GUT Hormones with an overview of GI NET

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Overview of Noncarcinoid GI NETs


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GUT Hormones with an overview of GI NET with a focus on Gastrinoma:

GUT Hormones with an overview of GI NET with a focus on Gastrinoma GUT Hormones with an overview of GI NET with a focus on Gastrinoma Venkata Lekharaju ( Pawan ) SPR GASTROENTEROLOGY 09/11/2012



NET (definition):

NET (definition) Neuroendocrine neoplasms , defined as epithelial neoplasms with predominant neuroendocrine differentiation, arise in most organs of the body

Synonyms to define NET:

Synonyms to define NET

PowerPoint Presentation:



GEP NET Neuroendocrine tumors comprise approximately 2% of all malignant tumors of the gastrointestinal system Incidence of all noncarcinoid NETs is approximately one half that of all carcinoids Noncarcinoid NETs have been reported to occur in 0.4–1.5/100,000 of the population



Basic biology of NET:

Basic biology of NET 14 endocrine cell types in the gut Produce at least 33 hormones and biogenic amines

Types of NET:

Types of NET The cell type-specific hormonal substance produced by the enteroendocrine cell defines the type of NETs originating from that cell Serotonin- carcinoid , Gastrin-gastrinoma , Vasoactive intestinal peptide- VIPoma , Insulin- insulinoma , Glucagon- glucagonoma


Genetics MEN type 1 Von- Hippel Lindau disease Neurofibromatosis type 1

Useful tips (if you can remember):

Useful tips (if you can remember) 57% of MEN type 1 has ZES 20% of ZES patients have MEN type 1 30% of all GFRomas are associated with MEN 1 4-5% of Insulinomas are associated with MEN 1 80% of MEN 1 develop PET No PETs are associated with MEN PETs occur in 12-17% of patients with VHL NF 1 is associated with duodenal somatostatinomas

Enteroendocrine tumor syndromes other than Carcinoid:

Enteroendocrine tumor syndromes other than Carcinoid


Insulinoma Syndrome: Insulinoma Hormone: Insulin, Proinsulin Clinical features: Hypoglycaemia, wt loss Site: >95% pancreas Malignant: >10% Treatment: Surgery, Diet, IV dextrose, chemotherapy, Diazoxide , SSTA


VIPOMA Syndrome: Verner -Morrison pancreatic cholera WDHA Hormone: VIP Clinical features: Secretory diarrhoea, hypokalemia , achlorhydria , metabolic acidosis, flushing, wt. loss Site: 90% pancreas Malignant: >50% Treatment: Surgery, IV fluids, chemotherapy, SSTA


Glucagonoma Syndrome: Glucagonoma syndrome Hormone: Glucagon Clinical features: Hyperglycaemia, necrolytic migratory erythema , DVT, depression Site: >90% pancreas Malignant: >50% Treatment: Surgery, Diet, Insulin, chemotherapy, SSTA


Somatostatinoma Syndrome: Somatostatinoma syndrome Hormone: Somatostatin Clinical features: Diabetes, gallstones, wtloss , steatorrhea Site: Pancreas Malignant: 70-80% Treatment: Surgery, Insulin, pancreatic enzymes

Extremely rare:

Extremely rare

Extremely rare:

Extremely rare Tumor Syndrome Hormone Features Site Malignant Treatment ACTHoma Ectopic Cushing’s syndorme ACTH HTN, DM Pancreas Lung >99% Surgery Chemo SSTA PTHrPoma Hyper parathyroidism PTHrP Hyper calcaemia Renal stones Pancreas >99% Surgery Chemo Neurotensinoma ? N eurotensin ? Pancreas Lung ? Surgery Chemo Calcitoninoma ? Calcitonin ? Pancreas Lung >80% Surgery Chemo GRFoma Acromegaly GHRF Acromegaly Pancreas Lung Thymus 30% Surgery SSTA

Nonspecific markers:

Nonspecific markers Chromogranin A Chromogranin B Pancreastatin Pancreatic polypeptide Neuron specific enolase Alpha and beta subunits of chorionic gonadotropin 5 HIAA (24hr Urine) (diet and meds)


Imaging Imaging is indicated at different stages in the patient’s care 1. Screening of at-risk populations 2. Primary lesion detection 3. Assessing extent of disease 4. Follow-up and assessing response to treatment.





