Comparison of orocaecal transit times assessed by the lactulose/breath hydrogen and the sulphasalazine/sulphapyridine methods.

The lactulose/breath hydrogen and the sulphasalazine/sulphapyridine methods of assessing orocaecal transit time have been compared. In a two part crossover study in healthy normal subjects the median orocaecal transit time by the SLZ/SP method was 4.84 hours but only 2.92 hours by the lactulose/breath hydrogen method. Coadministration of lactulose and sulphazalazine to nine subjects with assessment of orocaecal transit time by hydrogen breath determination and plasma sulphapyridine assay gave orocaecal transit times of 2.33 and 2.25 hours respectively suggesting that the lactulose reduces transit time and that the lactulose/breath hydrogen method, which is so convenient to use, gives artificially low transit times. A third experiment was undertaken to compare the orocaecal transit times after 1.5 and 3.0 g sulphazalazine. The orocaecal transit times after the two doses were not statistically different.     

Orocaecal transit time in health and in thyroid disease.

Altered bowel habit commonly occurs in thyroid disease. We measured orocaecal transit in healthy volunteers and in hyperthyroid and hypothyroid patients before and after treatment, using the lactulose hydrogen breath test incorporating a standard liquid meal to obtain a more physiological assessment. Mean transit time in 12 control subjects was 85 (8) minutes (mean (SE)) (mean coefficient of variation between replicate studies, 8.6% (3%)). In eighteen hyperthyroid patients transit was more rapid at 49 (4) minutes (p less than 0.01). Ten hypothyroid patients had a transit time similar to controls at 91 (9) minutes. Transit time returned to normal in thyrotoxic patients after treatment but in eight hypothyroid patients retested, it remained unchanged. Our findings suggest that (a) the inclusion of a liquid meal provides a reproducible method of measuring orocaecal transit using the lactulose hydrogen breath test, (b) rapid small bowel transit in thyrotoxicosis may be one factor in the diarrhoea which is a feature of the disease and (c) if altered gut transit is the cause of sluggish bowel habit in hypothyroidism, delay in the colon, and not small bowel, is likely to be responsible.     

Statistical analysis of the lactulose/breath hydrogen test in the measurement of orocaecal transit: its variability and predictive value in assessing drug action.

The variability in the orocaecal transit time as measured by the lactulose/breath hydrogen method has been studied for three conditions: lactulose given with a meal, subjects sitting; lactulose given with a meal, subjects semirecumbent; lactulose given in aqueous solution, subjects semirecumbent. Thirty three healthy subjects attended on up to 12 occasions. It was found that administration of the lactulose with a meal significantly reduced the variability (p less than 0.05) and that adoption of the semirecumbent position further reduced variability. A power analysis was used to predict the number of subjects who would be required to show a given percentage change in orocaecal transit time at specified probabilities and powers. A graph and a table for use in the prediction of subject numbers at a probability of 5% and for powers of 50-99% is presented. A dose response curve for metoclopramide using the lactulose/breath hydrogen method is given for doses of 10, 15, and 20 mg.     

Influence of orocaecal transit time on hydrogen excretion after carbohydrate malabsorption.

The aim of the present study was to determine whether changes in orocaecal transit time (OCTT) affect the magnitude of the breath hydrogen (H2) excretion after ingestion of unabsorbable carbohydrate. We studied eight healthy subjects by interval sampling of end expiratory H2 concentration for 12 hours after ingestion of: (1) 10 g lactulose (L); (2) 10 g L with 20 mg metoclopramide (M) as tablets; (3) 20 g L, and (4) 20 g L with 7.5 mg diphenoxylate (D) as tablets, in random order. In spite of significant changes in OCTT after M and D, there were no significant changes, compared for the same dose of lactulose, with respect to area under the breath H2 excretion curves, peak increments of H2 concentration or timing of the peak increment. We conclude that, within the ranges observed, the OCTT does not significantly affect the shape of the H2 concentration versus time curves. In comparative studies estimates of the degree of carbohydrate malabsorption on the basis of breath H2 concentration may be valid in spite of differences in OCTT.     

