C. Gebbia

Serological markers for coeliac disease: is it time to change?

BACKGROUND Anti-gliadin and anti-endomysium antibodies are useful markers in the screening and follow-up of coeliac disease. The recent finding that tissue transglutaminase is the main auto-antigen of anti-endomysium has led to the discovery of anti-tissue transglutaminase antibodies. AIM To compare, in a prospective study, the diagnostic accuracy of anti-tissue transglutaminase, anti-gliadin and anti-endomysium antibodies in a large series of adult patients. METHODS The study involved 80 consecutive subjects undergoing upper gastrointestinal tract endoscopy for suspected coeliac disease (subsequently confirmed in 40 cases), 195 coeliac patients on a gluten-free diet, and 70 patients with different gastrointestinal disor ders and normal duodenal histology. Anti-gliadin, anti-endomysium and anti-tissue transglutaminase antibodies levels were measured using commercial kits. RESULTS The diagnostic sensitivity and specificity of anti-gliadin, anti-endomysium and anti-tissue transglutaminase antibodies were, respectively, 95% and 89.1%, 100% and 97.3%, and 100% and 98.2%: the agreement between the markers was substantial or almost perfect. In terms of follow-up, the positivity of the markers varied according to the strict adherence to, and duration of the gluten-free diet; the agreement between antiendomysium and anti-tissue transglutaminase antibodies was almost perfect. CONCLUSIONS Anti-endomysium and anti-tissue transglutaminase antibodies are both highly efficient for routine laboratory screening: the choice of one or the other will depend on the available facilities. However, neither can replace intestinal biopsy for general population screening because, in this case, their respective positive predictive values are only 15.7% and 21.8%. During follow-up, anti-gliadin retain their value as an early predictor of gluten ingestion.

Circulating ghrelin levels in celiac patients

OBJECTIVE:Ghrelin, the gut–brain peptide, recently identified as the natural endogenous ligand for growth hormone secretagogue receptors, exerts various endocrine and nonendocrine effects, including the control of energy homeostasis and food intake, but its possible relevance in malabsorption syndromes is unknown. Therefore, the aim of this study was to evaluate circulating ghrelin levels in adults with untreated and treated celiac disease (CD) and, for comparison, in healthy subjects.METHODS:Fasting serum ghrelin levels were measured in 30 consecutive patients with newly diagnosed CD, 13 celiac patients successfully treated with a gluten-free diet (GFD), and 30 healthy controls.RESULTS:Ghrelin levels were abnormally high in patients with active CD compared with controls (297 ± 17.6 vs 218 ± 15.2 pmol/L, p < 0.01) and correlated positively with intestinal mucosal lesion severity (rs= 0.444, p < 0.02). In the successfully GFD-treated patients, ghrelin values were normal compared with controls (233 ± 22.0 vs 218 ± 15.2 pmol/L, ns) and, moreover, correlated negatively with body mass index (r=−0.632, p = 0.02), unlike in the untreated patient group (r=−0.263, ns).CONCLUSION:High ghrelin levels characterized our series of adult patients with newly diagnosed CD and correlated significantly with the degree of severity of intestinal mucosal lesions. This is the first evidence of a relationship between ghrelin and inflammatory processes, but the mechanisms involved are still unclear. Furthermore, our findings suggest that an interplay of hormonal, metabolic, and nutritional factors could influence ghrelin secretion under pathophysiological circumstances.

