Ebook Wallach''s interpretation of diagnostic tests (10th edition): Part 2

SECTION 12

LAB TESTS


Chapter 16

Laboratory Tests
Lokinendi V. Rao and Liberto Pechet

1,5-Anhydroglucitol (1,5-AG)
11-Deoxycortisol
17α-Hydroxyprogesterone
17-Ketosteroids, Urine (17-KS)
5,10-Methylenetetrahydrofolate Reductase (MTHFR) Molecular Assay
5-Hydroxyindoleacetic Acid (5-HIAA) Urine
5′-Nucleotidase (5′-ribonucleotidephosphohydrolase, 5′-NT)
Acetaminophen (N-Acetyl-p- Aminophenol; APAP)
Acetylsalicylic Acid
Acid Phosphatase
ACTH Stimulation (Cosyntropin) Test
Activated Clotting Time (ACT)
Activated Protein C Resistance (APCR)
Adiponectin
Adrenocorticotropic Hormone (ACTH)
Allergen Tests, Specific Immunoglobulin E (IgE)
Albumin, Serum
Alcohols (Volatiles, Solvents)
Aldosterone
Alkaline Phosphatase (ALP)
Alpha1 -Antitrypsin (AAT, Alpha-1 Trypsin Inhibitor, Alpha-1 Proteinase Inhibitor)

α-Fetoprotein (AFP) Tumor Marker, Serum
Aminotransferases (AST, ALT)
Ammonia (Blood NH3 , NH3 , NH4 )
Amniocentesis
Amphetamines
Amylase
Amylase, Urine (Amylase/Creatinine Clearance Ratio [ALCR])
Androstenedione, Serum
Angiotensin II
Angiotensin-Converting Enzyme (ACE, Kinase II)
Anion Gap (AG)
Antiarrhythmic Drugs
Antibiotics
Anticardiolipin Antibodies (ACAs)
Anticoagulants, Circulating
Anticoagulation DNA Panel
Anticonvulsants


Antidepressants
Antidiuretic Hormone
Antihypertensives
Anti-inflammatories
Antineoplastics
Antimitochondrial Antibodies
Anti–Smooth Muscle Antibodies (ASM)
Anti-parietal Cell Antibodies (APC)
Antineutrophil Cytoplasmic Antibody (ANCA)
Antinuclear Antibody (ANA)
Antipsychotics

AntiSperm Autoantibodies– Immunobead Binding Test
Antithrombin (AT)
Apolipoproteins (Apo) A-1 and B
Benzodiazepines
Beta-2 Microglobulin, Serum, Urine, Cerebrospinal Fluid
Bicarbonate (HCO3− ), Blood
Bilirubin; Total, Direct, and Indirect
Bleeding Time (BT)
Blood Gas, pH
Blood Urea Nitrogen (BUN)
Bone Marrow Analysis
Brain Natriuretic Peptide (BNP)
Bronchodilators
β-Trace Protein
BUN-to-Creatinine Ratio
Calcitonin
Calcium, Ionized
Calcium, Total
Calcium, Urine
Calprotectin, Stool
Cancer Antigen 15-3 (CA 15-3)
Cancer Antigen 19-9 (CA 19-9)
Cancer Antigen 27.29 (CA 27.29)
Cancer Antigen-125 (CA-125), Serum
Cannabis Sativa
Carbon Dioxide, Total
Carboxyhemoglobin (Carbon Monoxide, COHB, HBCO)
Carcinoembryonic Antigen (CEA)
Cardiovascular Drugs (See Digoxin)
Catecholamines, Serum

Cell Count, Body Fluid Analysis
Cerebrospinal Fluid (CSF)
Other Body Fluids: Pleural, Pericardial, and Peritoneal Spaces
Ceruloplasmin
Chloride
Chloride, Urine
Cholesterol, High-Density Lipoprotein (HDL)
Cholesterol, Low-Density Lipoprotein (LDL)
Cholesterol, Total, Serum
Cholinesterase (Pseudocholinesterase) and Dibucaine Inhibition
Chorionic Villus Sampling
Chromogranin A, Plasma
Clot Retraction
Clotting Factors
Clotting Time (Lee-White Clotting Time)
Cobalt