Gold standard:

Gold standard SRS ( Somatostatin receptor scintigraphy ) 68 Ga DOTATOC PET Octreoscan = 111 In-DTPAOC SPECT Density of receptors (type 2 and 5) determines the result and not the tumor size Functionality of the tumor is not relevant Not useful if you are suspecting Insulinoma


Octreoscan Confirms the diagnosis and localizes a NET, Imaging metastases or staging, Monitoring progression or regression of tumors , Predicts response to cold somatostatin analog treatment (the more strongly positive SRS, the greater the likelihood of a favorable response to this treatment), and Predicts the likelihood of a favorable response to a therapeutic dose of radiolabeled somatostatin analog (peptide-receptor radionuclide therapy). A negative SRS in the presence of a progressing tumor could indicate more strongly the need for aggressive surgery and/or chemotherapy


Limitations Reduced sensitivity in smaller (sub-centimetre) lesions and in lesions exhibiting low receptor density; 2-day imaging protocol; and potential interference by co- adminstration of therapeutic somatostatin analogues


Histology Mitotic rate Microscopic necrosis

Grading system:

Grading system





New GP referral in a Gastro clinic:

New GP referral in a Gastro clinic A 65-year-old woman Abdominal discomfort has been present intermittently for the past year and is described as burning epigastric pain that improves with meals and increases with fasting. Upper endoscopy performed 6 months ago revealed a duodenal ulcer and duodenitis . Antral biopsy specimens were negative for Helicobacter pylori . Treatment was initiated with a proton pump inhibitor (PPI) but her symptoms persisted. PPI= Omeprazole 20mg BD

Case continues:

Case continues Past medical history is notable for hypertension and coronary artery disease. Medications include a PPI, thiazide diuretic, β-blocker, angiotensin -converting enzyme inhibitor, low-dose aspirin, and a statin . She denies using over-the-counter medications.

Case continues:

Case continues Physical examination shows normal vital signs, and mild tenderness to palpation of the epigastrium . Hemoglobin level is 13 g/ dL with a normal white blood cell and platelet count. Serum creatinine , alkaline phosphatase , and aspartate aminotransferase levels are normal.

What will you do?:

What will you do? Repeat endoscopy? A repeat endoscopy revealed duodenal erosions with healing of the previously observed duodenal ulcer. Repeat antral biopsy specimens were negative for H pylori and duodenal biopsy procedures performed during the second endoscopy revealed a slight increase in neutrophils without evidence of neoplasm or infection.

Clever SPR:

Clever SPR Checks fasting Gastrin level Fasting gastrin is 310ng/L (SI units) Normal is <100ng/L

What should be the approach to this patient with documented peptic ulcer disease and elevated fasting gastrin level?:

What should be the approach to this patient with documented peptic ulcer disease and elevated fasting gastrin level?

Peptic ulcer disease:

Peptic ulcer disease Protective factors Aggressive factors Mucous Mucosal blood flow Growth factors Prostaglandins Acid Pepsin H.pylori NSAIDS What is refractory ulcer?

Causes of refractory ulcer:

Causes of refractory ulcer Ischaemia , Lymphoma, Crohn’s disease, Amyloidosis , Sarcoidosis , Systemic mastocytosis , Drugs/toxins ( bisphosphonates , potassium chloride, mycophenolate mofetil , and clopidogrel ), Eosinophilic gastroenteritis Infection (cytomegalovirus, herpes simplex virus, tuberculosis, and syphilis)

When to suspect Gastrinoma:

When to suspect Gastrinoma Ulcers in unusual locations (second part of the duodenum and beyond), Ulcers refractory to standard medical therapy, Ulcer recurrence after acid-reducing surgery, Ulcers presenting with frank complications (bleeding, obstruction, and perforation)