The physical state of a meal affects hormone release and postprandial thermogenesis

There is evidence that food consistency may influence postprandial physiological responses. Recently we found that homogenization of a vegetable-rich meal significantly delayed the gastric emptying rate and was more satiating than the same meal in solid-liquid form. In this present study we investigated whether homogenization also influences endocrine and metabolic responses to the meal. Eight healthy men, aged 21-28 (mean 24.5) years, were given the meal (cooked vegetables 250 g, cheese 35 g, croutons 50 g and olive oil 25 g, with water 300 ml; total energy 2.6 MJ) in both solid-liquid (SM) and homogenized (HM) form, in random order, at 1-week intervals. Variables assayed were plasma glucose, insulin and glucose-dependent insulinotropic peptide (GIP) levels for 2 h and diet-induced thermogenesis (DIT) for 5 h. Plasma glucose pattern was similar after both meals. However, HM induced significantly greater insulin, GIP and DIT responses than SM. Mean integrated areas under the curves (AUC) were 1.7 (SEM 0.38) v. 1.2 (SEM 0.33) U/l per 120 min (P = 0.005) for insulin, 19.9 (SEM 2.44) v. 16 (SEM 1.92) nmol/l per 120 min (P = 0.042) for GIP, and 237.7 (SEM 16.32) v. 126.4 (SEM 23.48) kJ/300 min (P = 0.0029) for DIT respectively. Differences between GIP-AUC after HM and SM correlated significantly with differences between insulin-AUC after HM and SM (r2 0.62, P = 0.021). These findings demonstrate that homogenization of a meal results in a coordinated series of changes of physiological gastroentero-pancreatic functions and confirm that the physical state of the meal plays an important role in modulating endocrine and metabolic responses to food.

Cerebellar degeneration and hearing loss in a patient with idiopathic myenteric ganglionitis

A 35-year-old male with an 11-year history of intestinal pseudo-obstruction associated with an idiopathic inflammatory insult of the myenteric plexus and the presence of circulating anti-Hu antibodies developed a neurological syndrome characterized by bilateral hearing loss, deteriorating balance, an unsteady gait and difficulty in estimating distances. A similar neurological syndrome has previously been described in older patients among the paraneoplasic syndromes associated with small-cell lung carcinoma and the presence of circulating anti-Hu antibodies, but never in the rare cancer-free patients with anti-Hu-associated chronic idiopathic intestinal pseudo-obstruction. The patient underwent a steroid treatment. No further episodes of functional intestinal obstruction were observed and, after an initial improvement, the neurological symptoms stabilized, leaving a permanent reduction in hearing function and an unsteady gait. The case shows that an idiopathic inflammatory insult of the myenteric plexus may precede (and perhaps lead to) central nervous system impairment in patients with anti-Hu-associated chronic idiopathic intestinal pseudo-obstruction.

Elevated circulating somatostatin levels in acromegaly

GH increases hypothalamic somatostatin (SS) synthesis and secretion but it is unknown if chronic GH excess, as found in acromegaly, may influence circulating SS levels, that are mainly of enteropancreatic source and affect several gastrointestinal functions, including motility. Circulating SS occurs in several post-translational forms including somatostatin-14 (SS-14), somatostatin-28 (SS-28) and other small peptides. The aim of the present study was to characterize the fasting and postprandial pattern of plasma circulating somatostatin in normal subjects and patients with acromegaly. Fasting total SS and SS-28 levels were measured in 32 subjects, 16 acromegalic patients with a new diagnosis (A) (8 F, 8 M, median age 48) and 16 matched healthy volunteers (C) (8 F, 8 M, median age 45). SS was also determined after a standard solid-liquid meal (550 kCal) in 24 of the subjects (12 C and 12 A). Fasting SS and SS-28 were significantly higher in acromegalic patients as compared to healthy subjects. In the former, a positive correlation was found between IGF-I and SS levels (r=0.525 p<0.05). Furthermore, the ratio between SS (as pmol equivalent SS-14/l) and SS-28 was higher in the acromegalic patients than in the controls (3.4±2.1 vs 2.0±1.6, p<0.05). The postprandial SS peak, as well as the incremental area above baseline values, was similar in the patients and controls. In conclusion, fasting but not postprandial hypersomatostatinemia, mainly due to an increase in SS-14, characterizes acromegaly. Excess GH/IGF-I could be a causal factor in somatostatin hypersecretion. Conceivably this abnormality might play a role in some alterations of gastrointestinal function of acromegalic patients such as prolonged bowel transit.