Pathophysiological study of diarrhoea in a patient with medullary thyroid carcinoma. Evidence against a secretory mechanism and for the role of shortened colonic transit time.

Abstract

SUMMARY Intubation techniques and scintigraphic studies were used to determine the origin and mechanism of diarrhoea in a patient with medullary thyroid carcinoma, high plasma immunoreactive calcitonin and normal circulating serotonin, substance P and prostaglandins E2 and F2,l.Normal function of the small intestine was found for the following: (a) absorption tests; (b) water and electrolyte absorption in the proximal jejunum; (c) 24 hour flow rate and composition of fluid entering the colon and (d) gastric emptying rate and small intestinal progression of a normal meal. By contrast, colonic function was markedly impaired in three ways: (a) water absorption was decreased by half; (b) as the main excreted solutes were organic acids, a large electrolyte gap was recorded in faecal water, and (c) colonic transit time of the meal marker was very short, and was in agreement with the rapid transit of ingested radioopaque markers. These data strongly suggest that decreased absorption in the colon secondary to a motor disturbance is the main mechanism of diarrhoea in this case of medullary thyroid carcinoma, while calcitonin induced small intestinal fluid secretion suggested earlier is either non-existent, or only of minor importance. whether or not diarrhoea is present, and its plasma concentration does not seem to correlate with intestinal dysfunction.4We report here a pathophysiological study of the increased faecal fluid losses in a case of MTC with diarrhoea and hypercalcitoninaemia. The results do not support the presence of a secretory mechanism, but strongly suggest that diarrhoea was the result of dysfunction of the colon caused by a marked shortening of the transit time of the intraluminal contents. Case historyA 41 year old man was admitted to hospital for chronic diarrhoea which had lasted for eight years. He passed six to 15 watery stools per day; motions were urgent and mainly postcibal, and the faeces 537 on 11 May 2018 by guest. Protected by copyright.

Phosphospecific Site Tyrosine Phosphorylation of p125FAK and Proline-rich Kinase 2 Is Differentially Regulated by Cholecystokinin Receptor Type A Activation in Pancreatic Acini

“…Specifically, activation of various G protein-coupled receptors results in mitogen-activated protein kinase activation that is PYK2-dependent but FAK-independent (5, 58, 59). Activation of both kinases has different effects on the regulation of the cell cycle (40,60), the regulation of apoptosis (61), the activation of Jun kinase (40,62), or the differential phosphorylation of substrates like p130 Cas (63), PAP (64), or Nirs (65). Our results demonstrating that CCK-stimulated phosphorylation of the homologous sites of FAK and PYK2 differs in magnitude and kinetics, supporting the conclusion that the differential activation of these two closely related kinases in pancreatic acini by CCK, may have an important role in mediating the ability of CCK to activate different cellular signaling cascades and have different cellular effects.…”

Thyroid disorders and gastrointestinal and liver dysfunction: A state of the art review

“…There was, however, marked reduction in the transit time of colonic contents [58]. Prostaglandins E2 and F2α, serotonin, and substance P are raised in patients with medullary thyroid cancer [59,60] and have been postulated as being involved in the pathogenesis of the cancer-associated diarrhoea [58]. Currently, it is thought that the cause of the diarrhoea may vary from one individual to another; prostaglandins, serotonin, and calcitonin do remain the likely culprits though [61].…”

“…It is thought to be hypersecretory and/or due to gastrointestinal hypermotility [57]. It was studied using scintigraphic investigations; the overall handling of water and ions in the small bowel was normal with normal gastric emptying, which makes calcitonin an unlikely culprit for the diarrhoea, albeit calcitonin is known to stimulate small intestinal mucosal secretion [58]. There was, however, marked reduction in the transit time of colonic contents [58].…”

“…It was studied using scintigraphic investigations; the overall handling of water and ions in the small bowel was normal with normal gastric emptying, which makes calcitonin an unlikely culprit for the diarrhoea, albeit calcitonin is known to stimulate small intestinal mucosal secretion [58]. There was, however, marked reduction in the transit time of colonic contents [58]. Prostaglandins E2 and F2α, serotonin, and substance P are raised in patients with medullary thyroid cancer [59,60] and have been postulated as being involved in the pathogenesis of the cancer-associated diarrhoea [58].…”

2012 European Thyroid Association Guidelines for Metastatic Medullary Thyroid Cancer

“…Diarrhea [72,73], ectopic corticotropin-releasing hormone and ectopic adrenocorticotropic hormone production that can result in Cushing syndrome [74] are the main hormonally mediated complications of MTC, most frequently in the setting of advanced disease and usually in patients with hepatic metastases. …”