Endocrine Disorders Investigations Flashcards
1
Q
What is the indications for invoking pancreatic and intestinal testing?
A
- Chronic Diarrhoea (>4 weeks): n.b lots of causes
- Suspected malabsorption
- Steatorrhoea
- Anaemia/bleeding/bruising
- Failure to thrive
- Abdominal discomfort/bloating/distension
- Suspicious findings on imaging (CT/MRI).
- Gauge severity of known pancreatic insufficiency
2
Q
What is the function of Pancreas?
A
Exocrine function (~80% of overall function)
- Acinar cells - secrete digestive enzymes
- Centroacinar/duct cells (ductal) - secrete fluid and electrolytes
Endocrine function. Islets of Langerhans producing:
- Insulin (b-cells = ~70% of the islet mass)
- Glucagon (a-cells)
- Pancreatic polypeptide (F-cells)
- Somatostatin (Delta cells)
3
Q
What are enzymes secreted by the Pancreas?
A
- Trypsin
- Chymotrypsin
- Carboxypeptidases A and B
- Elastase
- Amylase
- Lipase (+ colipase) -> converts Trigs to MAG and FFA’s. Colipase is a small protein co-factor different peptidases
4
Q
What is Pancreatic Exocrine Function stimulated and inhibited by?
A
Stimulated by:
- Secretin
- CCK
- VIP
Inhibited by:
- Somatostatin
- Pancreatic polypeptide
5
Q
What is the Clinical Triad of Pancreatic Insufficiency?
A
- Steatorrhoea
- Diabetes mellitus
- Pancreatic calcification
6
Q
How does Pancreatic Insufficiency develop?
A
Rare.
- Pancreas has large reserve capacity - malabsorption may not occur until >90% of the pancreas is destroyed (Uncommon in acute pancreatitis)
- Can result from Chronic pancreatitis due to infection, chronic alcohol excess, hyper-lipidaemia, Inherited causes e.g. Cystic Fibrosis / trypsin gene mutations
- Can lead to Pancreato/bilary cancer
7
Q
What are Pancreatic Function Testing types?
A
Invasive (Direct)
- More sensitive
- More specific
- Require intubation
- Expensive
- Radiation risk during placement of tube
- Require expertise
- Time consuming
Non invasive (Indirect)
- Less sensitive
- Less specific
- No intubation
- Relatively cheap
- Varying degrees of expertise required
8
Q
How is an Invasive Pancreatic Function test conducted?
A
- Stimulate pancreatic secretion using either: i.v hormones, ingestion of test meal, infusion of nutrients
- Collect and analyse duodenal secretions which requires duodenal and gastric tubes
Can add infusion of non-absorbable marker for calculation of enzyme outputs
9
Q
What is measured for each hormone in the Pnacreatic Function tests?
A
I.V secretin
- Volume of fluid
- [bicarbonate]
I.V CCK
- Amylase
- Trypsin
- Lipase
I.V secretin and CCK
- Volume
- Bicarbonate
- Amylase
- Trypsin
- Lipase
Lundh test meal (6% fat, 5% protein, 15% CHO in corn oil)
- Volume
- Tryptic activity (duodenal contents are aspirated at 15 min intervals for 2 hours)
10
Q
What is ERCP(Endoscopic retrograde cholangio-pancreatography)?
A
- A technique that combines the use of endoscopy and fluoroscopy to diagnose and treat certain problems of the biliary or pancreatic ductal systems
- Direct stimulation of pancreas with aspiration of pancreatic secretions
- Can also inject bile tract with dye to inspect the structure of the ducts
- Can often perform treatment (e.g. stone removal) at the same time.
- Being replaced by MRI scanning as less invasive and does not require sedation.
11
Q
What are types of Non-Invasive pancreatic fucntion tests?
A
- Measurement of unabsorbed food in stool
- Measurement of pancreatic enzymes: stool and blood
- Measurement of products of digestion (food or synthetic) which are hydrolysed by pancreatic enzymes, absorbed in the GI tract, and appear in the plasma, urine or breath
12
Q
How is measurement of Unabsorbed food in stool undertaken?
A
- Unpleasant for patients and staff, requires complete 3 day collection and requires regulated fat intake
- Poor sensitivity
Can be modified by:
- Addition of marker to identify beginning and end of test
- 2 stage test with pancreatic enzyme supplements
13
Q
Which Pancreatic enzymes in stool are measured?
