Clinical Significance of Commonly Measured Laboratory Analytes

Transcription

1 Clinical Significance of Commonly Measured Laboratory Analytes i

2 Analyte Section Page 1-25-(OH 2 ) Vitamin D Immunoassay OH-Progesterone Immunoassay OH-Vitamin D Immunoassay 19 5-HIAA (5-Hydroxyindoleacetic acid) Clinical Chemistry 1 Acetaminophen Therapeutic Drugs 26 Acid Phosphatase Clinical Chemistry 1 ACE Clinical Chemistry 1 ACTH Immunoassay 11 Activated Partial Thromboplastin Time (aptt) Coagulation 30 Adiponectin Immunology 20 Adrenaline Clinical Chemistry 3 AFP Immunoassay / Immunology 11 / 20 Albumin Clinical Chemistry 1 Aldolase Clinical Chemistry 2 Aldosterone Immunoassay 12 Alkaline Phosphatase Clinical Chemistry 2 Alpha-1-Acid Glycoprotein Immunology 21 Alpha-1-Antitrypsin Immunology 20 Alpha-2-Macroglobulin Immunology 21 ALT Clinical Chemistry 2 Aluminium Clinical Chemistry 2 Amikacin Therapeutic Drugs 25 Amiodarone Therapeutic Drugs 25 Amitriptyline Therapeutic Drugs 26 Ammonia Clinical Chemistry 2 Amylase Clinical Chemistry 2 Androstenedione Immunoassay 12 Anti-EBNA Infectious Diseases 32 Anti-EBV VCA Infectious Diseases 32 Anti-HBc Infectious Diseases 32 Anti-TG Immunoassay 12 Anti-thrombin III Immunology / Coagulation 21 / 30 Anti-TPO Immunoassay 12 Apolipoprotein A-1 Immunology 21 Apolipoprotein B Immunology 21 Apolipoproteins A-II, C-II, C-III, E Immunology 21 ASO Immunology 21 Aspirin Therapeutic Drugs 26 AST Clinical Chemistry 2 Basophils Haematology 28 Beta-2-Microglobulin Immunoassay / Immunology 12 / 21 Beta-Hydroxybutyrate Clinical Chemistry 5 Bile Acids Clinical Chemistry 2 Bilirubin Clinical Chemistry 3 BNP Immunoassay 12 CA125 Immunoassay 12 CA15-3 Immunoassay 13 ii

3 CA19-9 Immunoassay 13 CA27.29 Immunoassay 13 CA72-4 Immunoassay 13 Cadmium Clinical Chemistry 3 Caeruloplasmin Immunology 22 Caffeine Therapeutic Drugs 26 Calcitonin Immunoassay 13 Calcium Clinical Chemistry 3 Carbamazepine Therapeutic Drugs 26 Catecholamines Clinical Chemistry 3 CEA Immunoassay 13 Chloramphenicol Therapeutic Drugs 25 Chloride Clinical Chemistry 5 Cholesterol Clinical Chemistry 4 Cholinesterase Clinical Chemistry 4 Chromium Clinical Chemistry 4 CK-MB Clinical Chemistry 5 CMV (Cytomegalovirus) Infectious Diseases 34 Cobalt Clinical Chemistry 4 Complement C3 Immunology 22 Complement C4 Immunology 22 Conjugated Bilirubin Clinical Chemistry 3 Copper Clinical Chemistry 4 Cortisol Immunoassay 13 C-Peptide Immunoassay 14 Creatine Kinase (CK) Clinical Chemistry 5 Creatinine Clinical Chemistry 5 CRP Immunology 22 Cyclosporine Therapeutic Drugs 26 Cyfra 21-1 Immunoassay 14 Cystatin C Immunology 22 D-3-Hydroxybutyrate Clinical Chemistry 5 D-dimer Immunoassay 14 Desipramine Therapeutic Drugs 26 DHEA-Sulphate Immunoassay 14 Digitoxin Therapeutic Drugs 25 Digoxin Therapeutic Drugs 25 Direct Bilirubin Clinical Chemistry 3 Dopamine Clinical Chemistry 3 Electrolytes Clinical Chemistry 5 Eosinophils Haematology 28 Epinephrine Clinical Chemistry 3 Epstein Barr Virus (EBV) Infectious Diseases 32 Erythrocytes Haematology 27 ESR (Erythrocyte Sedimentation Rate) Clinical Chemistry 5 Estradiol Immunoassay 16 Estriol, Unconjugated Immunoassay 16 Ethosuximide Therapeutic Drugs 26 iii

4 Everolimus Therapeutic Drugs 26 Factor II, V, VII, VIII, IX, X, XI, XII Coagulation 30 Ferritin Immunoassay / Immunology 14 / 22 Fibrinogen Coagulation 31 FK506 Therapeutic Drugs 26 Folate Immunoassay 14 Free T3 Immunoassay 18 Free T4 Immunoassay 18 Fructosamine Clinical Chemistry 6 FSH Immunoassay 15 Fugimycin Therapeutic Drugs 26 G6PD Clinical Chemistry 6 Gamma GT Clinical Chemistry 6 Gastrin Immunoassay 15 Gentamicin Therapeutic Drugs 25 GLDH Clinical Chemistry 6 Glucose Clinical Chemistry 6 Glutathione Peroxidase (GPx) Clinical Chemistry 6 Glutathione Reductase Clinical Chemistry 6 Granulocytes Haematology 28 Growth Hormone Immunoassay 15 Haematocrit Haematology 27 Haemoglobin Haematology 27 Haptoglobin Immunology 22 HbA1c Immunology 23 HBsAg Infectious Diseases 32 hcg Immunoassay 15 HDL Cholesterol Clinical Chemistry 4 Hepatitis B (HBV) Infectious Diseases 32 Hepatitis C (HCV) Infectious Diseases 32 H-FABP Immunology 23 HIV Infectious Diseases 32 HSV (Herpes Simplex Virus) Infectious Diseases 34 HTLV Infectious Diseases 33 Imipramine Therapeutic Drugs 26 Immunoglobulins (IgA, IgE, IgG, IgM) Immunology 23 Indirect Bilirubin Clinical Chemistry 3 Inhibin A Immunoassay 15 Insulin Immunoassay 15 Insulin Like Growth Factor (IGF-1) Immunoassay 16 International Normalised Ratio (INR) Coagulation 30 Iodine Clinical Chemistry 6 Iron Clinical Chemistry 7 Kappa Light Chain Immunology 23 Lactate Clinical Chemistry 7 Lambda Light Chain Immunology 23 LDH Clinical Chemistry 7 LDL Cholesterol Clinical Chemistry 4 iv

5 Lead Clinical Chemistry 7 Leukocytes Haematology 27 LH Immunoassay 16 Lidocaine Therapeutic Drugs 25 Lipase Clinical Chemistry 7 Lipoprotein (a) Immunology 23 Lithium Therapeutic Drugs 26 Lymphocytes Haematology 28 Magnesium Clinical Chemistry 7 Manganese Clinical Chemistry 8 Mean Cell Haemoglobin (MCH) Haematology 27 Mean Cell Haemoglobin Concentration (MCHC) Haematology 27 Mean Cell Volume (MCV) Haematology 27 Mean Platelet Volume (MPV) Haematology 28 Metanephrine Clinical Chemistry 3 Methotrexate Therapeutic Drugs 26 Microalbumin Immunology 24 Molybdenum Clinical Chemistry 8 Monocytes Haematology 28 Myoglobin Immunology 24 NAPA Therapeutic Drugs 25 NEFA Clinical Chemistry 8 Neutrophils Haematology 28 Nickel Clinical Chemistry 8 Nitrites Clinical Chemistry 8 Norepinephrine (Noradrenaline) Clinical Chemistry 3 Normetanephrine Clinical Chemistry 3 Nortriptyline Therapeutic Drugs 26 NSE Immunoassay 16 NT-proBNP Immunoassay 12 Oestradiol Immunoassay 16 Oestriol, Unconjugated Immunoassay 16 Orosomucoid Immunology 21 Osmolality Clinical Chemistry 8 Osteocalcin Immunoassay 16 Oxalate Clinical Chemistry 8 Packed Cell Volume Haematology 27 Pancreatic Amylase Clinical Chemistry 2 PAPP-A Immunoassay 16 Paracetamol Therapeutic Drugs 26 Phenobarbital Therapeutic Drugs 26 Phenytoin Therapeutic Drugs 26 Phosphate Clinical Chemistry 9 Plasminogen Coagulation 31 Platelets Haematology 28 Potassium Clinical Chemistry 5 Prealbumin Immunology 24 Primidone Therapeutic Drugs 26 v

