Case Report: Severe Hypocalcemic Episodes Due to Autoimmune Enteropathy

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare monogenic disorder, associated with endocrine deficiencies and non-endocrine involvement. Gastrointestinal (GI) manifestations appear in approximately 25% of patients and are the presenting symptom in about 10% of them. Limited awareness among pediatricians of autoimmune enteropathy (AIE) caused by destruction of the gut endocrine cells in APECED patients delays diagnosis and appropriate therapy. We describe an 18-year-old female presenting at the age of 6.10 years with hypoparathyroidism, oral candidiasis and vitiligo. The clinical diagnosis of APECED was confirmed by sequencing the autoimmune regulator-encoding (AIRE) gene. Several characteristics of the disease—Hashimoto’s thyroiditis, Addison’s disease, diabetes mellitus type 1 and primary ovarian insufficiency—developed over the years. She had recurrent episodes of severe intractable hypocalcemia. Extensive GI investigations for possible malabsorption, including laboratory analyses, imaging and endoscopy with biopsies were unremarkable. Revision of the biopsies and chromogranin A (CgA) immunostaining demonstrated complete loss of enteroendocrine cells in the duodenum and small intestine, confirming the diagnosis of AIE. Management of hypocalcemia was challenging. Only intravenous calcitriol maintained calcium in the normal range. Between hypocalcemic episodes, the proband maintained normal calcium levels, suggesting a fluctuating disease course. Repeated intestinal biopsy revealed positive intestinal CgA immunostaining. The attribution of severe hypocalcemic episodes to AIE emphasizes the need for increased awareness of this unique presentation of APECED. The fluctuating disease course and repeated intestinal biopsy showing positive CgA immunostaining support a reversible effect of GI involvement. CgA immunostaining is indicated in patients with APECED for whom all other investigations have failed to reveal an explanation for the malabsorption.

Histomorphological and Cytochemical Characters of Endocrine Cells of the Gastrointestinal Mucosa of Duck (Anas platyrhynchos)

Background: It is known that balance diet is the key success for better production in poultry. The digestive physiology is regulated by the neurocrine and endocrine secretions. Growth, secretion, motility, cell signalling, vasoregulation, cell proliferation and differentiation of the epithelial cells of the alimentary canal are reported to be controlled by the peptides or amines released from the gut endocrine cells and enteric neurons. References particularly on systematic study of gastrointestinal endocrine cells in duck as regards to histomorphology and cytochemistry are gravely scanty. Hence the present investigation envisages authenticating the histomorphological characters and cytochemical behaviour of the gastrointestinal endocrine cells in duck.Methods: For this study the abdomen of six Khaki campbell ducks from either sex was cut open following euthanasia. Tissue pieces from different segments of gut were collected and processed routinely to get 7-8µ thick serial paraffin sections. The tissue sections were stained for evaluation of histomorphological and histochemical characters of the entero-endocrine cells.Result: A panel of seven cytochemical stains identified nine endocrine cell types in the digestive mucosa of Khaki Campbell duck i.e. basally granulated oval cell, densely granulated spindle shaped cell, densely granulated oval cell, diffusely granulated oval cell, pyramidal cell, densely granulated elongated cell, densely granulated pyriform cell, peripherally granulated spherical cell and non-argentaffin chromaffin oval cell. The cells occurred in single or in small clusters in the basal or middle or neck part of glandular epithelium or in the surface epithelium. All the endocrine cells were ‘close type’. Cytochemically they were four types i.e. argentaffin, argyrophil, chromaffin and APUD (Amine precursor uptake and decarboxylation) cells.

The role of diet in the pathophysiology and management of irritable bowel syndrome

Irritable bowel syndrome (IBS) is a chronic gastrointestinal (GI) disorder that reportedly affects 5% to 20% of the world population. The etiology of IBS is not completely understood, but diet appears to play an important role in its pathophysiology. Asian diets differ considerably from those in Western countries, which might explain differences in the prevalence, sex, and clinical presentation seen between patients with IBS in Asian and Western countries. Dietary regimes such as a low-fermentable oligo-, di-, monosaccharides, and polyols (FODMAP) diet and the modified National Institute for Health and Care Excellence (NICE) diet improve both symptoms and the quality of life in a considerable proportion of IBS patients. It has been speculated that diet is a prebiotic for the intestinal microbiota and favors the growth of certain bacteria. These bacteria ferment the dietary components, and the products of fermentation act upon intestinal stem cells to influence their differentiation into enteroendocrine cells. The resulting low density of enteroendocrine cells accompanied by low levels of certain hormones gives rise to intestinal dysmotility, visceral hypersensitivity, and abnormal secretion. This hypothesis is supported by the finding that changing to a low-FODMAP diet restores the density of GI cells to the levels in healthy subjects. These changes in gut endocrine cells caused by low-FODMAP diet are also accompanied by improvements in symptoms and the quality of life.

Revisiting the complexity of GLP-1 action-from sites of synthesis to receptor activation

Glucagon-like peptide-1 (GLP-1) is produced in gut endocrine cells and in the brain, and acts through hormonal and neural pathways to regulate islet function, satiety, and gut motility, supporting development of GLP-1 receptor (GLP-1R) agonists for the treatment of diabetes and obesity. Classic notions of GLP-1 acting as a meal-stimulated hormone from the distal gut are challenged by data supporting production of GLP-1 in the endocrine pancreas, and by the importance of brain-derived GLP-1 in the control of neural activity. Moreover, attribution of direct vs. indirect actions of GLP-1 is difficult, as many tissue and cellular targets of GLP-1 action do not exhibit robust or detectable GLP-1R expression. Furthermore, reliable detection of the GLP-1R is technically challenging, highly method-dependent, and subject to misinterpretation. Here we revisit the actions of GLP-1, scrutinizing key concepts supporting gut vs. extra-intestinal GLP-1 synthesis and secretion. We discuss new insights refining cellular localization of GLP-1R expression and integrate recent data to refine our understanding of how and where GLP-1 acts to control inflammation, cardiovascular function, islet hormone secretion, gastric emptying, appetite, and body weight. These findings update our knowledge of cell types and mechanisms linking endogenous vs. pharmacological GLP-1 action to activation of the canonical GLP-1R, and the control of metabolic activity in multiple organs.

Diet in Irritable Bowel Syndrome (IBS): Interaction with Gut Microbiota and Gut Hormones

Diet plays an important role not only in the pathophysiology of irritable bowel syndrome (IBS), but also as a tool that improves symptoms and quality of life. The effects of diet seem to be a result of an interaction with the gut bacteria and the gut endocrine cells. The density of gut endocrine cells is low in IBS patients, and it is believed that this abnormality is the direct cause of the symptoms seen in IBS patients. The low density of gut endocrine cells is probably caused by a low number of stem cells and low differentiation progeny toward endocrine cells. A low fermentable oligo-, di-, monosaccharide, and polyol (FODMAP) diet and fecal microbiota transplantation (FMT) restore the gut endocrine cells to the level of healthy subjects. It has been suggested that our diet acts as a prebiotic that favors the growth of a certain types of bacteria. Diet also acts as a substrate for gut bacteria fermentation, which results in several by-products. These by-products might act on the stem cells in such a way that the gut stem cells decrease, and consequently, endocrine cell numbers decrease. Changing to a low-FODMAP diet or changing the gut bacteria through FMT improves IBS symptoms and restores the density of endocrine cells.