A
Faecal elastase (= most popular of these two in U.K)
- Stable in faeces
- Measured by 2 site monoclonal ELISA
- Sensitivity/ specificity ~ 90%
Faecal chymotrypsin
- Chymotrypsin stable in stool
- Easy to measure - colorimetric assay.
- Maybe false positive in other causes of malabsorption
14
Q
How is measurement of Pancreatic enzymes in blood?
A
- Amylase
- Lipase
- Trypsinogen
15
Q
How is measurement of products of food digestion or products of synthetic compounds undertaken?
A
- NBT-PABA test (bentiromide test)
- Pancreolauryl test
- Breath tests
16
Q
What are some breath tests undertaken for the Pancreas?
A
Fat malabsorption
- 14 C triolein breath test
- 14 C cholesteryl octanoate breath test
- 13 C mixed triglyceride breath test →→ Measure 14/13CO2
CHO malabsorption
- 13 C starch breath test →→ Measure 14/13CO2
17
Q
What is Cystic Fibrosis?
A
- Autosomal recessive genetic disorder that affects most critically the lungs, and also the pancreas, liver, and intestine.
- It is characterized by abnormal transport of chloride and sodium across an epithelium (due to mutationa in CTFR gene), leading to thick, viscous secretions.
- Typically think of lung disease, but also affects pancreatic secretions: thickens pancreatic secretions, blocked ducts, reduced exocrine function and with malabsorption
- Sweat testing and CF genetic testing done for diagnosis
18
Q
What are types of Intestinal Function tests?
A
Haematological and biochemical tests
Tests for diarrhoea
- Faecal tests
- Tests for laxative abuse
- Endocrine causes of diarrhoea
- Bacterial/viral
Specific tests for malabsorption
- CHO absorption e.g. disaccharide deficiency
- Fat absorption
19
Q
What are the haemotological and biochemical tests?
A
Haematological and biochemical tests:
- FBC
- Vitamin B12 (? Pernicious anaemia) folate, iron
- Ca2+, PO4, Mg2+, ALP, albumin
Immunological tests:
- anti TTG antibodies
- Anti Intrinsic Factor Abs (? Pernicious anaemia)
- Microbiological – Infection screen
20
Q
What are Faecal tests for Diarrhoea in Intestinal functon testing?
A
Secretory vs. Osmotic diarrhoea
- Measure stool water osmolality and electrolytes
- Calculate osmotic gap (= stool osmo – 2x{stool Na + K})
- Normal gap = < 50
- High gap indicates osmotic diarrhoea due to
- (undigested/unabsorbed compounds)
- Low gap indicates secretory diarrhoea due to e.g.
- bacterial toxins/secretagogues e.g. VIP, gastrinoma, laxatives
Stool pH
Urine phenolphthalein / senna - Tests for laxative abuse
21
Q
What are some endocrine Tests for diarrhoea?
A
- Chromogranin A, 5-HIAA → Carcinoid Syndrome
- Gastrin (Zollinger Ellison syndrome)
- CCK, secretin, PP, GIP, VIP, motilin (Gut hormone profile on fasting plasma)
- Tumours secreting VIP can cause profuse watery diarrhoea -WDHA-(Werner-Morrison syndrome):Watery diarrhoea, Hypokalaemia, Achlorhydria (low/absent gastric acid secretion)
22
Q
What are considerations to take into account for endocrine tests for diarrhoea?
A
- GIT hormones are small AA peptides with very short half lives so, hormones are extremely labile and difficulty to measure.
- Requires fresh fasting sample to be collected on ice and processed immediately.
- Has to be endocrine/GIT consultant request
23
Q
What are some specific tests for malabsorption?
A
CHO absorption tests:
- Xylose absorption test (challenge test)
- Lactose tolerance test - for lactase deficiency
- H2 breath test for bacterial overgrowth
- Urine/faecal sugar chromatography
- D-Lactate (lactate of bacterial origin, not measured by most lab Lactate methods). Can cause metabolic acidosis (increased Anion Gap) of unclear origin.
Fat absorption tests
- Faecal fat / faecal globules on microscopy
- 14 C triolein breath test + others.
24
Q
What is Coeliac Disease?
A
- Lifelong autoimmune disease, affects individuals of all ages, affecting 1-100 – 1 in 200 US (most prevalent gut disease in Caucasians).