6 Procainamide Therapeutic Drugs 25 Procalcitonin (PCT) Immunoassay 16 Progesterone Immunoassay 17 Prolactin Immunoassay 17 Prostatic Acid Phosphatase Clinical Chemistry 1 Protein C Coagulation 31 Protein S Coagulation 31 Protein (Total) Clinical Chemistry 9 Protein Electrophoresis Clinical Chemistry 9 Prothrombin Time (PT) Coagulation 30 PSA Immunoassay 17 PTH Immunoassay 17 Quinidine Therapeutic Drugs 25 Rapamycin Therapeutic Drugs 26 RBC Haematology 27 RBP (Retinol Binding Protein) Immunology 24 Red Blood Cell Distribution Width (RDW) Haematology 28 Renin Immunoassay 17 RF (Rheumatoid Factor) Immunology 24 RPR Infectious Diseases 33 Rubella Infectious Diseases 34 Salicylate Therapeutic Drugs 26 Selenium Clinical Chemistry 9 SHBG Immunoassay 18 Sirolimus Therapeutic Drugs 26 sldl Cholesterol Clinical Chemistry 4 Sodium Clinical Chemistry 5 Somatomedin C Immunoassay 16 Superoxide Dismutase Clinical Chemistry 9 Syphilis Infectious Diseases 33 T3 Immunoassay 18 T4 Immunoassay 18 Tacrolimus Therapeutic Drugs 26 Testosterone Immunoassay 18 Thallium Clinical Chemistry 10 Theophylline Therapeutic Drugs 26 Thrombin Time (TT) Coagulation 30 Thyroglobulin Immunoassay 18 TIBC Clinical Chemistry 7 Tobramycin Therapeutic Drugs 25 ToRCH Panel Infectious Diseases 34 Total Protein Clinical Chemistry 9 Toxoplasmosis Infectious Diseases 34 TPHA / TPPA Infectious Diseases 33 Transferrin Immunology 24 Transthyretin Immunology 24 Triglycerides Clinical Chemistry 10 Troponin Immunoassay 18 vi

7 TSH Immunoassay 19 TSH Receptor Antibody Immunoassay 19 T-Uptake Immunoassay 19 UIBC Clinical Chemistry 7 Unconjugated Bilirubin Clinical Chemistry 3 Unconjugated Oestriol (UE3) Immunoassay 16 Urea Clinical Chemistry 10 Uric Acid (Urate) Clinical Chemistry 10 Urobilinogen Clinical Chemistry 10 Valproic Acid Therapeutic Drugs 26 Vancomycin Therapeutic Drugs 25 VDRL Infectious Diseases 33 Vitamin B12 Immunoassay 19 VMA (Vanillymandelic Acid) Clinical Chemistry 3 WBC Haematology 28 WBC Differential Haematology 28 Zinc Clinical Chemistry 10 vii

8 Clinical Chemistry analytes Clinical Chemistry, or Clinical Biochemistry, tests are primarily run on serum / plasma and urine samples to assess e.g. tissue damage, liver function, kidney function and heart disease risk. Randox supplies a range of biochemistry analysers, along with the corresponding reagents, but can also supply many of the below chemistries for use on other manufacturers machines. The below key indicates whether these analytes are serum, whole blood or urine tests, and indicates where Randox can supply a reagent. Randox can supply either an internal control material or RIQAS programme (or in many instances, both IQC and RIQAS) for all of the below tests. Serum / plasma test Urine test Whole blood test Randox reagent available Randox IQC available RIQAS programme available 5-HIAA (5-Hydroxyindoleacetic acid) 5-HIAA is a metabolite of serotonin i.e. it is produced when serotonin is broken down. It is excreted from the body in the urine. Normally, only small amounts are found in the urine; large amounts can be present in patients with carcinoid tumours that secrete serotonin. This test may not be run in the routine biochemistry setting; it is more likely to be run in a Special Chemistry or Biogenic Amine lab. ACE (Angiotensin Converting Enzyme) ACE is most commonly measured to diagnose and monitor sarcoidosis, a condition that causes the development of granulomas (masses of inflammatory cells) in various organs, most commonly the lungs. ACE is typically elevated in these patients. The test can be used to distinguish sarcoidosis from other conditions that cause granuloma formation, such as TB or some fungal infections. Acid Phosphatase (ACP) and Prostatic Acid Phosphatase (PAP) Acid phosphatases are enzymes found in a number of tissues, most notably in the prostate gland. The test may be run to monitor treatment for prostate cancer, in which serum levels will be elevated. However, it has been largely superseded by the PSA test. Albumin Albumin is the major constituent of the Total Protein in the blood. It is manufactured in the liver, and released into the blood, where it has many functions, including the transport of a number of hormones around the body. Low serum levels are typically found with liver disease. The presence of albumin in the urine is a sign of kidney disease normally, large molecules like proteins are retained in the blood, but when the kidneys are damaged, proteins can leak through in to the urine (also see Microalbumin test). 1

9 Aldolase Aldolase is an enzyme that helps break down sugars to produce energy. It is found at high levels in the muscles, and elevated levels in the blood are indicative of muscle damage. The CK test is more commonly run to assess muscle damage, but there are certain conditions, such as muscular dystrophy, where aldolase is still used. Alkaline Phosphatase (ALP) ALP is an enzyme found at high levels in the liver and bones. Increased levels in the blood usually indicate disorders, including cancers, of the liver or bones. If other liver function tests (e.g. GGT, ALT, AST, Bilirubin) are also abnormal, this suggests that the ALP is coming from the liver. If tests such as Calcium and Phosphate are abnormal, this suggests that the ALP is coming from the bones. Aluminium Normally, the entire dietary intake of aluminium is eliminated by the kidneys. Serum levels are measured in kidney dialysis patients, who are at risk of aluminium toxicity, which can damage the brain and bones. Aluminium elevations may also be seen in patients with prosthetic joints containing aluminium. ALT (Alanine Aminotransferase) ALT is an enzyme found mainly in the liver, although smaller amounts are found in other tissues. It is primarily run, alongside other enzyme tests, as an assessment of liver damage. Ammonia Ammonia is a poisonous waste product produced by the body. It is carried to the liver, where it is broken down and converted into urea and glutamine. The urea is then removed by the kidneys. If this process doesn t work correctly, ammonia levels build up in the blood and pass into the brain. Symptoms like vomiting, irritability, tiredness and seizures can result. Amylase (Total & Pancreatic) Amylase is an enzyme made mainly by the pancreas. It is released into the digestive tract to help digest starch. When the pancreas is injured (e.g. when a patient is suffering from pancreatitis), increased amounts of amylase will be present in the blood, having been released from the damaged cells. AST (Aspartate Aminotransferase) AST is an enzyme found in liver, heart and skeletal muscle. When these muscle cells are injured, AST is released in to the blood. Although a general marker of tissue damage, AST is most commonly measured, alongside other enzymes, to assess liver disease. Bile Acids Bile Acids are produced in the liver, stored in the gall bladder and released into the intestine to aid digestion. After use, they are reabsorbed into blood bound for the liver and then returned to the gall bladder. If this cycle does not work correctly, e.g. in liver disease, bile acids will build up in the blood. Bile Acids may be measured as a sensitive marker of liver damage (levels are typically raised before those of other liver function tests), but its most common use is to diagnose the condition ICP (Intrahepatic Cholestasis of Pregnancy). This is a condition that restricts the flow of bile through the gall bladder, so bile acids build up in the liver and leak out into the bloodstream. 2

10 Bilirubin (Total & Direct) Bilirubin is a waste product from the breakdown of haemoglobin in the red blood cells. It is eliminated from the blood by the liver, and elevated levels in the blood can be an indicator of liver disease. Elevated levels of bilirubin cause jaundice (yellowing of the skin and whites of the eyes). Bilirubin is initially formed as unconjugated (indirect) bilirubin. It is transported to the liver, where it is converted into conjugated (direct) bilirubin, before being released into the bile and passing in to the intestine for removal in the stool. By determining the levels of direct and indirect bilirubin, it is possible to differentiate between different disease states. Elevated indirect bilirubin and decreased direct bilirubin indicate liver disease, because the liver cannot conduct effective conjugation. Normal indirect bilirubin and elevated direct bilirubin can indicate a bile blockage (liver function is unaffected). If both direct and indirect bilirubin are elevated, this can indicate excessive RBC breakdown (e.g. haemolytic anaemia). Labs will generally not have an assay to measure indirect bilirubin they will measure total and direct bilirubin and calculate the indirect. Cadmium Cadmium is a metal that is toxic in large quantities. It will generally be run as part of a heavy metal screen, along with other metals like copper, zinc, lead and cobalt. Heavy metal screening is most commonly done on individuals suspected of environmental exposure. Cadmium will be measured by methods like mass spectroscopy or atomic absorption. This may be done in a special chemistry lab, rather than in the routine Biochemistry setting. Calcium Calcium is one of the most important minerals in the body and is required for bone and teeth formation. It is excreted from the body by the kidneys, and is most often measured as an assessment of bone or kidney disease. Catecholamines Catecholamines are a group of hormones produced by the adrenal glands in the kidney. The main ones are Dopamine, Epinephrine (Adrenaline) & Norepinephrine (Noradrenaline). They are released during stress and have the effect of increasing the heart rate, widening the air passages in the lungs and increasing the release of glucose and fatty acids into the blood for energy. After use, catecholamines are metabolised into inactive compounds, as follows: Epinephrine Metanephrine & VMA (Vanillymandelic Acid) Norepinephrine Normetanephrine & VMA These compounds are removed from the body in the urine, where they are normally found in small concentrations. However, certain kidney tumours can produce large amounts of catecholamines; diagnosis of these is the main reason for catecholamine measurement. These tests are unlikely to be performed in the routine biochemistry setting; they are more likely to be run in a Special Chemistry or Biogenic Amine lab. 3

