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20180809 noon conference
- 2. © 2016 Virginia Mason Medical Center 2 Multiple Choice Question #1 What laboratory result is most consistent with a secretory cause of chronic diarrhea? 1. Positive stool Sudan stain 2. Anion gap metabolic acidosis 3. Positive stool C. diff antigen 4. Low stool osmotic gap 5. Abnormal cells found in an ova & parasite screen
- 3. © 2016 Virginia Mason Medical Center 3 Multiple Choice Question #1 What laboratory result is most consistent with a secretory cause of chronic diarrhea? 4. Low stool osmotic gap • Chronic diarrhea can be classified as inflammatory, fatty, or watery, with watery diarrhea being further subdivided into osmotic and secretory. • Secretory diarrhea occurs when luminal cells secrete fluid into the GI lumen. This fluid is often rich in sodium and potassium, causing a low stool osmotic gap • Stool Osmotic Gap = 290 – 2 * (Stool Na + Stool K)
- 4. © 2016 Virginia Mason Medical Center 4 Key results that led to the diagnosis… • Urinary 5-HIAA: 22.7 mg/24h (normal < 6 mg/24h) • Serum Chromogranin-A: 112 ng/mL (normal < 93 ng/mL) • CT Abdomen/Pelvis: 2.3 cm mass in distal ileum with hyper-vascular mass in liver
- 5. © 2016 Virginia Mason Medical Center 5 Key results that led to the diagnosis… • Urinary 5-HIAA: 22.7 mg/24h (normal < 6 mg/24h) • Serum Chromogranin-A: 112 ng/mL (normal < 93 ng/mL) • CT Abdomen/Pelvis: 2.3 cm mass in distal ileum with hyper-vascular mass in liver • PET Scan: Two adjacent foci of increased uptake in distal ileum and subtle increased uptake in liver
- 6. © 2016 Virginia Mason Medical Center 6 Key results that led to the diagnosis… • Urinary 5-HIAA: 22.7 mg/24h (normal < 6 mg/24h) • Serum Chromogranin-A: 112 ng/mL (normal < 93 ng/mL) • CT Abdomen/Pelvis: 2.3 cm mass in distal ileum with hyper-vascular mass in liver • PET Scan: Two adjacent foci of increased uptake in distal ileum and subtle increased uptake in liver Our patient was diagnosed with a small intestinal carcinoid tumor, metastatic to the liver, causing carcinoid syndrome
- 7. © 2016 Virginia Mason Medical Center 7 Objectives Carcinoid Syndrome • Discuss clinical presentation • Review etiology • Highlight diagnostic tests • Discuss treatment • Review illness script
- 8. © 2016 Virginia Mason Medical Center 8 Carcinoid Syndrome: Presentation • Discuss clinical presentation • Review etiology • Highlight diagnostic tests • Discuss treatment • Review illness script From: www.carcinoid.com/pdfs/an_overview_of_carcinoid_syndrome.pdf
- 9. © 2016 Virginia Mason Medical Center 9 Carcinoid Syndrome: Presentation • Common presenting symptoms are often vague, leading to delays in diagnosis • Carcinoid syndrome occurs in ~8% of patients with carcinoid tumors • Midgut carcinoids account for 80% of cases • 91% of the time, symptoms develop after metastasis to liver
- 10. © 2016 Virginia Mason Medical Center 10 Carcinoid Syndrome: Etiology Intestinal Mucosa Extracellular The enterochromaffin cell Afferent neuron Intestinalepithelialcell Enterochromaffin Cell Secretory Granules Filled with Chromogranin Tryptophan Serotonin 5-HT 5-HT 5-HT 5-HT 5-HT 5-HT 5-HT 5-HT GI Lumen 5-HT Receptor Motility, Secretion SST Receptor Vasodilation, Fibroblast activationBroken down to 5-HIAA
- 11. © 2016 Virginia Mason Medical Center 11 Multiple Choice Question #2 What is a common cause of artificially elevated 5-HIAA levels? 1. Eating bananas prior to testing 2. Medications that activate CYP3A4 enzymes 3. Chronic Kidney Disease 4. Administration of heparin 5. Assay cross-reactivity with urine nitrites
- 12. © 2016 Virginia Mason Medical Center 12 Multiple Choice Question #2 What is a common cause of artificially elevated 5-HIAA levels? 1. Eating bananas prior to testing • Serotonin-rich foods like bananas, pineapples, pecans, and avocados, and certain medications like guaifenesin, salicylates, and SSRIs can cause false elevations in urinary 5-HIAA • A typical 100g banana contains 1500ug of serotonin. Adding 2000ug (2mg) of serotonin to the body increases 24- hour urinary 5-HIAA by about 1mg. Thus, to get a 5-HIAA level of 22.7 like our patient, a person would have to ingest approximately 34 bananas in the day prior to examination!