Reproducible lactulose hydrogen breath test as a measure of mouth-to-cecum transit time

Breath hydrogen monitoring after oral lactulose syrup is a conventional measure of mouth-to-cecum transit time (MCTT), but its reproducibility has been questioned. We compared the reproducibility of five measurements of MCTT after a conventional breakfast (380 kcal) taken with tea containing 20 g lactulose to five measurements of MCTT after 20 g lactulose in water in eight normal volunteers. Individual mean breakfast transit time was not significantly different from lactulose transit time in each of the seven subjects, but one had a breakfast transit time of 151±15 min and a lactulose transit time of 86±22 minutes (¯X ±sd, P<0.001). The coefficient of variation of breakfast transit time (11.6±5.3%, range: 6.9–24.2%) was less than that of lactulose transit time (30.7±7.8%, range: 22.1–50.0%, P<0.001). In a second set of experiments, the liquid phase marker ( ^99m Technetiumdiethylene triamine pentaacetic acid) emptied from the stomach more rapidly after the lactulose solution (T1/2 16.3±5.4) than after the breakfast (33.9±10.9 min, P<0.01) and MCTT was shorter after lactulose (77±32 vs 104±40 min, trespectively, P<0.05). There was no correlation between MCTT of lactulose and breakfast and between half-time gastric emptying and MCTT of either lactulose or breakfast. We conclude that the ingestion of inert lactulose induces an abnormally rapid MCTT and that breakfast MCTT is a much more reproducible investigation and should be employed in studies requiring serial measurements.     

Relations between transit time, fermentation products, and hydrogen consuming flora in healthy humans.

BACKGROUND/AIMS: To investigate whether transit time could influence H2 consuming flora and certain indices of colonic bacterial fermentation. METHODS: Eight healthy volunteers (four methane excretors and four non-methane excretors) were studied for three, three week periods during which they received a controlled diet alone (control period), and then the same diet with cisapride or loperamide. At the end of each period, mean transit time (MTT) was estimated, an H2 lactulose breath test was performed, and stools were analysed. RESULTS: In the control period, transit time was inversely related to faecal weight, sulphate reducing bacteria counts, concentrations of total short chain fatty acids (SCFAs), propionic and butyric acids, and H2 excreted in breath after lactulose ingestion. Conversely, transit time was positively related to faecal pH and tended to be related to methanogen counts. Methanogenic bacteria counts were inversely related to those of sulphate reducing bacteria and methane excretors had slower MTT and lower sulphate reducing bacteria counts than non-methane excretors. Compared with the control period, MTT was significantly shortened (p < 0.05) by cisapride and prolonged (p < 0.05) by loperamide (73 (11) hours, 47 (5) hours and 147 (12) hours for control, cisapride, and loperamide, respectively, mean (SD)). Cisapride reduced transit time was associated with (a) a significant rise in faecal weight, sulphate reducing bacteria, concentrations of total SCFAs, and propionic and butyric acids and breath H2 as well as (b) a significant fall in faecal pH and breath CH4 excretion, and (c) a non-significant decrease in the counts of methanogenic bacteria. Reverse relations were roughly the same during the loperamide period including a significant rise in the counts of methanogenic bacteria and a significant fall in those of sulphate reducing bacteria. CONCLUSIONS: Transit time differences between healthy volunteers are associated with differences in H2 consuming flora and certain indices of colonic fermentation. Considering the effects of some fermentation products on intestinal morphology and function, these variations may be relevant to the pathogenesis of colorectal diseases.     

In vivo influence of nicotine on human basal and NSAID-induced gut barrier function

BACKGROUND: Smoking reduces the non-steroidal anti-inflammatory drug (NSAID)-induced small intestinal permeability increase in healthy people. It also affects inflammatory bowel disease that is associated with a disturbed gut barrier function. To assess the role of nicotine on barrier function, its influence on basal and NSAID-induced intestinal permeability was studied in healthy volunteers. METHODS: Thirty-one healthy non-smoker subjects performed permeability tests with 51Cr-EDTA and sugar markers (sucrose, lactulose, mannitol, sucralose) before and during 2 weeks of nicotine patch application, and with and without indomethacin intake, respectively. Since smoking has been described as affecting motility, transit measurements were also done with the sodium[13C]-octanoate and lactose-[13C]-ureide breath tests before and during nicotine exposure. Correlations between permeability markers were checked and the influence of gastrointestinal transit was assessed. RESULTS: Nicotine did not affect barrier function in vivo, nor gastric emptying, small-bowel transit time or orocaecal transit. 51Cr-EDTA and lactulose correlated in basal 0-6 h permeability testing (r = 0.529, P < 0.0001), as did 6-24 h excretion of 51Cr-EDTA and sucralose (r = 0.474, P < 0.001); 97% and 90% of the subjects had a permeability increase after indomethacin intake for 0-6 h and 6-24 h excretion of Cr-EDTA, respectively. This population proportion is 63% for lactulose/mannitol and 83% for sucralose. CONCLUSIONS: Short-term exposure to nicotine does not alter normal basal or NSAID-induced gut barrier function or transit. 51Cr-EDTA and the respective sugar markers correlate well in in vivo permeability testing in healthy humans. The radioactive test detects more NSAID-induced permeability increase than does the lactulose/mannitol ratio permeability test.     

