Title: Clinicopathological Conference CPC
1Clinicopathological Conference CPC 6
- Todd T. Brown, MD, PhD
- Division of Endocrinology and Metabolism
45 y/o male with intermittent abdominal pain,
nausea, and diarrhea
2Questions
- 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?
3Salient 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)
4abdominal pain, nausea, diarrhea
Diagnosis
5abdominal pain, nausea, diarrhea
Chronic, Intermittent
Diagnosis
6Chronic Diarrhea
- Fatty
- Inflammatory (RBCs/WBCs)
- Watery
7abdominal pain, nausea, diarrhea
Chronic, Intermittent
Watery
Diagnosis
8Work-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
9abdominal pain, nausea, diarrhea
Chronic, Intermittent
Watery
Secretory Diarrhea with Pancreatic Mass
Diagnosis
10Functional Neuroendocrine Tumors of the Pancreas
11Recommended Work-up
- Calcitonin
- Gastrin
- VIP
- Urinary 5-HIAA (serotonin metabolite)
- Somatostatin
- Other hormonal work-up for secretory diarrhea
- TSH
- ACTH stimulation test
12Glucagonoma
- Presentation 4Ds
- Diabetes
- Dermatitis
- Deep Vein Thrombosis
- Depression
- Dermatitis
- Necrolytic Migratory Erythema
- Resolves with amino acid supplementation
- Large at Presentation
13Carcinoid
- 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
14Somatostatinoma
- 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
15Calcitonin
- 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
16Gastrinoma
- 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
17VIP-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)
18Vasointestinal 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
19Mechanism of VIP-Associated Diarrhea
Effect of Cholera Toxin on Enterocytes
20Other Systemic Effects of VIP
- Decreased gastric acid secretion ?
hypochlorhydria - Bone resorption ? Hypercalcemia
- Glycogenolysis ? Hyperglycemia
- Vasodilation ? Flushing
21Hormonal Co-secretion in VIPoma
- Pancreatic Polypeptide
- Calcitonin
- Gastrin
- Neurotensin
- Gastric Inhibitory Peptide
- Serotonin
- Glucagon
- Insulin
- Somatostatin
- Growth Hormone Releasing Hormone
22MEN 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
23abdominal 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
24abdominal pain, nausea, diarrhea
Secretory Diarrhea with Pancreatic Mass
VIP-producing Neuroendocrine Tumor of the Pancreas