificity between 46 and 97% ( 13,16).Diseases assoc iated with false posi ti ve results arc similar to those for the NBT-PABA test.Most studies show the sensitivity ofFDT w he surenor to that nfNBT-PABA test (59,(82)(83)(84).
In order co shonen the test period and avoid the need to collect urine, fluorescein determinati,ms in scrum ha\'c been dcvelliped.Optimal flu,irescein scrum concentrations arc found hetwcen 4 and 6 h after oral ingestion.Scrum testing seems to offer scnsnivn y and specificity similar w those o( the urine test (79,(85)(86)(87).A modified FDT with fluorescein serum determination following merocloprnmide 10 enhance g::istric emptying ,rnd secrcun stimulation appears superior w the urine test (88).Feca l tests: Fecal micrnscopic cxaminatitm ,la random ,totil sample rs simple but unrel iable.Fecal fat and nitrogen tests have con tinu ed as routine tests for assessing steatorrhca, hut they c,mnnt d istrngu ish pancr<::atlt fro m nonpancrcatic disease.Stemm rhea and azotorrhea me late symptnniof pancreatic d isease, and llllly occur when the lipase 11u tput tall, hehm 10'\, of norm,il (99).The degree of pan.creatic impairment, as measured hy the intuharron 1es1s, may not reflect the scverit y of Mcatorrhe,1.Therefore, for sophisticated C\'aluatinn of the func tional reserve capacity n l the exocri1w pancreas both int uha1 ion tests and fecal tests have been considcrl•d neces,ary (90).Fecal fat estimation of 72 h srool collection remains the srnndarJ teM to quantify fat ma lahsorption (3, I 3,91 ).
Fecal c h ymc)trypstn measurcrnems can he dtme on random stool sample, (95-97), a lthough a 24 h collecnon ot feces may provide ~lightly better result, (98,99).From the present data the measurements still remarn a useful screening I CM lllr cxllcrine pancrear1C insufficiency.Recently, new photo• metric methods using standard lahoratory equipment have been developed, which make th1, test even more accessible than rhe traditional titrimetric method ( I 00-103 ).The sen. siti vr t y of the test ranges from 72 to 90",, and specif"icity from 62 to 90% {3-13).Stoo l samples col lected from l'lll• pat ients can he marled to the diagnostic c.:entre perform mg the assay w1rhou1 affecting test results.The test mc1y, therefore.he partirnlarly helpful in follow-up studies.

TABLE 1
Exocrine pancreatic function tests

TABLE 2
Data of the exocrine pancreatic function tests