11 Cholesterol (Total Cholesterol, HDL Cholesterol, LDL Cholesterol, sldl Cholesterol) The various forms of cholesterol are measured as part of a cardiac risk assessment. HDL Cholesterol is sometimes known as the Good Cholesterol and levels have an inverse relationship with cardiac risk. LDL Cholesterol is sometimes known as the Bad Cholesterol and increasing levels indicate an increased risk of cardiac disease. The Total Cholesterol result will not give any indication of the HDL or LDL levels, but can be a useful initial screen, and can be used to indicate whether further lipid testing is required. LDL Cholesterol is made up of large buoyant and small dense forms. Current thinking is that the small LDL (sldl) Cholesterol is more atherogenic, as the small particles can more readily penetrate blood vessel walls, and that someone with high LDL, whose LDL is mainly the large buoyant form is actually at lower risk than someone with more moderate LDL levels, but whose LDL is mainly the small dense form. The sldl test is not yet routine, and will be run in a research setting and lipid specialist clinics. Cholinesterase Cholinesterase activity is measured to monitor poisoning from organic phosphates used in farming or in the chemical industry, or to identify patients likely to suffer prolonged effects from muscle relaxants used in surgery. Because the enzyme is synthesised in the liver, levels can also be abnormal in liver disease. There are 2 forms of the cholinesterase enzyme in the body acetyl and butrylcholinesterase. It is serum butrylcholinesterase (pseudocholinesterase) that is typically measured. Chromium Chromium is one of a group of tests known as Trace Element tests. Trace elements are minerals that the body needs in small amounts in order to carry out many different functions. Deficiencies can occur where there is an insufficient variety of food available, and therefore are rare in the developed world. There, deficiencies are more commonly due to conditions like coeliac disease that prevent absorption of nutrients from the gut. Excesses can also result, from over supplementation or from environmental exposure. Chromium will be measured by methods like mass spectroscopy or atomic absorption. This may be done in a special chemistry lab, rather than in the routine Biochemistry setting. Cobalt Cobalt is an essential element used in Vitamin B12 metabolism. However, deficiency does not occur in humans. Cobalt is used in various industries and toxicity can result from environmental exposure. Cobalt will be measured by methods like mass spectroscopy or atomic absorption. This may not be done in a special chemistry lab, rather than in the routine Biochemistry setting. Copper Copper is an essential mineral that is involved in many of the body s processes. The test is normally run to diagnose either copper deficiency or copper toxicity. The most common reason for testing is to diagnose Wilson s Disease, an inherited condition where copper accumulates in the brain, liver and other tissues. Most of the copper in the body is bound to caeruloplasmin, so the 2 tests are often requested together. 4

12 CK (Total) & CK-MB CK is an enzyme found mainly in cardiac and skeletal muscle. Blood levels will be elevated after muscle trauma. The enzyme is present in different forms in skeletal and cardiac muscle (CK-MM in skeletal muscle and CK-MB in cardiac muscle). Labs will have tests to measure Total CK and CK-MB i.e. they will not have a specific test for measuring the skeletal muscle form. Total CK will be elevated following either skeletal or cardiac muscle damage, and the CK-MB test can be used to pinpoint which of the 2 has occurred. CK-MB was used in the past to diagnose a heart attack, but this has been largely superseded by the Troponin test. The Total CK test may also be referred to as CK-NAC. Creatinine Creatinine is a waste product produced by muscle tissue. It is removed from the blood by the kidneys and excreted in the urine. If the kidneys are damaged, creatinine will build up in the blood. Creatinine is the main marker used to assess GFR (Glomerular Filtration Rate), the rate at which the kidneys filter waste products from the blood. However, creatinine results can be difficult to interpret because it is produced by muscle metabolism, serum levels are related to muscle mass, and the normal levels vary with gender, age, race and level of physical fitness. D-3-Hydroxybutyrate (Beta-Hydroxybutyrate) Ketones are by-products produced when fat is broken down and D-3-Hydroxybutytate is the major ketone body produced. The test is most commonly used in diabetes patients if a diabetic is unable to break down glucose, they will turn to breaking down fat as the next best energy source. This leads to the overproduction of ketones, the build up of which can ultimately lead to ketoacidosis, which is a medical emergency. This test may also be run in animals, particularly dairy cattle dairy cattle have a high energy requirement in order to produce milk, and can find themselves in a situation where their energy demand exceeds their glucose supply, leading on to a similar situation as that which can occur in a diabetic. Electrolytes Sodium, Potassium & Chloride Electrolytes are minerals that are found in the body as dissolved salts. As electrically charged particles, they help move nutrients into and waste out of cells, maintain a healthy water balance and help regulate the body s ph. Sodium, potassium and chloride are obtained from the diet and excreted by the kidneys. They are measured as part of a kidney function assessment and to monitor many acute and chronic conditions. ESR (Erythrocyte Sedimentation Rate) ESR is measured as a non-specific indicator of inflammation. The test measures the rate of fall of red blood cells (erythrocytes) in a thin tube after a period of time, the amount of clear plasma above the cells is measured. During inflammation, certain proteins (such as antibodies) are present in the blood at higher concentrations, causing the blood cells to fall more quickly and increasing the ESR. ESR may be measured in place of or in addition to CRP. 5

13 Fructosamine Fructosamine is a measurement of glycated serum proteins. It is used as a medium term monitor of blood glucose control in a diabetic. Excess glucose in the blood binds, in a permanent fashion, on to proteins in the blood. As the lifespan of serum proteins is 2-3 weeks, the fructosamine test provides an indicator of blood glucose control over the previous few weeks. There are certain situations where this test is more useful than HbA1c e.g. when evaluating response to a change in medication, you will get a faster answer by running fructosamine. Gamma GT Gamma GT is an enzyme found within the liver (it is used for the detoxification process). Under normal circumstances, serum levels should be low. However, in liver disease, GGT will be released from the damaged liver cells and blood levels increase. Glucose Glucose is a form of sugar and is the main energy source for most cells in the body. A diabetic patient is unable to break down glucose and levels build up in the blood. The blood glucose test is used to diagnose diabetes and for the on-going management of a diabetic s blood glucose levels. There are also various other conditions and medications that can affect blood glucose levels. Glucose-6-Phosphate Dehydrogenase (G6PD) G6PD is a protective enzyme found within red blood cells. Deficiency in the enzyme is inherited and can cause rapid red cell destruction, leading to haemolytic anaemia. This red blood cell lysis is particularly likely to occur after exposure to certain drugs and foodstuffs. GLDH (Glutamate Dehydrogenase) GLDH is an enzyme found within the mitochondria (energy producing machinery of cells). It is found in many tissues, but the biggest concentrations are found in the liver, and it is primarily run, alongside other liver function tests, to assess liver disease. Glutathione Peroxidase (GPx) Glutathione Peroxidase is an antioxidant. It is an enzyme that removes harmful free radicals from the body, preventing cell damage. The trace element selenium is needed to maintain GPx function, and GPx is often measured as an indicator of selenium status (it can be more useful than measuring selenium directly, because levels are less affected by sudden dietary changes). The Randox GPx assay is marketed under the brand name Ransel note that this is not a general term for a GPx assay. Glutathione Reductase Glutathione Reductase is an antioxidant that works alongside G-6-PDH to protect red blood cells from oxidative stress. Iodine Iodine is one of a group of tests known as Trace Element tests. Trace elements are minerals that the body needs in small amounts in order to carry out many different functions. Deficiencies can occur where there is an insufficient variety of food available, and therefore are rare in the developed world. There, deficiencies are more commonly due to conditions like coeliac disease that prevent absorption of nutrients from the gut. Excesses can also result, from over supplementation or from environmental exposure, e.g. from iodine containing drugs like amiodarone. Iodine will be measured by methods like mass spectroscopy or atomic absorption. This may be done in a special chemistry lab, rather than in the routine Biochemistry setting. 6

14 Iron, TIBC (Total Iron Binding Capacity) & UIBC (Unsaturated Iron Binding Capacity) Iron is an essential nutrient it is needed for the formation of haemoglobin, the oxygen carrying protein in red blood cells. Low levels of iron can lead to anaemia. Iron status tests are run to determine the amount of iron in the blood, the body s ability to transport iron and the amount of iron in storage. The Serum Iron test measures the amount of iron bound to transferrin (iron transport protein). TIBC measures the proteins available to bind with iron it is an indirect measurement of transferrin, as transferrin is the primary iron binding protein. TIBC will be cheaper to run than transferrin, and labs will typically run one test or the other. UIBC is a measurement of the number of transferrin sites not carrying iron. I.e. TIBC = UIBC & Serum Iron. See additional information on transferrin and ferritin (iron storage protein) in the Immunology section. Lactate / Lactic Acid Lactic Acid is a by-product produced during anaerobic energy production (i.e. when cellular oxygen is low and the body must turn to this less efficient method of generating energy). If lactic acid is produced at a rate faster than the liver can remove it, it can lead to lactic acidosis, which interrupts the body s acid-base (ph) status and can be a medical emergency. The test may be run in acute situations, but can also be used to monitor response to conditions like congestive heart failure (CHF), which lead to reduced flow of oxygenated blood around the body. LDH (Lactate Dehydrogenase) LDH is an enzyme found in almost all body tissues. Serum levels are normally low, but when tissue damage occurs, LDH will be released into the blood. The test is run as a general indicator of tissue damage. Lead Lead is a poisonous metal. Elevated blood levels can result from environmental exposure. In the past, lead was found in petrol, paints and other household products, and it can still be found in e.g. older housing. Lead toxicity can lead to developmental delays in children and can cause nerve damage and fertility problems. Lead will be measured by methods like mass spectroscopy or atomic absorption. This may be done in a special chemistry lab, rather than in the routine Biochemistry setting. Lipase Lipase is an enzyme produced by the pancreas. It is involved with the digestion of fat. Elevated levels can be due to various diseases of the pancreas and other parts of the intestinal tract. Low levels can be due to damage to the lipase producing cells, by e.g. cystic fibrosis. Magnesium Magnesium is a mineral that is essential for many of the body s functions. Blood levels of magnesium are regulated by how much is absorbed from food by the intestines and how much is removed by the kidneys. Abnormal levels are most commonly caused by conditions that affect kidney function and cause poor absorption. 7