Role of fasting gastrointestinal motility in the variability of gastrointestinal transit time assessed by hydrogen breath test.

Gastrointestinal motility and transit time, measured by the hydrogen breath test, were simultaneously assessed in six healthy volunteers. Each subject underwent six studies on separate days. On each day motility was measured in the gastric antrum, duodenum, and proximal jejunum and 15 g of lactulose was given either by mouth during gastric phases I, II, III of the motor migrating complex or infused duodenally during duodenal phases I, II, III, one phase being studied each day in random order. Fasting activity was not interrupted by the lactulose. The lactulose transit time decreased significantly from a peak with phase I through phase II to a minimum with phase III (mean (SD) 155 (26) min v 120 (10) min v 94 (14) min, p less than 0.001). Similar results were noted when the lactulose was instilled intraduodenally (156 (23) min v 125 (19) min v 100 (17) min, p less than 0.001). No correlation was found between motility index and transit. These results suggest that different phases of fasting gastrointestinal motility are major determinants of the transit time estimated by the hydrogen breath test and explain the variability of this test in practice.     

Hydrogen Breath Test Assessment of Orocecal Transit Time; Comparison with Barium Meal Study

Orocecal transit time was measured simultaneously by the hydrogen breath test and a barium meal study in 12 hospitalized patients, the objective being to determine whether the former test accurately represents the orocecal transit time, and to establish an adequate criterion for the transit time, based on the former test. Two definitions of orocecal transit time by the hydrogen breath test were evaluated: the time from lactulose ingestion to a sustained increase of over 5 ppm above fasting levels in the end-expiratory hydrogen concentration (definition A) and the interval to that of over 10 ppm (definition B). The orocecal transit time measured by the radiologic method was 63 +/- 9 min (mean +/- SEM), whereas that using definition A of the hydrogen breath test was 74 +/- 9 min, and that using definition B was 87 +/- 10 min. Transit times determined by both definitions closely correlated with that obtained by the radiologic method (A, r = 0.86, p less than 0.01; B, r = 0.81, p less than 0.01). Therefore, elevation of end-expiratory hydrogen concentrations seemed to coincide with cecal appearance of the head of the lactulose load. When the mean transit times were compared with findings in case of the radiologic method, definition A rather than B appeared to be more appropriate to determine orocecal transit time.     

Blood glucose response after oral intake of lactulose in healthy volunteers: A randomized,controlled, cross-over study

AIM To investigate possible changes of blood glucose levels after oral intake of lactulose in healthy subjects.METHODS The study was performed as prospective, randomized, two-part study with 4-way cross-over design with n = 12 in each study arm. Capillary blood glucose levels were determined over a time period of 180 min after intake of a single dose of 10 g or 20 g lactulose provided as crystal or liquid formulation. During the manufacturing process of lactulose, impurities with sugars(e.g., lactose, fructose, galactose) occur. Water and 20 g glucose were used as control and reference. Because lactulose is used as a functional food ingredient, it may also be consumed by people with impaired glucose tolerance, including diabetics. Therefore, it is of interest to determine whether the described carbohydrate impurities may increase blood glucose levels after ingestion. RESULTS The blood glucose concentration-time curves after intake of 10 g lactulose, 20 g lactulose, and water were almost identical. None of the three applications showed any changes in blood glucose levels. After intake of 20 g glucose, blood glucose concentration increased by approximately 3 mmol/L(mean Cmax = 8.3 mmol/L), reaching maximum levels after approximately 30 min and returning to baseline within approximately 90 min, which was significantly different to the corresponding 20 g lactulose formulations(P 0.0001). Comparing the two lactulose formulations, crystals and liquid, in the dosage of 10 g and 20 g, there was no difference in the blood glucose profile and calculated pharmacokinetic parameters despite the different amounts of carbohydrate impurities(1.5% for crystals and 26.45% for liquid). Anyhow, the absolute amount of single sugars was low with 0.3 g in crystals and 5.29 g in liquid formulation in the 20 g dosages. Lactulose was well tolerated by most volunteers, and only some reported mild to moderate mainly gastrointestinal side effects. CONCLUSION The unchanged blood glucose levels after lactulose intake in healthy subjects suggest its safe use in subjects with impaired glucose tolerance.     

