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Assessment of Pancreatic Exocrine Function

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Assessment of Pancreatic Exocrine Function Immunological studies on type I diabetes in identical twins 99 RDG. The significance of the concordance rate for type 1 (insulin- Autoantibodies in newly-diagnosed diabetic children immunoprecipitate dependent) diabetes in identical twins. Diabetologia 1988; 31: 747-50. human pancreatic islet cell proteins. Nature 1982; 298: 167-9. 6 Gepts W. The pathology ofthe pancreas in human diabetes. In: Andreani D, Di 17 Baekkeskov S, Aanstoot HJ, Christgau S, et al. Identification of the 64K London: GABA-synthesizing enzyme Mario U, Federlin KF, Heding LG, eds. Immunology in diabetes. autoantigen in insulin-dependent diabetes as the Arch Dis Child: first published as 10.1136/adc.69.1.99 on 1 July 1993. Downloaded from Kimpton Medical, 1984: 21-34. glutamic acid decarboxylase. Nature 1990; 347: 151-6. 7 Lernmark A. Islet cell antibodies. Diabetic Med 1987; 4: 285-92. 18 Christie MR, Vohra G, Champagne P, Daneman D, Delovitch TL. Distinct 8 Johnston C, Alviggi L, Millward BA, Leslie RDG, Pyke DA, Vergani D. antibody specificities to a 64-kD islet cell antigen in type 1 diabetes as Alterations in T-lymphocyte subpopulations in type 1 diabetes: exploration revealed by trypsin treatment. J Exp Med 1990; 172: 789-94. ofgenetic influence in identical twins. Diabetes 1988; 37: 1484-8. 19 Bottazzo GF, Dean BM, McNally JM, Mackay EH, Swift PGF, Gamble R. In 9 Smerdon RA, Peakman M, Hussain MJ, et al. Increase in simultaneous co- situ characterization of autoimmune phenomena and expression of HLA expression of naive and memory markers at diagnosis of insulin dependent molecules in the pancreas in diabetic insulitis. NEnglJMed 1985; 313: 353- diabetes mellitus. Diabetes 1992; 42: 127-33. 60. 10 Alviggi L, Johnston C, Hoskins PJ, et al. Pathogenesis of insulin dependent 20 Peakman M, Vergani D. Cell-mediated immunity and type 1 diabetes. Diabetes diabetes: a role for activated T lymphocytes. Lancet 1984; ii: 4-5. Reviews 1992; 1: 5-8. 11 Peakman M, Hussain MJ, Millward BA, Leslie RDG, Vergani D. Effect of 21 De Berardinis P, Londei M, Kahan M, et al. The majority of the activated T initiation of insulin therapy on T-lymphocyte activation in type 1 (insulin cells in the blood ofinsulin-dependent diabetes mellitus (IDDM) patients are dependent) diabetes. Diabetic Med 1990; 7: 327-30. CD4+. Clin Exp Immunol 1988; 73: 255-9. 12 Roep BO, Aarden SD, De Vries RRP, Hutton JC. T-cell clones from a type-I 22 Leslie RDG, Tun RYM, Peakman M, et al. Persistent cellular and humoral diabetes patient respond to insulin secretory granule proteins. Nature 1990; immune changes in the prediabetic period: a prospective twin study. 345: 632-4. Diabetologia 1992; 35 (suppl 1): A32. 13 Roep BO, Kallan AA, Hazenbos WL, et al. T-cell reactivity to 38 kD insulin- 23 Peakman M, Alviggi L, Hussain MJ, Pyke DA, Leslie RDG, Vergani D. secretory granule protein in patients with recent-onset type 1 diabetes. Lancet Persistent T cell activation predicts diabetes in unaffected identical co-twins 1991; 337: 1439-41. of type 1 diabetics. Diabetologia 34 (suppl 2): A56. 14 Lendrum R, Walker GJ, Gamble DR. Islet cell antibodies in juvenile diabetes 24 Christie MR, Tun RYM, Lo SSS, et al. Antibodies to GAD and tryptic mellitus ofrecent onset. Lancet 1975; i: 880-3. fragments ofislet 64K antigen as distinct markers for development ofIDDM. 15 Greenbaum CJ, Palmer JP. Insulin antibodies and insulin autoantibodies. Diabetes 1992; 41: 782-7. Diabetic Med 1991; 8: 97-105. 25 Feldmann M, June CH, McMichael A, Maini R, Simpson E, Woody JN. T- 16 Baekkeskov S, Neilsen JH, Marner B, Bilde T, Ludvigsson J, Lernmark A. cell-targeted immunotherapy. Immunol Today 1992; 13: 84-5. Assessment ofpancreatic exocrine function Impairment of pancreatic exocrine function in childhood is simplified representation of their physiological role would be most commonly seen in association with cystic fibrosis but that secretin, released by acid in the duodenum, provides a occurs in a range of different disorders.' Function may be bicarbonate rich secretion, while cholecystokinin released by assessed by aspiration of duodenal juice and measurement of the products of protein and fat digestion stimulates the enzymes secreted by the gland in response to stimulation by production of a fluid rich in enzymes including trypsin, hormones or nutrients. Such stimulatory tests are intended to chymotrypsin, carboxypeptidase, pancreatic amylase, and or not the is abnormal Trypsin, released as inactive trypsinogen, changes define whether pancreas diseased, lipases. http://adc.bmj.com/ secretions implying abnormal pancreas. There is, however, spontaneously into its active form in solution, converting the no clear agreement on what constitutes abnormal