15 Manganese Manganese is an essential trace element. However, toxicity can result in nerve damage. Toxicity is normally as a result of environmental exposure Manganese is used in steel production and processes used here result in airborne dust, which can be inhaled by miners and other workers in these industries. Manganese will be measured by methods like mass spectroscopy or atomic absorption. This may be done in a special chemistry lab, rather than in the routine Biochemistry setting. Molybdenum Molybdenum is an essential trace element, needed for nitrogen metabolism. It is widely distributed in the environment and in plant materials, so deficiency is rare. Toxicity is also rare, and is usually as a result of mining exposure. Elevations can also be seen in patients with metallic prosthetic joints. The test may be run as part of a trace metals screen. Molybdenum will be measured by methods like mass spectroscopy or atomic absorption. This may be done in a special chemistry lab, rather than in the routine Biochemistry setting. NEFA (Non Esterified Fatty Acids) The measurement of NEFA or free fatty acids can be used in the assessment of an uncontrolled diabetic. It is however, a more common animal test, particularly for dairy cows, where elevated levels of free fatty acids indicate that the animal is metabolising too much fats and that glucose intake is insufficient to meet the high energy demand. Nickel Nickel is used in many different industries, and levels are measured in blood and urine to detect toxicity due to environmental exposure. The major problems are caused by inhalation. Allergic skin reactions due to e.g. nickel in jewellery are not connected to blood levels. Nickel will be measured by methods like mass spectroscopy or atomic absorption. This may be done in a special chemistry lab, rather than in the routine Biochemistry setting. Nitrites This will be run as a urinalysis dipstick test to aid in the diagnosis of a urinary tract infection. Certain types of bacteria that cause UTIs can convert nitrates (normally found in the urine) to nitrites. Osmolality Osmolality is a measure of the number of particles dissolved in the blood or urine. It is measured to assess water balance and whether the body is able to react appropriately to changes in water balance (i.e. whether the kidneys are able to conserve water and concentrate urine in response to dehydration and vice versa). It may also be measured where ingestion of a toxin (e.g. methanol) is expected, as this will increase the level. Osmolality is measured on a dedicated instrument known as an osmometer. Oxalate Oxalate is one of a number of substances that typically make up kidney stones. It is measured as a urine test, and high levels in the urine indicate that a patient is at increased risk of developing kidney stones. 8

16 Phosphate Phosphate is required for energy production and bone development. Phosphate is obtained from the diet and the body maintains a healthy balance by controlling the amount that is absorbed through the intestines and the amount excreted by the kidneys. Abnormal results can indicate kidney damage or gastrointestinal / malnutrition conditions that affect uptake. Protein (Total) This refers to the combined measurement of albumin and globulin proteins in the blood. These proteins all have vital functions in the body. Low levels of Total Protein can be indicative of liver disease (since the liver is the site of production of many proteins), kidney disease (a healthy kidney filters wastes but maintains proteins in the blood; kidney disease causes proteins to be lost in to the urine) or malabsorption conditions, where protein is not taken up from the diet. Protein Electrophoresis While the lab will measure levels of Albumin and Total Protein and various other serum proteins individually, using the routine biochemistry analyser, an electrophoretic breakdown of the proteins in a serum or CSF sample can also be measured. This looks at the relative proportions of albumins, alpha-1-globulins, alpha-2-globulins, beta globulins and gamma globulins. Serum electrophoresis may be done to diagnose and monitor immune system disorders and plasma cell cancers like multiple myeloma, which results in the excessive production of a specific type of immunoglobulin. CSF protein electrophoresis may be done to identify protein variations seen in multiple sclerosis or viral illnesses. The test involves using an electrical current to move proteins along a thin layer of gel. The distance that individual proteins travel depends on their size, shape and electrical charge. A protein binding dye is used to reveal a pattern of bands, with each one corresponding to a particular protein. The size of each band indicates the concentration of the protein. Selenium Selenium is an essential element. It is required to maintain the activity of the antioxidant Glutathione Peroxidase. Selenium deficiency correlates with cell damage due to free radical accumulation. Toxicity is rare, but can result from over supplementation or from environmental exposure. Blood levels may be measured to identify either deficiency or toxicity. Selenium is often measured with other trace elements, such as iron, zinc and copper. Selenium will be measured by methods like mass spectroscopy or atomic absorption. This may be done in a special chemistry lab, rather than in the routine Biochemistry setting. Glutathione Peroxidase (GPx) is also measured as an indicator of selenium status it is useful because levels are not significantly affected by sudden dietary changes in the way that selenium levels are. Superoxide Dismutase (SOD) Superoxide Dismutase is an antioxidant. It is an enzyme that catalyses the breakdown of the harmful free radical superoxide. The Randox Superoxide Dismutase assay is marketed under the brand name Ransod note that this is not a common market term for the test. 9

17 Thallium Thallium is found in insecticides and rodenticides. Blood or urine levels may be measured as part of a heavy metal screen in someone suffering from toxic side effects. Thallium will be measured by methods like mass spectroscopy or atomic absorption. This may be done in a special chemistry lab, rather than in the routine Biochemistry setting. Triglycerides Triglycerides are the most abundant form of fat stored by the body. Elevated triglyceride levels are associated with cardiovascular disease risk. The triglyceride test forms part of the standard lipid profile assessment. Urea Urea is a waste product from protein metabolism. It is removed from the blood by the kidneys and excreted in the urine. Elevated levels in the blood are therefore indicative of kidney damage. Uric Acid Uric Acid (Urate) is a waste product from the breakdown of purines (the building blocks of DNA). The kidneys are responsible for removing uric acid from the blood and excreting it in the urine. A buildup of uric acid in the blood can cause crystals to form in the joints, leading to gout, and is indicative of kidney disease. Urobilinogen This will be run as a urinalysis dipstick test. Urobilinogen is formed from the breakdown of bilirubin in the intestines. Some of it is absorbed back in to the blood, from where it passes through the kidneys, into the urine. Normally, levels in the urine are low. Elevated levels can indicate liver disease or a condition like haemolytic anaemia that causes increased red blood cell destruction (see separate entry on bilirubin for an explanation on its association with liver function). Zinc Zinc is an important mineral that is involved in many of the body s processes. Levels are measured to diagnose either zinc deficiency (which is relatively common, and can result from a number of different diseases) or zinc toxicity (which can result from over supplementation). 10

18 Immunoassay analytes The following tests are all run on immunoassay analysers. They may be run in an Endocrinology Lab, but it is becoming increasingly more common for them to be run in the core Biochemistry lab, particularly where integrated and modular systems are installed (i.e. with chemistry and immunoassay consolidated onto a single platform or on linked platforms). Immunoassay analysers are all closed systems assays will only be supplied by the instrument suppliers, and Randox cannot supply any standard reagents (although, some of these tests will be available on the Biochip (Evidence) platforms). However, Randox does supply either internal quality control sera or RIQAS programmes for all of the following tests (and in most cases, both IQC and RIQAS). The below key indicates the sample type that will be tested and whether we have control materials or RIQAS programmes available. Note that many of the below analytes will be present in multiple QC sera / RIQAS programmes. Serum / plasma test Urine test Whole blood test Randox IQC available RIQAS programme available 17-OH-Progesterone 17-OH-Progesterone may also be referred to as 17-Hydroxy Progesterone. It is a steroid hormone that is used by the body to make cortisol. It is measured to diagnose conditions that affect the adrenal gland, such as Congenital Adrenal Hyperplasia or adrenal tumours. ACTH ACTH stands for Adrenocorticotropic Hormone, but will typically only be referred to as ACTH. It is produced by the pituitary gland and stimulates production of cortisol by the adrenal gland ACTH levels generally rise when cortisol is low and decrease when cortisol is high. The ACTH test is often run in patients with abnormal levels of cortisol, to help narrow down the cause. AFP (Alphafetoprotein) AFP is a type of tumour marker test. It is a protein produced during foetal development and liver cell regeneration. Levels fall soon after birth and are typically very low in men and non-pregnant women. Cancers of the liver, testes and ovaries can produce high levels of AFP. However, elevated levels do not necessarily mean that cancer is present, because liver damage can also cause elevated levels. Like with other tumour marker tests, AFP is generally run to monitor the success of therapy. Pregnant women have higher levels, due to production by the baby. In addition to AFP being used as a tumour marker test, it is also run as one of a number of maternal screening serum tests used to assess the risk of a foetus suffering from Down Syndrome and other chromosomal abnormalities. 11