Gastrointestinal transit time in human pregnancy: prolongation in the second and third trimesters followed by postpartum normalization

Fifty-nine studies of gastrointestinal transit time were performed in 27 healthy women during pregnancy and postpartum. Gastrointestinal transit time was defined as the time of the first sustained rise in breath hydrogen concentration after ingestion of 10 g of lactulose. Gastrointestinal transit time was significantly prolonged in both the second and third trimesters of pregnancy (125 +/- 48 min and 137 +/- 58 min, respectively) when compared with either the first trimester of pregnancy or the postpartum period (99 +/- 39 min and 75 +/- 33 min, respectively). Transit times measured in the first trimester were not significantly different from those postpartum. Because the prolongation of transit time in late pregnancy is transient, it is probably due to hormones (perhaps progesterone) or other metabolic effects of pregnancy.     

Effect of ageing on the gastro-intestinal transit of a lactulose-supplemented mixed solid-liquid meal in humans

Gastro-intestinal transit of a mixed solid-liquid meal containing wheat bread, scrambled eggs, coffee labelled with 99mTc, orange juice with lactulose and indigocarmine was evaluated in 21 young control (mean age 33.5 years) and 25 elderly subjects (mean age 81.7 years) without gastrointestinal complaints or severe medical illness. The rate of gastric emptying was determined by an anterior gamma camera technique, mouth-to-caecum transit by the hydrogen breath test and whole-gut transit by the first stool passage of indigocarmine. Gastric emptying was significantly prolonged in older subjects: t1/2 = 136 +/- (SEM) 13 versus 81 +/- 4 min; p less than 0.001. Concerning mouth-to-caecum or whole-gut transit time, significant differences between the two study groups were not detected.     

Scintigraphic demonstration of lactulose-induced accelerated proximal colon transit.

Although lactulose, a widely used cathartic, is known to increase stool frequency, details of its site of action in the colon are obscure. In the present study a noninvasive scintigraphic technique was used to closely follow the movements of proximal colonic contents. Lactulose, 10-20 mL three times daily, significantly accelerated mean transit through the ascending colon from 12.9 +/- 3.7 to 7.0 +/- 2.5 hours (n = 11; P less than 0.01). This was associated with the occurrence of mass movements, with six such events seen during lactulose treatment whereas only one was seen during the control study (P less than 0.05). Lactulose also accelerated movement through the rest of the colon so that at 24 hours after dosing the geometric center of the isotope bolus was distal to that seen during the control study (6.6 +/- 1.2 vs. 4.7 +/- 1.3; n = 11, P less than 0.001). This model of diarrhea in otherwise normal subjects was subsequently used to study the effects of viscous gels in diarrhea. The viscous and relatively poorly fermented gel ispaghula, 3.5 g three times daily, abolished mass movements and was associated with a small but significant increase in proximal colonic transit time, which increased from 6.1 +/- 2.1 to 7.7 +/- 1.5 hours (n = 8; P less than 0.05). By contrast, the viscous but readily fermentable gelling agent guar gum, 5 g three times daily, further accelerated the cathartic effect of lactulose, with the mean transit time decreasing from 6.4 +/- 2.3 to 4.7 +/- 1.7 hours (n = 8; P less than 0.05). The acceleration of proximal colonic transit by lactulose may be a useful model to study diarrhea and its modification by therapy.     

Relationships between symptoms, menstrual cycle and orocaecal transit in normal and constipated women.

