Saturday 15 April 1978 GUT-HORMONEDISEASE PROFILE IN CŒLIAC
eased bowel. We have therefore compared the release of upper small-intestinal hormones with the release of hor-
produced in other parts of the gut in with untreated and treated cceliac disease. mones
H. S. BESTERMAN D. L. SARSON
D. I. JOHNSTON* J. S. STEWART S. GUERIN
S. R. BLOOM A. M. BLACKBURN H. R. PATEL† R. MODIGLIANI C. N. MALLINSON
Royal Postgraduate Medical School, London W12, Department of Pœdiatrics, King’s College Hospital,
Patients and Methods Permission was obtained from the relevant ethical committees and informed consent was obtained from all adults and from the parents of all the children involved.
Intraduodenal Acid
London SE5, West Middlesex Hospital, Isleworth, Middlesex; Inserm U54, Hopital Saint-Lazare, Paris; and Greenwich District Hospital, London SE10
Patients with cœliac disease have a highly significant reduction in the release of secretin and gastric inhibitory polypeptide from the upper small intestine, but a greatly increased release of enteroglucagon, and also of neurotensin, from the lower part of the small intestine. The release of gastrin and pancreatic polypeptide, from the antrum and pancreas respectively, is, however, normal. Thus the pattern of hormone release reflects the location of the mucosal lesion. The gut-hormone profile may also help to characterise other gastrointestinal diseases.
Summary
Introduction THE treatment of coeliac disease is well established
but, despite apparently strict adherence to a gluten-free diet, normality is not always achieved. Another problem with coeliac disease is that many cases are not diagnosed until late and may first present with serious
patients
com-
plications.2 The pathophysiology of coeliac disease is still not fully understood. The mucosal architecture, predominantly that in the proximal small intestine, is abnormal and is associated with an increase in enterocyte turnover.3 A compensatory increase in ileal absorption of a wide variety of substances, including glucose, water, sodium,4-7 methionine,8 and vitamin B129’10 has also been reported but the mechanism for this is unknown. In addition, there is a failure of pancreatic exocrine function; although the response to exogenous secretin and cholecystokinin is normal, intraduodenal acid and aminoacid perfusions are followed by a considerably reduced pancreatic bicarbonate" and enzyme secretion.12.13 It has been suggested that these abnormalities are due to a failure of release of the relevant gut hormones from the dis*Present address: Nottingham Children’s Hospital, Nottingham. †Present address: Joyce Green Hospital, Dartford, Kent.
Secretin response to the instillation into the 3rd part of the duodenum of 0.5 mol/1 citric acid (5 ml/kg given over 10 minutes via a Crosby capsule) was measured in three groups of children; blood-samples were taken via a small indwelling catheter (inserted as part of the routine Crosby capsule biopsy procedure). The three groups were: (a) 6 children, aged 1-11 years, weighing below the 3rd percentile, who had total or partial villous atrophy diagnosed as cceliac disease after improvement on a gluten-free diet. (b) 6 children, aged 2-14 years, weighing between the 3rd and 10th percentile, who had been treated with a strict gluten-free diet for at least 6 months with significant improvement in villous architecture. (c) 15 children, aged 1-14 years, weighing below the 3rd percentile, who were being investigated for short stature, but who were found to have normal jejunal histology.
Test-meal The release of other gut hormones in response to a standard test-breakfast of 2 medium-sized boiled eggs, 60 g toast (gluten-free if appropriate), 10 g butter, 35 g marmalade, and 150 ml unsweetened orange juice (containing a total of 18 g protein, 22 g fat, and 66 g carbohydrate, equivalent to 530 calories) was studied in the following groups. (a) Untreated caeliac disease: 11 patients (4-male and 7 female), with a mean age of 45 (range 29-74) years and an average weight of 88% of ideal, who had either subtotal or severe partial atrophy which improved after a gluten-free diet. (b) Treated cceliac disease: 13 patients (4 male and 7 female) with a mean age of 44 (range 23-69) years and an average weight of 93% of ideal, who had biopsy-proven coeliac disease and who had adhered strictly to a gluten-free diet for at least six months; all had had a good clinical, hasmatological, and histological response to the diet. (c) Healthy controls: 13 subjects (4 male and 9 female) with a mean age of 42 (range 23-59) years and an average weight of 101% of ideal; none had a present or past history of gastrointestinal disease. Blood-samples for hormone assays were taken into heparinised tubes and 400 kallidinogenase-inactivating units of aprotinin (’Trasylol’) per ml was added. Plasma was separated within 15 minutes of sampling and stored at -20°C until assay. Hormone radioimmunoassays were carried out by conventional methods with antisera raised to pure natural human gastrin 14 and pancreatic polypeptide,l5 to porcine secretin,16 8068
786
gastric inhibitory polypeptide (G.I.p.),17 and glucagon,’8 and to bovine insulin and neurotensin.19 The assays could detect the following plasma changes with 95% confidence: secretin 1.55 pmol/l; gastrin 2 pmul/1; pancreatic polypeptide 4 pmol/1; G.i.p. 8 pmol/1; enteroglucagon 10 pmol/l; insulin 6 pmol/l; neurotensin 5 pmol/1. No cross-reaction was’ detectable between any of the peptides assayed.