- 13. © 2016 Virginia Mason Medical Center 13 Carcinoid Syndrome: Diagnosis • Biomarker testing • Urine 24-hour 5-HIAA • Serum Chromogranin A • Imaging • Abdominal CT • PET Scan
- 14. © 2016 Virginia Mason Medical Center 14 Carcinoid Syndrome: Treatment • Non-metastatic disease: Local surgical resection including mesentery + small bowel examination • Metastatic disease: Consider local resection for symptomatic control + liver metastectomy or ablation • Control symptoms with conservative management • Add somatostatin analogues to further control symptoms and slow tumor progression • Octreotide 150 mg SQ TID • Octreotide depot Qmonthly • Lantreotide depot Qmonthly
- 15. © 2016 Virginia Mason Medical Center 15 Carcinoid Syndrome: Prognosis Even patients with metastatic carcinoid tumors have a 5-year overall survival of 60-80%
- 16. © 2016 Virginia Mason Medical Center 16 Illness Scripts Carcinoid Syndrome Irritable Bowel Syndrome Pathophysiology Elevated serotonin secretion Functional disorder of GI tract Epidemiology Rare: 8 per million Age of onset >50 (avg 61) M > F Common: 10-15% prevalence Age of onset < 35 F > M Time course subacute/chronic subacute/chronic Clinical presentation Diarrhea, nocturnal diarrhea, abdominal cramping, flushing, telangiectasias, wheezing, valvular disease Diarrhea, NO NOCTURNAL DIARRHEA, constipation, abdominal cramping Diagnostics Labs: elevated serum CgA, elevated urinary 5-HIAA Imaging: Small intestinal mass, PET-avid. Hyper-vascular liver metastasis Tissue Biopsy: Increased, neoplastic, well- differentiated neuroendocrine cells Rome IV Criteria: Recurrent abdominal pain at least 1 day per week over at least 3 months associated with 2 or more of the following: - Pain related to defecation - Associated with change in stool frequency - Associated with change in stool form Therapeutics Local excision, somatostatin analogues Reassurance, dietary changes, symptomatic management, antidepressants
Editor's Notes
- Title your presentation “Noon Conference” Prevents inadvertently giving away the case.
- Characteristic presenting symptoms: Flushing, typically a “dry” flush that patients may characterize as feeling “hot”. Often comes on suddenly and lasts for a few minutes. Can be precipitated by certain foods, alcohol, exercise, Flush is often a deep red or violaceous color. Caused by excess systemic serotonin secreted from the carcinoid tumor. Diarrhea is often watery, and typically less than 1 liter per day Abdominal discomfort from local inflammation, partial small bowel obstructions, and localized ischemia from masses most commonly in the small intestine Right sided valvular heart lesions are also due to the fibrotic effects of systemic serotonin and most commonly causes tricuspid regurgitation, followed by tricuspid stenosis and pulmonary regurgitation. Patients with valvular disease often go on to develop congestive heart failure.
- Abdominal pain from local inflammation, partial small bowel obstructions, and localized ischemia Diarrhea is often watery, normally less than 1L per day
- Carcinoid syndrome arises from carcinoid tumors Carcinoid tumors are, by definition well-differentiated cancers of neuroendocrine cells throughout the body Neuroendocrine cells in most cases receive neuronal input and secrete hormones into the body. They are a diverse group of different cells and include things like adrenal medulla cells, pancreatic islet cells, gastrin secreting cells in the stomach, pulmonary cells that regulate pulmonary blood flow and bronchomotor tone, baroreceptor cells in the aorta, and enterochromaffin cells distributed widely throughout the GI tract Enterochromaffin cells are the most common neuroendocrine cells in the GI tract Main function is to take up tryptophan (typically less than 1% of total body tryptophan is utilized in this pathway), convert it into serotonin, and secrete it into the GI tract, which in turn helps to increase GI tract motility, coordinate peristalsis, and control the fluid levels inside the GI tract Somatostatin, a naturally occurring GI hormone, and its analogues like octreotide and lantreotide bind somatostatin receptors on neuroendocrine cells and inhibit their action. Additionally, with enough somatostatin signaling, neuroendocrine cells can even die. You can imagine that a significant increase in the number and function of enterochromaffin cells, which is what is happening during intestinal carcinoids, can take up a lot of the body’s tryptophan and produce a lot of serotonin. This GI serotonin is typically inactivated by hepatocytes in the liver, but when the disease becomes metastatic to the liver, it can expose the body to significant amounts of serotonin, causing the flushing, diarrhea, and valvular disease associated the syndrome.
- When a patient is suspected to have carcinoid syndrome, physicians can further work up the disease with biomarker and imaging tests Biomarker tests look for secretory products of carcinoid tumors, 5-Hydroxyindoleacetic acid – Sensitivity 90%, Specificity 90% Chromogranin A, also secreted by other neuroendocrine cells and elevated by PPIs so less useful. Sensitivity 90%, but specificity <50% CT scans may have difficulty identifying carcinoid tumors in the intestines as they are often small and multifocal, and hypervascular liver lesions typically appear isodense to surrounding liver in tests without contrast. Thus there is limited utility in this test PET Scan is better as these tumors and metastases tend to be highly metabolically active, and newer octreotate-based PET tracers are now in the clinic, further improving the efficiency of these tests
- Conservative management includes Flushing: avoiding provoking foods and medicines Diarrhea: loperamide Valvular heart disease: octreotide and serial TTEs
- Conservative management includes Flushing: avoiding provoking foods and medicines Diarrhea: loperamide Valvular heart disease: octreotide and serial TTEs