19 Aldosterone The Aldosterone test is usually run alongside the Renin test. Both are hormones involved in regulating the blood pressure. The tests may be requested in individuals with high blood pressure; results can point to the treatments that will likely be effective. Androstenedione Androstenedione is a hormone produced by the adrenal glands, testes and ovaries. It considered to be a male sex hormone, and is responsible for development during puberty. In females, elevated levels cause the development of male characteristics (e.g. excess hair). The test is run to evaluate the function of the adrenal glands, ovaries and testes. It is most often requested when the results of a testosterone test are abnormal. Anti-TG (Anti-thyroglobulin) & Anti-TPO (Anti-thyroperoxidase) Anti-TG and Anti-TPO are both thyroid antibodies. They are both autoantibodies i.e. antibodies produced by the body that attack its own tissue. These tests are run to help diagnose autoimmune thyroid disease. They may also be run in patients suffering from other autoimmune diseases, such as Lupus or Rheumatoid Arthritis. β-2-microglobulin β-2-microglobulin is a protein whose levels rise in patients with cancers like multiple myeloma and lymphoma. In these patients, it is normally used to predict prognosis and to monitor the effectiveness of treatment. Levels may also be increased in certain inflammatory conditions and in kidney disease. BNP / NT-proBNP B-Type Natriuretic Peptide / N-Terminal-proBNP are both markers of congestive heart failure (CHF). They are measured to diagnose and assess the severity of heart failure. This is a progressive condition, where the heart becomes less and less able to pump blood around the body. Whenever the heart has to work harder, more BNP is released in to the blood. Both tests are run for the same purpose; whether a lab runs BNP or NT-proBNP depends on their analyser installations some machines offer the BNP test while others offer the NT-proBNP test. CA125 The term CA125 refers to Cancer Antigen 125. This is a protein secreted by ovarian cancer cells. It is one of a number of commonly run tumour marker tests. It is used to monitor therapy during treatment for ovarian cancer if levels fall during therapy, this generally indicates that the cancer is responding to treatment. Levels that start to increase after treatment is complete can indicate a recurrence. Like many tumour markers, this test is not useful for ovarian cancer screening CA125 can be elevated in a number of benign conditions, such as pregnancy and normal menstruation, endometriosis and pelvic inflammatory disease. 12

20 CA15-3 The term CA15-3 refers to Cancer Antigen It is a protein produced by breast tissue and is one of a number of commonly run tumour marker tests. CA15-3 is not sensitive or specific enough to be considered useful as a tool for cancer screening levels will not be elevated in the majority of early cancers, and levels can be elevated in other forms of cancer and certain benign conditions. Its main use is in monitoring a patient s response to breast cancer treatment and to watch for breast cancer recurrence. CA19-9 The term CA19-9 refers to Cancer Antigen It is one of a number of commonly run tumour marker tests. Elevated levels may be associated with colorectal, stomach, ovarian, liver or pancreatic cancer. However, it is not sensitive or specific enough to be used as a screening test (levels can be elevated by a number of benign conditions), and like other tumour markers, its main use is to monitor treatment and to watch for recurrence. CA72-4 CA72-4 is a newer tumour marker test associated with gastric (stomach) cancer. It is not as commonly run as CA15-3 / CA19-9 / CA125 and other tumour markers, such as AFP and CEA. CA27.29 CA27.29 is a tumour marker produced by certain types of breast cancer. Like all tumour marker tests, it is not used to diagnose or screen for breast cancer. It is used to monitor the effectiveness of treatment and to check for recurrence. The test may be ordered alongside the CA15-3 test, although CA27.29 will not be run in as many laboratory sites as CA15-3. Calcitonin Calcitonin is a hormone produced by the thyroid gland. It is elevated in patients suffering from thyroid cancers. Calcitonin is a tumour marker run to monitor response to therapy and to detect recurrence. CEA Carcinoembryonic Antigen CEA is a protein found in developing embryos. By adulthood, levels in the blood tend to be very low. Elevated levels may be associated with a number of different cancers, but can also be caused by a number of benign conditions. Levels can also be higher in smokers. Therefore, an elevated level of CEA does not provide a definitive cancer diagnosis, and as with other tumour markers, the test is generally run to measure response to therapy and check for recurrence. Cortisol Cortisol is a steroid hormone produced by the adrenal gland. Its production is stimulated by the hormone ACTH. Cortisol helps to regulate the immune system and glucose, protein and lipid metabolism, and levels also increase is response to stress. Abnormally low levels of cortisol can indicate an underactive adrenal gland or underactive pituitary gland (since ACTH is produced by the pituitary). Abnormally high levels of cortisol can indicate adrenal or pituitary gland tumours. 13

21 C-Peptide C-Peptide is a hormone stored in the pancreas. When insulin is released into the blood for glucose metabolism, C-Peptide is released at the same time. It is therefore a useful marker of insulin production. When insulin levels are measured, C-Peptide can be used to differentiate between insulin produced by the pancreas and injected insulin. In a newly diagnosed diabetic, C-Peptide can be measured to determine the type of diabetes in a Type 1 diabetic, insulin is not produced in sufficient quantities, so C-Peptide is also low. Type 2 diabetes is also known as insulin resistance diabetes, meaning that insulin and C-Peptide are still produced. Cyfra 21-1(CYtokeratin 19 FRAgments) Cyfra 21-1 is a protein that will be elevated in patients suffering from certain types of lung cancer. Like the majority of tumour markers, it is used in diagnosed patients to monitor response to therapy and detect recurrence. D-dimer D-dimer is a protein that is produced when a blood clot is broken down (after an injury has had time to heal, the clot is broken down so that it can be removed). D-dimer is normally undetectable in the blood, as it is produced only when a clot is in the process of being broken down. It is measured in patients exhibiting symptoms of abnormal clot formation, such as DVT (Deep Vein Thrombosis) or Pulmonary Embolism. D-dimer is a test with excellent negative predictive value i.e. a negative result rules out a clot, but a positive result does not provide a definitive diagnosis. The D-dimer test is offered on many Immunoassay systems, but may also be run as a coagulation test. DHEA-Sulphate DHEA-Sulphate is a male sex hormone produced by the adrenal gland. It is measured to evaluate adrenal function, adrenal tumours, the development of male physical characteristics in females (excess hair etc.) or early puberty in boys. These conditions may be present when DHEA-S is elevated. Abnormally low levels may point to adrenal gland dysfunction or dysfunction of the pituitary gland (since DHEA-S secretion is controlled by the pituitary hormone ACTH). Ferritin Ferritin is an iron storage protein. The test may be ordered, along with other iron status tests, in a patient suffering from symptoms suggestive of iron deficiency anaemia e.g. chronic tiredness, weakness, dizziness, headaches & pale skin. Depending on the hospital, ferritin may be run as an immunoassay or a protein / immunology test. Folate Folate is one of the B Vitamins. Deficiency causes a form of anaemia where the body produces abnormally large red blood cells that cannot function properly. The test may be done to help diagnose the cause of anaemia. Deficiency can be due to insufficient dietary intake or conditions, like coeliac disease, that inhibit uptake. Labs may measure folate levels in both serum and inside the red blood cells (red cell folate). 14

22 FSH (Follicle Stimulating Hormone) FSH is a hormone produced by the pituitary gland. It is one of a number of commonly measured fertility hormones. In females, it stimulates the development of ovarian follicles (eggs) and is measured as part of an infertility assessment. It can also be used to determine if a woman has reached menopause. In males, it supports the development of sperm and is also measured as part of a fertility assessment. High levels can indicate menopause or primary ovarian / testicular failure. Low levels can point to an underactive pituitary gland. Gastrin Gastrin is a hormone that regulates the production of stomach acid. Certain conditions cause excess gastrin production, leading to stomach ulcers. Excess levels of gastrin can also be due to gastrin producing tumours. Growth Hormone GH is required for normal bone development and growth in children. Levels are measured in people exhibiting symptoms of growth hormone abnormalities i.e. either excessive or delayed growth. hcg (Human Chorionic Gonadotropin) hcg is a hormone produced during pregnancy. Qualitative (reported as positive or negative) hcg tests are routinely run on urine to confirm pregnancy. These tests are done in Point of Care situations and in the home. Quantitative hcg tests done in the lab (on both serum and urine) measure the amount of hcg present. These can be done to diagnose an abnormal pregnancy, such as an ectopic pregnancy, or to monitor a pregnancy that may be failing. hcg can also be measured as a tumour marker test, because the hormone is produced by certain cancers elevations in the absence of pregnancy can point to cancer. hcg is also run as one of a number of maternal serum screening tests used to assess the risk of an unborn baby having Down Syndrome or other chromosomal abnormalities. Inhibin A Inhibin A is one of the tests (along with hcg, AFP and Unconjugated Oestriol) that make up the maternal screening test known as the Quad Screen. This is a panel of tests run during the second trimester of pregnancy to assess the risk of the foetus having Down Syndrome or other chromosomal abnormalities. Insulin Insulin is a hormone required for the metabolism of glucose. The test may be ordered to determine the cause of low blood glucose, diagnose an insulin producing tumour or to help evaluate insulin production in a diabetic for this purpose, insulin is run alongside C-Peptide. When insulin is released by the pancreas, C-Peptide is also released measuring C-Peptide alongside insulin therefore enables the assessment of how much of the measured insulin has been produced by the body and how much has come from injected insulin. 15