Results
Basal (fasting) concentrations, maximum concentrations attained after the appropriate stimulus, total integrated release for each hormone, and blood-glucose are given in the accompanying table. Secretin
After intraduodenal citric acid, there was a significant rise in plasma secretin to 27.6±5 pmol/1 at 7.5minutes in children with normal jejunal mucosa (fig. 1). Levels were still raised at 10 minutes (24-7±3.5 pmol/1) after which they fell towards basal values. Children with untreated cceliac disease had a significantly smaller rise to 6.3±1-2 pmol/1 at 10 minutes (P
eased bowel. We have therefore compared the release of upper small-intestinal hormones with the release of hor-
produced in other parts of the gut in with untreated and treated cceliac disease. mones
H. S. BESTERMAN D. L. SARSON
D. I. JOHNSTON* J. S. STEWART S. GUERIN
S. R. BLOOM A. M. BLACKBURN H. R. PATEL† R. MODIGLIANI C. N. MALLINSON
Royal Postgraduate Medical School, London W12, Department of Pœdiatrics, King’s College Hospital,
Patients and Methods Permission was obtained from the relevant ethical committees and informed consent was obtained from all adults and from the parents of all the children involved.
Intraduodenal Acid
London SE5, West Middlesex Hospital, Isleworth, Middlesex; Inserm U54, Hopital Saint-Lazare, Paris; and Greenwich District Hospital, London SE10
Patients with cœliac disease have a highly significant reduction in the release of secretin and gastric inhibitory polypeptide from the upper small intestine, but a greatly increased release of enteroglucagon, and also of neurotensin, from the lower part of the small intestine. The release of gastrin and pancreatic polypeptide, from the antrum and pancreas respectively, is, however, normal. Thus the pattern of hormone release reflects the location of the mucosal lesion. The gut-hormone profile may also help to characterise other gastrointestinal diseases.
Summary
Introduction THE treatment of coeliac disease is well established
but, despite apparently strict adherence to a gluten-free diet, normality is not always achieved. Another problem with coeliac disease is that many cases are not diagnosed until late and may first present with serious
patients
com-
plications.2 The pathophysiology of coeliac disease is still not fully understood. The mucosal architecture, predominantly that in the proximal small intestine, is abnormal and is associated with an increase in enterocyte turnover.3 A compensatory increase in ileal absorption of a wide variety of substances, including glucose, water, sodium,4-7 methionine,8 and vitamin B129’10 has also been reported but the mechanism for this is unknown. In addition, there is a failure of pancreatic exocrine function; although the response to exogenous secretin and cholecystokinin is normal, intraduodenal acid and aminoacid perfusions are followed by a considerably reduced pancreatic bicarbonate" and enzyme secretion.12.13 It has been suggested that these abnormalities are due to a failure of release of the relevant gut hormones from the dis*Present address: Nottingham Children’s Hospital, Nottingham. †Present address: Joyce Green Hospital, Dartford, Kent.
Secretin response to the instillation into the 3rd part of the duodenum of 0.5 mol/1 citric acid (5 ml/kg given over 10 minutes via a Crosby capsule) was measured in three groups of children; blood-samples were taken via a small indwelling catheter (inserted as part of the routine Crosby capsule biopsy procedure). The three groups were: (a) 6 children, aged 1-11 years, weighing below the 3rd percentile, who had total or partial villous atrophy diagnosed as cceliac disease after improvement on a gluten-free diet. (b) 6 children, aged 2-14 years, weighing between the 3rd and 10th percentile, who had been treated with a strict gluten-free diet for at least 6 months with significant improvement in villous architecture. (c) 15 children, aged 1-14 years, weighing below the 3rd percentile, who were being investigated for short stature, but who were found to have normal jejunal histology.
Test-meal The release of other gut hormones in response to a standard test-breakfast of 2 medium-sized boiled eggs, 60 g toast (gluten-free if appropriate), 10 g butter, 35 g marmalade, and 150 ml unsweetened orange juice (containing a total of 18 g protein, 22 g fat, and 66 g carbohydrate, equivalent to 530 calories) was studied in the following groups. (a) Untreated caeliac disease: 11 patients (4-male and 7 female), with a mean age of 45 (range 29-74) years and an average weight of 88% of ideal, who had either subtotal or severe partial atrophy which improved after a gluten-free diet. (b) Treated cceliac disease: 13 patients (4 male and 7 female) with a mean age of 44 (range 23-69) years and an average weight of 93% of ideal, who had biopsy-proven coeliac disease and who had adhered strictly to a gluten-free diet for at least six months; all had had a good clinical, hasmatological, and histological response to the diet. (c) Healthy controls: 13 subjects (4 male and 9 female) with a mean age of 42 (range 23-59) years and an average weight of 101% of ideal; none had a present or past history of gastrointestinal disease. Blood-samples for hormone assays were taken into heparinised tubes and 400 kallidinogenase-inactivating units of aprotinin (’Trasylol’) per ml was added. Plasma was separated within 15 minutes of sampling and stored at -20°C until assay. Hormone radioimmunoassays were carried out by conventional methods with antisera raised to pure natural human gastrin 14 and pancreatic polypeptide,l5 to porcine secretin,16 8068
786
gastric inhibitory polypeptide (G.I.p.),17 and glucagon,’8 and to bovine insulin and neurotensin.19 The assays could detect the following plasma changes with 95% confidence: secretin 1.55 pmol/l; gastrin 2 pmul/1; pancreatic polypeptide 4 pmol/1; G.i.p. 8 pmol/1; enteroglucagon 10 pmol/l; insulin 6 pmol/l; neurotensin 5 pmol/1. No cross-reaction was’ detectable between any of the peptides assayed.
Results
Basal (fasting) concentrations, maximum concentrations attained after the appropriate stimulus, total integrated release for each hormone, and blood-glucose are given in the accompanying table. Secretin
After intraduodenal citric acid, there was a significant rise in plasma secretin to 27.6±5 pmol/1 at 7.5minutes in children with normal jejunal mucosa (fig. 1). Levels were still raised at 10 minutes (24-7±3.5 pmol/1) after which they fell towards basal values. Children with untreated cceliac disease had a significantly smaller rise to 6.3±1-2 pmol/1 at 10 minutes (P