- Caused by autoimmune reaction to gliadins, a prolamin (gluten protein) found in wheat, barley and rye, having been modified the tissue enzyme tissue trans-glutaminase (TTG)
- Results in inflammatory damage to intestinal epithelium and loss of villi (villous atrophy).
25
How does Coeliac disease present?
Wide spectrum of presentation:
* Steatorrhoea
* Abdominal pain
* Bloating
* Reduced absorption
* Weight loss
* Low B12 + anaemia
* Osteoporosis
* Association with other auto immunes diseases.
26
What are investigatons for Coeliac disease?
**First line test:** Anti-TTG Abs (98% sens, 96% spec).
* These are IgA Abs, but some individuals are IgA deficient so must also check IgG anti - TTG Abs.
**2nd Line**
* anti-Endomysial Abs(can still be used to confirm ^TTGabs)
* anti Reticulin and anti Gliadin abs
**Biopsy is often required for full diagnosis to look for villous atrophy). Gluten free diet/gluten challenge before biopsy**
**Others:** H2 breath test, NBT-PABA and faecal elastase used to exclude other causes of symptoms.
DNA Test: HLA-DQ2/DQ8, used in children to avoid biopsy.Approx. \> 95% of CD patients are positive for DQ2 or DQ8, + carrying one of these alleles confers a 36-50% risk for CD.
27
What is Disaccharide Deficiency?
Deficiency of disaccharide sugar-digesting enzymes e.g. Lactase, sucrase-isomaltase, and trehlase.
* Lactase deficiency (most common): can be congenital or acquired (more common, as levels drop with age).
* When lactase levels too low get bloating and diarrhoea, after milk consumption.
28
What are tests for Disaccharide deficiency?
* Lactose challenge: measure glucose post load
* Urine/faecal sugar chromatography
* Hydrogen breath tests
* **Biopsy is definitive**
29
What is Inflammatory Bowel Disease?
Group of inflammatory conditions affect the GIT. Autoimmune disorders characterised by nature and location
* Crohn’s – can affect any part of GIT
* Ulcerative Colitis – mainly colon and rectum
Both disorders are lifelong conditions and can causes catastrophic damage to the GI tract in severe cases. Incurable but can be managed
30
What are symptoms of Inflammatory Bowel Disease?
* Abdominal pain,
* Vomiting, diarrhoea,
* Rectal bleeding, severe internal cramps/muscle spasms,
* Weight loss.
31
What is IBS and its symptoms?
Cause unknown, but believed to be infection and/or stress.
* Both syndromes characterised by: Chronic abdominal pain, discomfort, Bloating, Altered bowel habits.
* Causes discomfort for patients but unlike IBD, IBS is not associated with serious morbidity.
32
What are tests for Inflammatory Bowel Diseases?
Biochemical: Faecal Calprotectin
* Protein of S100 family found in neutrophils. Released during inflammation.
* Faecal levels is raised in IBD, but NOT IBS
* Used to help screen patients for IBS and avoid colonoscopy.
* Test is now being rapidly adopted by most larger UK labs.
* Sensitivity and Specificity of FCal for IBD = ~ 80%
Definitive diagnosis: Biopsy, and Capsule camera.
33
What are new markersof IBD on the horizon?
**M2-PK**
* Isoform of pyruvate kinase increased in colorectal carcinoma, and IDB
* Studies suggest M2-PK maybe a more sensitivity/specific marker for IBD than FCAL, but won't be adopted until we receive demand from clinicians.
**Faecal Alpha 1 anti trypsin.**
* Protease inhibitor present in many tissues protecting cells from action of proteolytic enzymes released during inflammation (clinical consequences A1AT deficiency covered in other lectures).
* A1AT can be detected in faeces during intestinal inflammation.
* At AH, increasingly used to investigate protein-losing enteropathy – a cause of protein loss and low proteins in patients.
34
What non-biochemical tests of Inflammatory Bowel Disease?
* ***Microbiology:*** Salmonella, Shigella, E coli, Campylobacter etc.
* ***Haematology:*** Schilling test for terminal ileal disease. (B12 uptake test)
* ***Histology:*** Duodenal/jejunal biopsies, colonoscopy for inflammatory bowel disease
* ***Imaging:*** US, MRI, CT, Ba studies, ERCP
* ***Endoscopy***