23 Insulin Like Growth Factor (IGF-1) This protein is also known as Somatomedin C. It is related to Growth Hormone (GH) and is run in individuals exhibiting either excessive or delayed growth. Generally, the levels of IGF-1 mirror those of GH. However, GH levels fluctuate throughout the day, whereas IGF-1 levels do not. The IGF-1 test may therefore provide a better estimation of the average Growth Hormone levels. LH (Luteinising Hormone) LH is a hormone produced by the pituitary gland. It promotes the production of male and female sex hormones and is one of a number of commonly run fertility hormone tests. LH is measured as part of the investigation into infertility. Elevated levels can indicate ovarian or testicular failure and low levels can indicate pituitary gland dysfunction. Neuron Specific Enolase (NSE) NSE is a protein that may be elevated in patients with small cell lung cancer and a number of other cancers. It is measured as a tumour marker to monitor disease progression and treatment in these patients. Oestradiol Oestradiol (Estradiol in the USA) is one of 3 naturally produced oestrogens. It acts to promote the development of and to maintain the female reproductive system. In females, it is measured to help evaluate ovarian function and investigate infertility. Levels vary throughout the menstrual cycle, reaching their peak at ovulation. Levels gradually decrease throughout adulthood, and are at their lowest after menopause. Males also produce oestradiol, but at much lower levels. Elevated levels in males can lead to the development of female characteristics. Oestriol, Unconjugated Unconjugated Oestriol (Estriol in the USA), also known as UE3, is another oestrogen hormone. It is one of a number of tests run as part of the 2 nd trimester maternal serum screen (Triple Test / Quad Test) to assess the risk of an unborn baby having Down Syndrome or other chromosomal abnormalities. Osteocalcin Osteocalcin is a protein found in bone. It is used as a marker for the bone formation process higher serum levels of osteocalcin are correlated with increased bone density. PAPP-A PAPP-A (Pregnancy Associated Plasma Protein A) is a test run alongside the Free Beta hcg test in the Double Test, a maternal screening test used in the first trimester of pregnancy to assess the risk of Down Syndrome and other chromosomal abnormalities in the foetus. Procalcitonin Procalcitonin (PCT) is a protein produced during systemic bacterial infection, or sepsis. It is not elevated in localised bacterial infections or in viral infections. The test is run on critically ill patients to distinguish between bacterial infections and other causes of serious illness. It can, for example, be run to help diagnose or to rule out bacterial meningitis. 16

24 Progesterone Progesterone is a fertility hormone. It is produced during the luteal phase of the menstrual cycle (this is the second half of the cycle, starting after ovulation, when the uterus is prepared for implantation of an embryo). Levels will vary throughout the menstrual cycle they usually start to elevate when an egg is released from the ovary, rise for several days, and then either continue to rise with early pregnancy or fall to initiate menstruation. One of the main reasons for the measurement of progesterone is as part of an infertility assessment if levels do not rise and fall on a monthly basis, a woman may not be ovulating. Prolactin Prolactin is a hormone produced by the pituitary gland. It typically occurs at low levels in men and in non-pregnant women. In females, levels rise during pregnancy and promote lactation. Levels remain high while a woman is breast-feeding. In males and in females who are not pregnant / breast feeding, high levels can indicate cancer of the pituitary gland and a number of other conditions. Low levels can indicate an underactive pituitary. Prolactin is often considered to be a tumour marker test levels may be measured to monitor response to treatment for a prolactinoma (pituitary tumour that secretes prolactin). PSA (Prostate Specific Antigen) PSA is a Tumour Marker test. Labs will measure both Total and Free PSA. Total PSA is measured as a prostate cancer screening test. Elevated tpsa can indicate cancer. However, the results are not definitive, as PSA can also be elevated due to infection or other benign prostate conditions. The Free PSA test may be ordered when Total PSA levels are mildly elevated, as this helps to differentiate between cancerous and non-cancerous conditions in a patient with prostate cancer, the ratio of free to bound PSA is typically lower. There is some controversy over the use of the PSA test, both because of its association with noncancerous conditions, and because it can lead to the diagnosis and aggressive treatment of slow growing tumours that would never be life threatening. PTH (Parathyroid Hormone) PTH regulates the amount of calcium in the blood. If blood calcium is low, PTH is released from the parathyroid glands, and increases blood calcium by causing its release from the bones, increasing uptake from the intestines and suppressing urinary excretion. The test is run to help diagnose the cause of high or low blood calcium. It will always be requested alongside a calcium test (general chemistry assay). Renin The renin test is usually run alongside the Aldosterone test. Both are hormones involved in regulating the blood pressure. The tests may be requested in individuals with high blood pressure; results can point to the treatments that will likely be effective. 17

25 SHBG (Sex Hormone Binding Globulin) SHBG binds and transports sex hormones, including testosterone. It will be ordered alongside a testosterone test, particularly when the total testosterone results don t agree with clinical signs. If SHBG is too high, then it binds much of the testosterone in the body, leaving little free testosterone to act on the body this can lead to low libido and infertility in men. If SHBG is too low, then much of the testosterone in the body remains unbound, as free testosterone. In females, this leads to the development of more masculine characteristics, such as excess hair growth. T3 (Tri-iodothyronine) / FT3 (Free Tri-iodothyronine) T3 is one of 2 main hormones produced by the thyroid gland and is involved in regulating the body s metabolism. It is one of a group of tests known as TFTs (Thyroid Function Tests). A high level of Free or Total T3 may indicate an overactive thyroid gland (hyperthyroidism), while a low level of Free or Total T3 may indicate an underactive thyroid gland (hypothyroidism). T4 (Thyroxine) / FT4 (Free Thyroxine) T4 is one of 2 main hormones produced by the thyroid gland and is involved in regulating the body s metabolism. It is one of a group of tests known as TFTs (Thyroid Function Tests). A high level of Free or Total T4 may indicate an overactive thyroid gland (hyperthyroidism), while a low level of Free or Total T4 may indicate an underactive thyroid gland (hypothyroidism). The test may also be used to help evaluate a patient with an enlarged thyroid gland (goitre) iodine is necessary for thyroid hormone production and an iodine deficiency can lead to this condition. Testosterone Testosterone is a steroid hormone produced by the testes in males and the adrenal glands and ovaries in women. It is generally considered to be a male sex hormone and is present in women at much lower levels. In women, increased testosterone levels may be associated with ovarian or adrenal gland tumours or PCS (polycystic ovary syndrome). Overproduction of testosterone in women can also lead to excessive growth of body hair and absence of menstrual periods. In men, testosterone stimulates sperm production. Increased testosterone production may be associated with certain tumours, while low levels can indicate infertility. Thyroglobulin Thyroglobulin is a protein produced by and stored in the thyroid gland. It is broken down to produce the thyroid hormones T3 and T4, when required. However, many thyroid cancers produce thyroglobulin and it is mainly measured as a tumour marker test to monitor response to therapy for thyroid cancers and to detect recurrence. Troponin Cardiac troponins are proteins found in heart muscle. They help to regulate the heartbeat. Under normal circumstances, the levels in the blood should be very low. However, if an individual suffers a heart attack (Acute Myocardial Infarction / AMI), troponin will be released from the damaged heart cells into the blood. Detection of troponin in the blood is the current confirmatory test for a heart attack. The test will be ordered on any chest pain patient brought in to a hospital s emergency department. Levels will remain elevated for 1-2 weeks, so the troponin test can also be used to confirm a heart attack that has taken place previously. Labs will measure either Troponin I or Troponin T. The assay in use will depend on the analyser they have and its test menu offering. 18

26 TSH (Thyroid Stimulating Hormone) TSH is a hormone produced by the pituitary gland. It is one of a group of tests, known as TFTs or Thyroid Function Tests, that are run to assess the function of the thyroid gland. TSH acts on the thyroid gland to control the production of thyroid hormone when thyroid hormone concentrations in the blood rise, TSH production decreases and vice versa. Therefore, a low level of TSH in the blood suggests that the patient has an overactive thyroid (a condition known as hyperthyroidism) and a high level of TSH in the blood suggests that the patient has an underactive thyroid (a condition known as hypothyroidism). TSH Receptor Antibody (TRAb) TRAb is an autoantibody (i.e. an antibody produced when the immune system recognises the body s own tissue as foreign). The main reason for running the test is to diagnose Grave s Disease, an autoimmune disease of the thyroid gland that leads to hyperthyroidism. T-Uptake The T-Uptake test is one of the thyroid hormone tests. It provides a measurement of the amount of protein available to bind thyroid hormones. It is less common than the other TFTs (thyroid function tests), and is generally only run to help evaluate the situation when levels of T3 and T4 are abnormal. Vitamin B12 Deficiency in this vitamin can lead to a form of anaemia, where the red blood cells are abnormally large. Vitamin B12 is measured to diagnose the condition and to monitor individuals undergoing treatment for B12 deficiency. Dietary deficiency of Vitamin B12 is rare; deficiency is normally caused by one of a number of conditions that prevent uptake of the vitamin through the stomach lining, hence the need for medical treatment (OH 2 ) Vitamin D 1-25-(OH 2 ) Vitamin D, or 1-25-Dihydroxy Vitamin D, is a measurement of the active form of Vitamin D. The kidneys are responsible for converting the inactive form of Vitamin D (25-OH-Vitamin D) to the active form. This test is run as a kidney function test to check whether the kidneys are performing this conversion correctly. When Vitamin D tests are run to assess bone health, it is the inactive form that is measured, because it is the Vitamin D stores that are of more interest. 25-OH-Vitamin D Vitamin D is required for the growth and health of bone. The test may be ordered when a deficiency is suspected. 25-OH-Vitamin D (25-Hydroxy-Vitamin D) is the inactive form of the Vitamin. This is the form most commonly measured, because it is generally the body s vitamin D stores that are of interest, and these are reflected by levels of the inactive form of the vitamin. 19