results. other proteases into their active forms. This change is Among the indications for pancreatic function testing are accelerated both by enterokinase secreted by enterocytes of clinical suspicion of pancreatic insufficiency such as in the the proximal small intestine, and the presence of activated child with steatorrhoea and failure to thrive, the assessment trypsin.6 Pancreatic lipase is prevented from being denatured of enzyme replacement therapy in a child with known as a result of adsorption to the oil:water interface through pancreatic disease such as cystic fibrosis, and serial monitor- being anchored by a colipase, a small protein also secreted by on September 26, 2021 by guest. Protected copyright. ing of function for example after pancreatitis or partial the pancreas. pancreatectomy. Alternatives to duodenal intubation include During the test, secretin and cholecystokinin are given a number of indirect function tests. These are often easier to at an unphysiological dose of 2 units/kg body weight with perform and rely upon analysis of enzymes in faeces or the aim of exciting the maximal possible response in the serum or investigation of how completely an administered pancreas. Children in the first few months of life seem test substance is digested. Indirect tests are usually based on refractory to stimulation, probably because there are the assessment of a single specific pancreatic enzyme; it is insufficient numbers of secretagogue receptors or receptor not always appropriate to make assumptions about other affinity is low. The total volume of secretions, bicarbonate enzymes. For example, isolated enzyme deficiencies are well output, lipase and amylase activities are measured together recognised,23 and in newborns and young infants there with one or more proteases7 and expressed in terms of appears to be variation in the rates of development of output/kg body weight/50 minutes of test. A correction for individual pancreatic enzymes.4 In general, however, such incomplete juice recovery can be made if a non-absorbable tests when combined with clinical assessment are highly marker is perfused into the proximal duodenum and suitable for identifying those patients who require more aspirated distally.8 The validity of this test refinement which detailed study. As pancreatic insufficiency is relatively adds greatly to an already technically complex procedure has uncommon in childhood it is important that an indirect test not been clearly established. Enzyme analysis should be should reliably give a negative result in the absence of perfohned without delay, but addition of glycerol (50% v/v) disease. and storage at -20°C will stabilise lipase and trypsin for at least a month. Although reference ranges for stimulated duodenal juice have been published for children,7 problems Intraduodenal tests in standardising analysis of enzymes make comparisons PANCREOZYMIN-SECRETIN TEST between laboratories extremely difficult. Ideally, stimulation The standard intraduodenal test involves stimulation of the tests should only be performed in a centre with its own pancreas with intravenous cholecystokinin (pancreozymin) reference-ranges. Normal amylase and lipase activities with followed by secretin.' These specific intestinal peptides are low protease activity should suggest congenital enterokinase used because they provide a powerful stimulus and appear to deficiency.9 Addition ofenterokinase to a sample of duodenal be important in normal control of pancreatic function. A fluid causes a marked increase in tryptic activity. 100 Puntis MEAL TEST ally more difficult to achieve in plasma, so that an alternative A test meal of glucose, protein, and fat may be used to to urine collection is not yet available. provide a more physiological stimulus to pancreatic secre- Arch Dis Child: first published as 10.1136/adc.69.1.99 on 1 July 1993. Downloaded from tion. A two hour postprandial collection of duodenal fluid is made and bile salt concentration as well as enzyme activity FLUORESCEIN DILAURATE TEST per millilitre measured.'0 The test can therefore be used not Fluorescein dilaurate (pancreolauryl) is an alternative sub- only to detect pancreatic pathology but also to investigate strate to NBT-PABA, hydrolysed by pancreatic cholesterol other factors in the pathophysiology of steatorrhoea. Dis- ester hydrolase to produce lauric acid and fluorescein. The advantages include an appreciable technical failure rate, the latter is excreted in a 10 hour urine collection and can be need for a two hour collection, and the fact that bicarbonate assayed using spectrophotometry or fluorimetry. A second analysis is not possible. It is, however, simpler to perform day test withunesterified fluoresceinimproves test specificity, than hormonal stimulation and could be carried out in units as in the bentiromide/PABA
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