Clinicopathological Conference CPC

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Clinicopathological Conference CPC 6

• Todd T. Brown, MD, PhD
• Division of Endocrinology and Metabolism

45 y/o male with intermittent abdominal pain,
nausea, and diarrhea
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Questions

• Prior to surgery, what additional tests would
  help determine the cause of the patients
  symptoms?
• What are the most likely causes of the patients
  symptoms?
• What neoplasms can produce diarrhea as a symptom?
  By what mechanism(s) do they cause diarrhea?

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Salient Features

• 45 year old, male
• Chronic, episodic abdominal pain, diarrhea
• Diarrhea watery and profuse
• Weight loss
• 1.3 cm mass in head of pancreas
• (Symptoms resolved after surgical resection)

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abdominal pain, nausea, diarrhea
Diagnosis
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abdominal pain, nausea, diarrhea
Chronic, Intermittent
Diagnosis
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Chronic Diarrhea

• Fatty
• Inflammatory (RBCs/WBCs)
• Watery

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abdominal pain, nausea, diarrhea
Chronic, Intermittent
Watery
Diagnosis
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Work-up of Secretory Diarrhea

• r/o infection (stool culture, ova parasites,
  giardia antigen in stool)
• Evaluate for structural disease
• Endoscopy with biopsy
• Imaging

AGA Guidelines, 1999
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abdominal pain, nausea, diarrhea
Chronic, Intermittent
Watery
Secretory Diarrhea with Pancreatic Mass
Diagnosis
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Functional Neuroendocrine Tumors of the Pancreas
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Recommended Work-up

• Calcitonin
• Gastrin
• VIP
• Urinary 5-HIAA (serotonin metabolite)
• Somatostatin

• Other hormonal work-up for secretory diarrhea
• TSH
• ACTH stimulation test

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Glucagonoma

• Presentation 4Ds
• Diabetes
• Dermatitis
• Deep Vein Thrombosis
• Depression
• Dermatitis
• Necrolytic Migratory Erythema
• Resolves with amino acid supplementation
• Large at Presentation

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Carcinoid

• Arise anywhere in the GI tract (75-80 in small
  bowel, rare in pancreas)
• Many secretory products (histamine, serotonin
  most common)
• Flushing- histamine
• Diarrhea- serotonin
• Stimulation of intestinal secretion and motility

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Somatostatinoma

• Inhibits secretion of glucagon, growth hormone,
  insulin, gastrin
• Inhibits CCK-mediated secretion of pancreatic
  enzymes
• Clinical Syndrome Diabetes Mellitus,
  Cholelithiasis, Diarrhea
• Steatorrhea and resulting diarrhea from decreased
  secretion of pancreatic lipase

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Calcitonin

• Produced by C-cells in thyroid
• Elevations in calcitonin seen most often in
  medullary thyroid cancer
• Ectopic tumors can also produce calcitonin
• High calcitonin cause secretory diarrhea and
  flushing

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Gastrinoma

• 60 in pancreas, 30 in duodenum
• Presents as PUD (pain, GI bleed)- 90
• Diarrhea also a prominent symptom
• Large volume of gastric acid
• Acid damages gut mucosa
• Pancreatic enzymes inactive at low pH

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VIP-Secreting Tumors

• 90 in pancreas
• 70 have metastatic disease at presentation
• Classic Presentation watery diarrhea,
  hypokalemia, acidosis (WDHA syndrome)
• Other names pancreatic cholera syndrome,
  endocrine cholera, Verner-Morrison syndrome (1958)

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Vasointestinal Polypeptide

• 28-amino acid polypeptide
• Close structural homology with secretin
• Acts as a neurotransmitter
• Stimulates enteric smooth muscle and
  intestinal/pancreatic secretion, inhibits gastric
  acid secretion
• G-protein coupled receptors

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Mechanism of VIP-Associated Diarrhea
Effect of Cholera Toxin on Enterocytes
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Other Systemic Effects of VIP

• Decreased gastric acid secretion ?
  hypochlorhydria
• Bone resorption ? Hypercalcemia
• Glycogenolysis ? Hyperglycemia
• Vasodilation ? Flushing

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Hormonal Co-secretion in VIPoma

• Pancreatic Polypeptide
• Calcitonin
• Gastrin
• Neurotensin
• Gastric Inhibitory Peptide
• Serotonin
• Glucagon
• Insulin
• Somatostatin
• Growth Hormone Releasing Hormone

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MEN I and Neuroendocrine Tumors

• Autosomal dominant disease
• Parathyroid, Pituitary, Pancreas (3 Ps)
• Duodeno-pancreatic tumors
• Gastrin (Zollinger-Ellison Syndrome)(50-70)
• Insulin (20-40)
• Glucagonoma (1-2)
• VIPoma (lt1)
• Somatostatinoma (lt1)
• Family History, Serum Calcium, Prolactin
  important

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abdominal pain, nausea, diarrhea
Secretory Diarrhea with Pancreatic Mass
Pertinent Negatives No infectious causes No
anemia No PUD, nl EGD No flushing K 3.8, Ca
9.6
Additional Features Weight loss Diabetes
Mellitus Family History of Narcissism
Diagnosis
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abdominal pain, nausea, diarrhea
Secretory Diarrhea with Pancreatic Mass
VIP-producing Neuroendocrine Tumor of the Pancreas