27 Immunology analytes The following tests may also be known as Specific Protein tests. They are all run by immunoturbidimetric (IT) or nephelometric methods. These tests may be run in a separate Immunology Lab, but it is becoming increasingly more common for them to be run in the core Biochemistry lab, particularly as IT methods are run on the standard Biochemistry analyser. Nephelometric methods are run on dedicated closed systems (typically the Beckman Immage or Siemens BN systems). It is likely that labs that use a nephelometer will also be running some of the higher throughput protein tests, like CRP, by IT on their chemistry analyser (nephelometers are slower systems and may not be able to cope with the higher volume tests). Randox supplies a range of IT assays. Some of the below protein tests will only be available as nephelometric methods. However, Randox still has these available as quality control and RIQAS analytes. The below table indicates the sample type the test is run on, whether Randox supplies a reagent, and whether IQC / RIQAS is available. Note that many of these analytes will be present in multiple IQC sera / RIQAS programmes. Serum / plasma test Urine test Whole blood test Randox reagent available (IT method with the exception of Anti-thrombin III) Randox IQC available RIQAS programme available Adiponectin Adiponectin is a hormone secreted by fat cells. Low levels are associated with obesity and can be correlated to the risk of developing Type 2 Diabetes. AFP (Alphafetoprotein) AFP is a type of tumour marker test. It is a protein produced during foetal development and liver cell regeneration. Levels fall soon after birth and are typically very low in men and non-pregnant women. Cancers of the liver, testes and ovaries can produce high levels of AFP. However, elevated levels do not necessarily mean that cancer is present, because liver damage can also cause elevated levels. Like with other tumour marker tests, AFP is generally run to monitor the success of therapy. Pregnant women have higher levels, due to production by the baby. In addition to AFP being used as a tumour marker test, it is also run as one of a number of maternal screening serum tests used to assess the risk of a foetus suffering from Down Syndrome and other chromosomal abnormalities. α-1-antitrypsin AAT deficiency is an inherited condition that can lead to lung and liver disease. The protein is produced by the liver and released into the blood, from where it offers protection to the lungs. Patients with a deficiency produce a mutated form of the protein, which is not able to be released from the liver cells this build up within the liver causes damage to the liver, while the decreased blood levels lead to lung damage. 20

28 α-1-acid Glycoprotein AAG is also known as orosomucoid. It is an acute phase reactant (a protein whose levels alter in response to inflammation). Levels will be elevated in a number of conditions, including cancers, that are associated with inflammation. α-2-macroglobulin α-2-macroglobulin is a large protein made by the liver. It acts as a carrier protein for many different molecules. When a patient is suffering from nephrotic syndrome (kidney disease), proteins are lost through the kidneys, into the urine. Because α-macroglobulin is a large protein, it does not pass through the kidneys and serum concentrations rise. This increase does not itself cause any illness, but can point to the diagnosis of nephrotic syndrome. Apolipoproteins A-1 and B Apolipoproteins enable cholesterol to be carried round the bloodstream. Apo A-1 is associated with HDL Cholesterol and levels are therefore inversely associated with cardiac risk. Apo B is associated with LDL Cholesterol and levels are therefore directly associated with cardiac risk. Measuring the ratio of Apo B / Apo A-1 is seen as a superior predictor of cardiac risk than HDL and LDL Cholesterol although most Apo B in the body is in LDL, it is also found in VLDL (Very Low Density Lipoprotein) and Lp(a), and therefore its measurement covers all the atherogenic lipoproteins. Apolipoproteins A-II, C-II, C-III & E These special lipoproteins are all associated in different ways with atherosclerosis risk and levels of cholesterol and triglycerides. As yet, none are routine tests; they will only be run in lipid specialist clinics. Levels may also be associated with diseases other than CVD, and these tests may also be run in a research setting. ASO (Antistreptolysin O) Antistreptolysin O is an antibody produced against Streptolysin O, which is a toxin produced by Group A streptococcal bacteria. The test is used to diagnose streptococcal infections (e.g. strep throat) and complications of infections, which can lead to heart or kidney damage. Anti-thrombin III Anti-thrombin is a protein that helps control blood clotting it inhibits the action of several other clotting factors to prevent excessive clot formation / thrombosis. Patients with an anti-thrombin deficiency are at increased risk of thrombosis. This test may be run as a protein assay on a nephelometer, but can also be run on coagulation analysers, which are generally located in a hospital s Haematology department. β-2-microglobulin β-2-microglobulin is a protein whose levels rise in patients with cancers like multiple myeloma and lymphoma. In these patients, it is normally used to predict prognosis and to monitor the effectiveness of treatment. Levels may also be increased in certain inflammatory conditions and in kidney disease. 21

29 Caeruloplasmin Caeruloplasmin is a protein that binds most of the copper in the blood. It is measured alongside copper to evaluate conditions of copper deficiency or toxicity. Its most common use is in the diagnosis of Wilson s disease this is a condition where excess copper is stored in various organs, with the result that caeruloplasmin levels will be low. Complement C3 & C4 Complement proteins work with the immune system to help destroy bacteria and viruses. C3 and C4 are measured to assess immune system health and to determine if a patient s disease condition is due to a deficiency in either of these proteins. CRP (C-Reactive Protein) CRP is an acute phase reactant. It is released by the liver into the blood following a tissue injury, infection or inflammation, and levels can rise rapidly in these situations. The test is not diagnostic for any particular condition, but it can indicate the level of inflammation present and can be used to monitor treatment. Labs may also measure High Sensitivity CRP (hscrp). Here, they are measuring the same protein, but at much lower levels, and will typically have a separate test that allows them to measure down to very low levels. With this test, CRP levels that remain within the normal range, but show slight increases, can point to low lying inflammation in the blood vessels this is seen as a cardiac risk factor. Cystatin C Cystatin C is a newer marker of kidney function. It is a protein that is produced by the majority of cells in the body. It is filtered from the blood by the kidneys and then broken down in the kidneys (i.e. not returned to the blood or excreted in the urine). If blood levels rise, this indicates impaired kidney function (reduced GFR Glomerular Filtration Rate). Cystatin C is not a routinely run test as yet. Creatinine is still the major marker used to assess GFR. However, as Cystatin C levels are not affected by age, gender or muscle mass, the test is easier to interpret and is therefore gaining interest. Ferritin Ferritin is an iron storage protein. The test may be ordered, along with other iron status tests, in a patient suffering from symptoms suggestive of iron deficiency anaemia e.g. chronic tiredness, weakness, dizziness, headaches & pale skin. Depending on the hospital, ferritin may be run as an immunoassay or a protein / immunology test. Haptoglobin Haptoglobin is a protein produced by the liver. Its role is to bind free haemoglobin in the blood, forming a complex that can be removed from circulation. Normally most haemoglobin is found within red blood cells; it is only found free when RBCs are being destroyed. Haptoglobin is measured to diagnose conditions like haemolytic anaemia that cause RBC destruction. Here, haptoglobin levels will decrease because the protein is being bound to haemoglobin and removed from circulation faster than the liver can produce it. 22

30 HbA1c Haemoglobin A1c is a diabetes monitoring test. Unlike other IT tests, it is run on a whole blood sample. The test measures the amount of glucose bound to haemoglobin (glycated haemoglobin) inside the red blood cells. The binding of glucose to haemoglobin is irreversible, and remains for the lifespan of the red blood cell. Therefore, the amount of glycated haemoglobin present is an indicator of how good a diabetic s blood glucose control has been over the previous 2-3 months. The test may be run up to 4 times per year on diagnosed diabetics. The test is now also starting to be used for diabetes diagnosis as well as monitoring. H-FABP (Heart-type Fatty Acid Binding Protein) H-FABP is a marker of AMI (Acute Myocardial Infarction / heart attack). It is a protein that is specific to the heart and, like Troponin, will be released from damaged heart muscle into the blood when a heart attack occurs. However, it is a smaller protein than Troponin and therefore, will be released into the blood more quickly and elevations are detected earlier on. This has impacts when it comes to both rule in and rule out scenarios i.e. a heart attack patient can be diagnosed more quickly and can be sent for stenting more quickly, improving their outcome, and, a chest pain patient who has not had a heart attack can be discharged more quickly. However, H-FABP is not widely run as yet, and where it is run, it will be run alongside Troponin for the foreseeable future there are no plans yet to replace Troponin as the confirmatory marker of a heart attack. Immunoglobulins (IgA / IgE / IgG / IgM) Immunoglobulin is another term for antibody. Ig levels are measured to assess immune system health. Measurement of the different classes of immunoglobulin can provide different information. IgA is a secretory antibody that protects mucosal areas (e.g. respiratory tract). IgE levels are associated with parasitic infections and allergic reactions. IgM is the initial antibody produced after infection, so levels will be elevated in early infection. IgG is the long lasting antibody that provides future protection from infection. Kappa & Lambda Light Chains (free and total) Light chains are run to help diagnose and monitor plasma cell cancers like multiple myeloma. Kappa and Lambda Light Chains are proteins produced by plasma cells that make up part of the structure of an antibody. If however, there is a malignancy in these plasma cells, causing them to divide uncontrollably, excessive light chain production can result. Lipoprotein(a) Lp(a), which is pronounced Lipoprotein little a, is measured as an independent cardiac risk factor. High levels of Lp(a) place an individual at higher risk of heart disease. Levels are inherited, and cannot be altered by dietary or lifestyle changes. 23