Because severe constipation is a disorder largely confined to young women, the possibility that menstrually related factors contribute to disturbed gastrointestinal motor function has been raised. It has also been reported that normal menstruating women show changes in upper gut transit between the follicular and luteal phases of the menstrual cycle and that patients with constipation show prolonged transit. We therefore studied relationships between symptom severity and orocaecal transit during the menstrual cycle in a group of 14 constipated women and a series of control groups comprising seven normal menstruating women, five postmenopausal women, and eight normal men, to determine whether phases of the menstrual cycle were associated with alteration in symptoms or transit. A regular menstrual cycle was reported by 13 of the 14 patients (range 26-30 days) and by all the menstruating female volunteers. Seven patients noted variation in constipation during the menstrual cycle, in all cases this comprised an improvement in symptoms just before or during menstruation. No consistent relationship between symptom severity and follicular or luteal phase was noted. Repeated orocaecal transit measurements in the four study groups showed no consistent differences (greater than 0.05) between groups or during the menstrual cycle (mean change weeks 1-4, -10 +/- 20 min). These findings are inconsistent with the hypothesis of a progesterone related effect upon orocaecal transit in either normal or constipated women.     

Milk is a useful test meal for measurement of small bowel transit time

To improve and standardize the measurement of small bowel transit time, milk was employed for the test meal instead of the conventional lactulose meal. Although 92% of the subjects were lactase deficient, only 2% were milk intolerant and 13% were lactose intolerant. Small bowel transit time with milk (milk breath hydrogen test) was 113±9 min (mean ± SE,n=20); the normal range calculated from the mean ±2 SD was 31–195 min. The coefficient of variation in the milk hydrogen breath test was 13 ± 4% (n=6), whereas in the lactulose hydrogen breath test, it was 39±16% (n=10). The frequency of non-hydrogen producers, the occurrence of discomfort, and the reproducibility were better, though not significantly so, in the milk hydrogen breath test than in the lactulose. Since lactase activity in the intestine is variable in lactase-deficient subjects, small bowel transit times for milk may change from subject to subject. However, individual reproducibility of the milk hydrogen breath test is good. It could be useful for pharmacological experiments using paired comparison, for screening tests, or for the follow up of diseases in which small bowel transit time is affected.     

The effect of chilli on gastrointestinal transit

The effects of chilli on gastrointestinal transit (gastric emptying, orocaecal transit, whole gut transit) were evaluated in eight healthy volunteers. In each subject, gastrointestinal transit of a standard test meal was measured on two separate days. On one of these occasions, 20 g of chilli powder was added to the meal. Gastric emptying was quantified with a radioisotopic technique, orocaecal transit by measurement of breath hydrogen concentrations and whole gut transit by counting the number of radio-opaque markers in the stool. The rate of gastric emptying was slower (P less than 0.05) and whole gut transit was faster (P less than 0.02) after the meal containing chilli, compared with the other meal. There was no significant difference in orocaecal transit. These results show that ingestion of chilli is associated with significant effects on gastric emptying and intestinal transit.     

Lactulose hydrogen breath test in orocecal transit assessment

Orocecal transit time can be studied easily using the hydrogen breath test with lactulose, but the method has some important limitations. The orocecal transit time of 10 patients suffering from irritable bowel syndrome was measured twice, at a one-week interval, by breath test and scintigraphy simultaneously using an aqueous solution of 20 g lactulose containing 74 MBq of [^99mTc]DTPA. Abdominal radioactivity and alveolar hydrogen values obtained every 5 min were noted and used to obtain the following: orocecal transit time by the two methods; ileocecal lactulose flow; total and per gram of lactulose hydrogen production; mean hydrogen concentration during the right colon filling; and measurement error of the breath test with respect to the scintigraphy. In the case of the breath test, the orocecal transit time intrapatient reproducibility was better (coefficient of variation =13.5%) when a hydrogen threshold increment of 5 ppm was used; the best correlation with the scintigraphic measurement was observed at this threshold (r=0.90,P<0.001). The breath test overestimated orocecal transit time with the error correlating negatively and significantly with the total hydrogen production and, particularly, the mean hydrogen concentration (r=0.79,P<0.01): for a mean hydrogen concentration of more than 15 ppm, the error was negligible, while within this value there was a noticeable overestimation. To conclude, the lactulose hydrogen breath test is capable of giving an accurate measurement of orocecal transit time if a hydrogen threshold increment of 5 ppm is chosen and if the mean hydrogen concentration in the first 30 min of the right colon filling is taken into account.     

