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MSc Endocrinology > Endocrine Disorders Investigations > Flashcards

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
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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)
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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
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4
Q

What is Pancreatic Exocrine Function stimulated and inhibited by?

A

Stimulated by:

  • Secretin
  • CCK
  • VIP

Inhibited by:

  • Somatostatin
  • Pancreatic polypeptide
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5
Q

What is the Clinical Triad of Pancreatic Insufficiency?

A
  • Steatorrhoea
  • Diabetes mellitus
  • Pancreatic calcification
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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
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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
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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

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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)
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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.
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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
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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
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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
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14
Q

How is measurement of Pancreatic enzymes in blood?

A
  • Amylase
  • Lipase
  • Trypsinogen
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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
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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
Q

How does Coeliac disease present?

A

Wide spectrum of presentation:

  • Steatorrhoea
  • Abdominal pain
  • Bloating
  • Reduced absorption
  • Weight loss
  • Low B12 + anaemia
  • Osteoporosis
  • Association with other auto immunes diseases.
26
Q

What are investigatons for Coeliac disease?

A

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
Q

What is Disaccharide Deficiency?

A

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
Q

What are tests for Disaccharide deficiency?

A
  • Lactose challenge: measure glucose post load
  • Urine/faecal sugar chromatography
  • Hydrogen breath tests
  • Biopsy is definitive
29
Q

What is Inflammatory Bowel Disease?

A

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
Q

What are symptoms of Inflammatory Bowel Disease?

A
  • Abdominal pain,
  • Vomiting, diarrhoea,
  • Rectal bleeding, severe internal cramps/muscle spasms,
  • Weight loss.
31
Q

What is IBS and its symptoms?

A

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
Q

What are tests for Inflammatory Bowel Diseases?

A

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
Q

What are new markersof IBD on the horizon?

A

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
Q

What non-biochemical tests of Inflammatory Bowel Disease?

A
  • 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

MSc Endocrinology (16 decks)

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