Hypergastrinemia Gastric hypochlorhydria or achlorhydria ( eg , pernicious anemia ); Retained gastric antrum after gastric surgery; H pylori infection; Gastric outlet obstruction; Renal insufficiency; Small-bowel obstruction; and Conditions such as rheumatoid arthritis, vitiligo , diabetes mellitus, and pheochromocytoma


Hypergastrinemia PPI H2 receptor blockers

Zollinger Ellison Syndrome:

Zollinger Ellison Syndrome Peptic ulcer Severe ulcerative oesophagitis Diarrhoea


Epidemiology Accurate incidence not known Very rare 0.1 to 1% of patients with peptic ulcer disease M>F Age group 30-50 years Diagnosis usually delayed (4-6 years) More than 50% have liver mets at the time of diagnosis


Site 70% occur in the duodenum Less often malignant Tend to be small May be multiple


Types Sporadic Familial Common Solitary More malignant More common site is pancreas Rare Multiple Smaller

MEN type 1:

MEN type 1 Autosomal -dominant disorder that involves primarily 3 organ sites Parathyroid glands (80%–90%), Pancreas (40%–80%), and Pituitary gland (30%–60%). Obtaining a thorough family history is important when considering multiple endocrine neoplasia type I.

Clinical predictors of poor survival:

Clinical predictors of poor survival Liver mets Diffuse extent Bone mets Size >3cm Cushings syndrome Female sex Absence of MEN 1 Markedly raised serum gastrin

Diagnostic tests:

Diagnostic tests Fasting hypergastrinemia Basal acid output (BAO) is greater than 10 mEq /h. Secretin stimulation test


Treatment Role of surgery is controversial More useful in MEN 1 association Usually is Whipples PPI SST Analogues 5FU based regimens

GUT Hormones:

GUT Hormones

PowerPoint Presentation:

Hormone/peptide neurocrine endocrine paracrine VIP + Substance P + Neuropeptide + Somotostatin + + + Cholecystokinin + + Gastrin + Secretin + GIP + Motilin + + Neurotensin ? + + Guanylin + +

Summation of GUT hormones:

Summation of GUT hormones

PowerPoint Presentation:

Hormone Source Target Action Cholecystokinin I cell in duo, jeju, neurons in ileum, colon Pancreas gallbladder ↑ enz secretion ↑ contraction GIP K cell in duo, jeuju pancreas ↓ fluid absorp ↑ insulin release Gastrin G cell in antrum, duo Parietal cell ↑ aci d secretion ↑ motility GRP Vagus nerve G cell Gastrin r elease

PowerPoint Presentation:

Hormone Source Target Action Glucagon Alpha cell in pancreatic islet liver ↑ glycogenolysis ↑ gluconeogenesis Guanylin Ileum, colon Small and large intestine ↑ fluid secretion Motilin EC cell, Mo cell in upper GI tract Eso sphincter Stomach, duo Smooth muscle contraction Neurote nsin Neurons, ECC in ileum Intestinal smooth muscle ↓ GI motility ↑ blood flow

PowerPoint Presentation:

Hormone Source Target Action Peptide YY L cell in ileum, colon Stomach Pancrease ↓ vagal mediated acid secretion ↓ enz and fluid secretion Secretin S cell in small intestine Pancrease Stomach ↑ HCO3 and fluid secretion by pancreatic ducts ↓ gastric a secretion Somatostatin D cell in stomach , duodenum, pancreatic islet Stomach Intestine Pancrease Liver ↓ gastrin release ↑fluid absorption ↑ smm contraction ↓ endo /exocrine secretion ↓ bile flow

PowerPoint Presentation:

Hormone Source Target Action Substance P Enteric neurons Intestine Pancrease ↑ GI motility ↓ HCO3 secretion VIP ENS neurons Small intestine Pancrease smm contraction ↑SB secretion ↑pancreatic secretion

PowerPoint Presentation:


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