Effects of a serotonin 5-HT(4) receptor antagonist SB-207266 on gastrointestinal motor and sensory function in humans

BACKGROUND: Serotonin 5-HT(4) receptors are located on enteric cholinergic neurones and may regulate peristalsis. 5-HT(4) receptors on primary afferent neurones have been postulated to modulate visceral sensation. While 5-HT(4) agonists are used as prokinetic agents, the physiological role of 5-HT(4) receptors in the human gut is unknown. AIMS: Our aim was to characterise the role of 5-HT(4) receptors in regulating gastrointestinal motor and sensory function in healthy subjects under baseline and stimulated conditions with a 5-HT(4) receptor antagonist. METHODS: Part A compared the effects of placebo to four doses of a 5-HT(4) receptor antagonist (SB-207266) on the cisapride mediated increase in plasma aldosterone (a 5-HT(4) mediated response) and orocaecal transit in 18 subjects. In part B, 52 healthy subjects received placebo, or 0.05, 0.5, or 5 mg of SB-207266 for 10-12 days; gastric, small bowel, and colonic transit were measured by scintigraphy on days 7-9, and fasting and postprandial colonic motor function, compliance, and sensation during distensions were assessed on day 12. RESULTS: Part A: 0.5, 5, and 20 mg doses of SB-207266 had significant and quantitatively similar effects, antagonising the cisapride mediated increase in plasma aldosterone and acceleration of orocaecal transit. Part B: SB-207266 tended to delay colonic transit (geometric centre of isotope at 24 (p=0.06) and 48 hours (p=0.08)), but did not have dose related effects on transit, fasting or postprandial colonic motor activity, compliance, or sensation. CONCLUSION: 5-HT(4) receptors are involved in the regulation of cisapride stimulated orocaecal transit; SB 207266 tends to modulate colonic transit but not sensory functions or compliance in healthy human subjects.     

Assessment of the reproducibility of the lactulose H2 breath test as a measure of mouth to caecum transit time

The lactulose H2 breath test is in use as a simple non-invasive measurement of mouth to caecum transit time, but its reproducibility has never been assessed. We have examined the reproducibility of mouth to caecum transit time in 21 normal subjects using lactulose 10, 15, and 20 g; seven subjects being studied with 10 g and 12 each with 15 and 20 g doses. Transit time decreased with increasing doses of lactulose although the differences were not significant between or within (n = 5) individuals. Variation in transit times between individuals was considerable with all doses of lactulose (mean coefficient of variation of 18.5, 29.7 and 28.3% with 10, 15, and 20 g respectively). The addition of lactulose to a liquid meal containing carbohydrate, fat, and protein decreased the coefficient of variation to less than 10% in four subjects studied. The lactulose H2 breath test could be made more reproducible by including a liquid meal.     

The effect of thyroxine on small intestinal motility in the elderly

OBJECTIVE: To study the effects of thyroxine on orocaecal transit time in a group of elderly hypothyroid patients on long-term thyroxine replacement therapy. DESIGN: Measurement of the effect of withdrawal and subsequent replacement of thyroxine replacement therapy on orocaecal transit time. PATIENTS: Fifteen elderly, previously hypothyroid patients on full replacement therapy with oral thyroxine were studied. There were 11 females and four males, aged 60-94 years (median 78 years) receiving initially 50-200 micrograms of oral thyroxine daily (median 100 micrograms). MEASUREMENTS: Serum TSH and FT4 were measured by radioimmunoassay and orocaecal transit time assessed using a lactulose hydrogen breath test. These tests were repeated 7 days after withdrawal of thyroxine replacement and again 7 days after subsequent reinstatement of therapy. RESULTS: On withdrawal of therapy, the median transit time increased from 75.0 to 135 minutes (P less than 0.01), the median TSH increased from 1.8 to 2.3 mU/l (P = NS) and the median FT4 decreased from 13.7 to 10.6 pmol/l (P less than 0.01). On reinstatement of therapy, the median transit time decreased to 95 minutes (P = NS), the median TSH decreased to 1.1 mU/l (P = NS) and the median FT4 increased to 14.1 pmol/l (P less than 0.01). CONCLUSIONS: These findings demonstrate the sensitivity of the small bowel to changes in thyroid hormone status and suggest that constipation arising as a result of this hypomotility may well be an early physical manifestation of hypothyroidism.