Endocrine tumors of git

ENDOCRINE TUMORS OF GIT

Dr SIVARAJ SDEPT OF PHYSIOLOGY

ALL INDIA INSTITUTE OF MEDICAL SCIENCESNEW DELHI

• Derived from neuroendocrine system of the GI tract

• APUD cells (amine precursor uptake and decarboxylation) cells that make polypeptides and biogenic amines

• Divided intoI. Carcinoid tumorsII. Pancreatic endocrine tumors(PET)

WHO CLASSIFICATION

– Well differentiated NET (non-invasive, benign behaving or uncertain malignant potential)

– Well-differentiated NE carcinomas (low grade malignant and has invasion or muscularis propria or metastasis)

– Poorly differentiated endocrine carcinomas (high grade, malignant)

General characteristics

• Share general neuroendocrine cell markers• Pathologic similarities • Similarities of biologic behavior• Similarities/differences in molecular

abnormalities

Carcinoid tumors• Arise from enterochromaffin cells (Kulchitsky

cells) found in the crypts of Lieberkühn• Known as Argentaffin cells• Most common location Small Intestine(Ileum

14.9%)• Most common incidence of carcinoid

syndrome Pancreas(20%)• Most common incidence of metastasis

Pancreas(72%)

CLASSIFICATION• Carcinoid tumors

Foregut 25% Midgut 40-60% Hindgut

5HT/Serotonin low high low

Argentaffin negative positive negative

Carcinoid syndrome

Rarely & Atypical Frequently & Typical

rarely

Synthesis, secretion, and metabolism of 5-HT in patients Carcinoid syndromes

Secretory Products of Carcinoid Tumors

Sabiston Text book of surgery 18th edition

Carcinoid syndrome

• Symptoms/signs• Diarrhea• Flushing• Pain• Asthma/wheezing• Pellagra• Carcinoid heart disease

Diagnosis

• Measurement of urinary or plasma serotonin or its metabolites & 5-HIAA in the urine.

• Serum chromogranin A and NSE• CT useful in detecting metastases and the

extent tumor• Somatostatin receptor scintigraphy using 111In-

labeled pentetreotide

Sabiston Text book of surgery 18th edition

Treatment

• Carcinoid syndrome Histamine antagonist Somatostatin

analogues Oral bronchodilators IFN-α Hepatic artery

embolization

• Carcinoid tumorSurgical resection

Pancreatic Endocrine Tumors(PETs)

Zollinger-ellison syndromeInsulinomaGlucogonomaSomatostatinomaVIPomaGRFomaOther rare tumoursNon Functional PETs(NF PETs)

Gastrinoma/ZE syndrome

• Secretes gastrin• Symptoms/signs• Refractory and severe peptic ulcer• Chronic unexplained diarrhea• Associated with MEN I• Most common location Duodenum• 60–90% malignant

• Diagnosis Fasting gastrin level and basal gastric acid

output (BAO)• Treatment Proton pump inhibitors, H2receptor antagonist<15% hepatic mets without MEN I surgical

resection possible

Insulinoma

• Derived from Beta cells that secretes insulin• C/F due to hypoglycemia effect on CNS• distributed equally in pancreas• 10% multiple• 10% >2cm• 10% malignant• 10% asst with MEN I

• DiagnosisPlasma proinsulin/ C-peptide level in bloodRaised fasting insulin/glucose ratioMost reliable test 72 hr fasting test

• Treatment Mostly surgical Diazoxide Streptozotocin

Glucagonoma

• Dermatitis(migratory necrolytic erythema)• Glucose intolerance or diabetes• Weight loss• Mostly occur in tail• Diagnosis • Increased plasma glucagon level• Treatment with somatostatin analogues

Somatostatinoma

• Secretes excessive amounts of somatostatin• Cholelithiasis, DM, diarrhea, weight loss,

steatorrhea• Mostly occur in head• Treatment surgical for tumors without

metastasis

VIPoma/WDHA syndrome

• Secrete excessive amounts of VIP(vasoactive intestinal peptide)

• Watery Diarrhea, Hypokalemia, and Achlorhydria(WDHA)

• Mostly occur in Tail

• Diagnosis ↑Plasma VIP level , Presence of large-volume

diarrhea

• Treatment Replacing electrolytesSomatostatin analogues

GRF oma

• Suspect with abdominal tumours with acromegaly

• Treatment Somatostatin analogues Surgical treatment if metastasis not present

Other rare pancreatic endocrinetumor syndromes

• ACTHoma• PETs secreting PTHrP• PETs secreting calcitonin• PETs secreting renin• PETs secreting erythropoietin• PETs secreting LH

Non Functional PETs

• Symptoms entirely due to tumor per se• Present late• Occur primarily in the pancreatic head• secrete chromogranin,PP,HCG• Diagnosis by histological • Treatment surgical

Tumor Localization• CT• MRI• Transabdominal ultrasound• Endoscopic ultrasound – sensitivity/specificity

appx 80% for tumors in pancreas and duodenum and can allow for FNA

• Somatostatin receptor scintigraphy (SRS) based on presence of somatostatin receptors in 80-90% of NET

• PET scanning