31 Microalbumin The microalbumin test is run on a urine sample and is used to diagnose early stage kidney damage. Normally, the filtration system in the kidneys removes waste products, whilst retaining necessary substances, like proteins, in the blood. However, if the kidneys are damaged, proteins will start to pass through and be excreted out in the urine. Measurement of levels of proteins like albumin in the urine provides evidence of the amount of kidney damage (note that albumin and microalbumin are the exactly same thing microalbumin just refers to small amounts of albumin and hence, early kidney damage. If albumin is being measured in the urine, it means that much higher concentrations of the protein are being detected, and kidney damage is more severe). The test is often run on diabetics, as kidney damage is one of the main complications of diabetes. Myoglobin Myoglobin is the oxygen carrying protein in muscle (both skeletal and cardiac muscle). Levels in the blood are normally very low, but following muscle damage, myoglobin is released into the blood, and levels will rise rapidly. Myoglobin may be run on a suspected heart attack patient elevations cannot be used to diagnose a heart attack, because they could also be due to skeletal muscle damage but a negative myoglobin test can rule out a heart attack. However, it is becoming uncommon for myoglobin to be run on cardiac patients. The test may also be run on patients who have suffered skeletal muscle trauma elevated blood levels are toxic to the kidneys. Prealbumin Prealbumin may also be known as transthyretin. It is a protein that is measured to assess nutritional status (note that it IS NOT a form of albumin it is called prealbumin because it runs faster than albumin on electrophoresis gels). While levels of other proteins can also point to nutritional status, prealbumin is probably the best indicator, because it breaks down quickly and therefore levels are indicative of any short term changes. It is often measured in hospitalised patients, where low levels point to poorer outcomes and longer hospital stays. RF (Rheumatoid Factor) RF is a protein whose levels are increased in patients with Rheumatoid Arthritis. The test is not wholly specific to RA, and levels may also be increased in other autoimmune conditions. RBP (Retinol Binding Protein) RBP is a protein that transports retinol (Vitamin A) from the liver to the tissues. Most RBP is bound to transthyretin (prealbumin), which prevents its loss through the kidneys. Excretion of RBP into the urine can indicate kidney damage. Serum levels are typically increased in Type 2 Diabetes, obesity and CVD. Transferrin Transferrin is an iron transport protein. It is measured to assess the body s ability to transport iron to tissues where it is needed. Most of the iron absorbed from food is transported to the bone marrow and used to make haemoglobin for red blood cell production. The remainder is stored as ferritin. Not all labs will run the Transferrin test some labs will run TIBC (a general chemistry assay) as an estimation of transferrin. 24

32 Therapeutic Drug Tests Therapeutic Drug Monitoring (or TDM) tests are run to ensure that a prescribed drug is present in a patient s system at the optimum concentration. Many TDM tests are run as immunological methods and depending on the hospital, the tests will be run either on the immunoassay analyser, or on the routine biochemistry analyser as IT methods. Other drug levels will be measured by classical clinical chemistry methods. Randox supplies a range of TDM assays, using IT and other clinical chemistry methods, along with a TDM control and RIQAS programme. For sites that run their TDM assays as immunoassays, the Randox Immunoassay controls contain a large number of drugs. Not all prescribed drugs require monitoring. Typically, the drugs that are measured are those where there is a narrow gap between the therapeutic and toxic concentrations. The below drugs are the main ones that are routinely monitored and the table indicates the sample type measured and where Randox has reagents, IQC sera and RIQAS programmes available. Note that many of these drugs will be present in multiple IQC materials / RIQAS programmes. Serum / plasma test Whole blood test Randox reagent available Randox IQC available RIQAS programme available DRUG CATEGORY DRUGS TREATMENT USE Cardiac drugs Digoxin Digitoxin Amiodarone Lidocane Quinidine Procainamide Antibiotics Gentamicin N-acetyl-procainamide (NAPA) Tobramycin Amikacin Vancomycin Chloramphenicol Congestive heart failure, angina, arrhythmias Infections with bacteria that are resistant to less toxic antibiotics 25

33 DRUG CATEGORY DRUGS TREATMENT USE Antiepileptics Bronchodilators Immunosuppressants 1. Phenobarbital 2. Phenytoin 3. Primidone 4. Valproic Acid 5. Carbamazepine 6. Ethosuximide Theophylline Caffeine Cyclosporine Everolimus Sirolimus (Rapamycin) Tacrolimus (FK506, Fugimycin) Epilepsy, prevention of seizures, sometimes to stabilise moods Asthma, chronic obstructive pulmonary disorder (COPD) To prevent rejection of transplanted organs Anti-cancer drugs Methotrexate Psoriasis, rheumatoid arthritis, various cancers Psychiatric drugs Lithium Some antidepressants o Imipramine o Amitriptyline o Nortriptyline o Desipramine Bipolar disorder (manic depression), depression Painkiller drugs Paracetamol (Acetaminophen) Salicylate (Aspirin) Reduction of pain and / or fever 26

34 Haematology Tests Haematology tests are run to give information on the cells circulating in a patient s blood. Randox does not supply haematology analysers or tests (machines are essentially cell counters, so reagents are not required). However, Randox does supply an internal control material for Sysmex analysers and a RIQAS programme that can be used with all machines. All of the below parameters (plus more) are available in the Randox IQC material. The below parameters, with the exception of the WBC differential, are available in the RIQAS programme. There are 3 main types of circulating blood cells: Red blood cells (erythrocytes) White blood cells (leukocytes) Platelets Abnormally high or low counts can signify many different types of disease, and blood counts are among the most common lab tests performed. The most common test is referred to as the Complete Blood Count (CBC) or Full Blood Count (FBC). The CBC generally includes: RBCs The number of red blood cells, given as an absolute number per litre. Haemoglobin Haemoglobin is the oxygen carrying pigment in the blood. Low levels signify anaemia. Levels are measured in g/l (this follows a recent recommendation to switch reporting units from g/dl, meaning that reported haemoglobin values are a factor of 10 higher than previously). Haematocrit (also known as Packed Cell Volume, PCV) This is the proportion of the blood that is occupied by red blood cells. Red Blood Cell Indices The total RBC count doesn t really provide any information on the quality of the cells, but the below 3 measurements can describe the red cell population: Mean Cell Volume (MCV) the average volume of the red cells. Dividing the haematocrit (the volume of the blood taken up by red cells) by the RBC count will give the MCV. Mean Cell Haemoglobin (MCH) the average amount of haemoglobin per red blood cell. Dividing the haemoglobin by the RBC count will provide this information. Mean Cell Haemoglobin Concentration (MCHC) the average concentration of haemoglobin in the cells. It is calculated using the haematocrit (total red cell volume of the blood) and the haemoglobin values. 27

35 Red Blood Cell Distribution Width (RDW) This is a comparison of the size of each RBC to the average RBC size. This indicates the variability in the sizes of the RBCs. Platelets Platelets are essential for blood clotting. Low platelet counts will lead to increased clotting times, while increased platelet counts may lead to unnecessary clotting. Mean Platelet Volume (MPV) This is a measurement of the average size of the platelets. High MPV is associated with a higher risk of stroke / heart attack. WBCs The number of white blood cells, given as an absolute number per litre. Increases in WBC count can often indicate infection. WBC Differential This may or may not be part of the CBC. This assessment reports the % of the different types of WBC present. Elevations of the different types of WBC are implicated in different types of viral, bacterial or parasitic infection, as well as malignancies and allergic reactions. Labs will measure either a 3-part or a 5-part differential, depending on the type of analyser they have. The 3-part differential machines tend to be smaller and more suited to small labs / PoC, while core labs will have 5-part differential machines. The 5-part differential reports the proportions of the following WBC sub-types: Neutrophils Lymphocytes Monocytes Eosinophils Basophils The 3-part differential assesses the WBC sub-types by size and reports: Lymphocytes (small) Monocytes (large) Granulocytes (medium) comprises Neutrophils, Eosinophils, Basophils 28

36 Coagulation Tests Coagulation tests measure the blood s ability to clot. When an injury occurs that results in bleeding, a process ensues that forms a clot over the injury, preventing further blood loss while the injury heals. When the injury has healed, the clot is broken down and removed. In healthy individuals, there is a balance between clot formation and clot removal. Clotting disorders involve conditions where the blood clots too readily, leading to increased risk of thrombosis and also, conditions where the blood clots too slowly, leading to increased risk of haemorrhage. These overall shortened / lengthened clotting times can be due to problems with many different proteins and factors that are involved in the various parts of the clotting process. The below lab tests are run to determine where in the clotting cascade a problem lies. The coagulation cascade involves extrinsic and intrinsic pathways, which merge into a common pathway, resulting in clot formation. Different factors / proteins are involved in each of these pathways, and the different tests help evaluate in which pathway a problem lies. Coagulation assays are typically run in a hospital s Haematology Laboratory. Randox supplies a basic range of coagulation assays for the RX Monza, but also supplies a comprehensive control material and a RIQAS programme containing many more parameters. The below table indicates the Randox product(s) associated with each parameter: Randox Monza assay available Randox IQC available RIQAS programme available 29