Cocaine
Cold Agglutinins
Combined First-Trimester and Second- Trimester Screening (Integrated/ Sequential Screening)
Complement System Assays
Complete Blood Count (CBC)

Coombs (Antiglobulin) Test
Direct Coombs Test (DAT)
Indirect Coombs Test (IAT)
Co-oximetry
Copper
Corticotropin-Releasing Hormone (CRH)

Corticotropin-Releasing Hormone (CRH) Stimulation Test
Cortisol Free Urine, 24 Hours
Cortisol, Saliva
Cortisol, Serum
C-Peptide
C-Reactive Protein, High Sensitivity
C-Reactive Protein (Crp), Serum
Creatine
Creatine Kinase (CK), Total
Creatine Kinase Isoenzymes (CK-BB, CK-MM, CK-MB)
Macro CK Isoenzyme
Creatine Kinase MB (CK-MB)
Creatinine Clearance (CrCl)
Creatinine with Estimated Glomerular Filtration Rate (eGFR)
Creatinine, Urine
Cryofibrinogen
Cryoglobulins
Crystal Identification, Synovial Fluid
Cyclic Citrullinated Peptide Antibody, IgG
Cystatin C (CysC)
Cystic Fibrosis (CF) Mutation Assay
Cystine, Urine (Cystinuria Panel)
Cytogenetics: Fluorescence In Situ Hybridization (FISH), Chromosome Analysis, and Karyotyping
D-Dimers
Dehydroepiandrosterone Sulfate, Serum (DHEA-Sulfate)
Dehydroepiandrosterone, Serum (DHEA, DHEA Unconjugated)
Dexamethasone Suppression of Pituitary ACTH Secretion Test (DST)
Low-Dose Test: Overnight 1-mg Screening Test
Low-Dose Test: Standard 2-Day (2-mg) Test
High-Dose Test: Overnight (8-mg) Test

High-Dose Test: Standard 2-Day (8-mg) Test
Digoxin
Dilute Russell Viper Venom (dRVVT) Assay
Direct and Indirect Antiglobulin Tests (DAT and IAT)
Enzyme Tests That Detect Cholestasis (ALP, 5′-Nucleotidase, GGT, LAP)
Erythrocyte Sedimentation Rate (ESR)
Estradiol, Unconjugated
Estrogen/Progesterone Receptor Assay
Estrogens (Total), Serum
Estrone
Ethylene Glycol
Factor V Leiden Molecular Assay
Factor VIII (Antihemophilic Factor)
Factor XI
Factor XII (Hageman Factor)
Factor XIII


Fatty Acids, Free
Fecal Fat
Ferritin
Fetal Biopsy
Fetal Blood Sampling (Percutaneous Umbilical Blood Sampling [PUB], Cordocentesis)
Fetal Lung Maturity (FLM)— Lamellar Body Counts (LBC)
Fibrinogen (Factor I)
Fibrinogen Degradation Products (FDPs)
Fibronectin, Fetal (fFN)
First-Trimester Screening
Flow Cytometry Analysis in the Clinical Evaluation of Hematologic Diseases
Folate, Serum and Erythrocytes (RBCs)

Follicular-Stimulating Hormone (FSH) and Luteinizing Hormone (LH), Serum
Fructosamine, Serum
Galactose-1-Phosphate Uridyltransferase (GALT)
Gamma Glutamyl Transferase (GGT)
Gastrin
Gaucher Disease Molecular DNA Assay
Genetic Carrier Testing
Ghrelin
Gliadin (Deamidated) Antibodies, IgG and IgA
Glucagon
Glucagon Stimulation Test
Glucose Tolerance Test, Oral (OGTT)
Glucose, Cerebrospinal Fluid (CSF)
Glucose, Urine
Glucose, Whole Blood, Serum, Plasma
Glucose-6-Phosphate Dehydrogenase (G6PD)
Growth Hormone (GH)
Growth Hormone–Releasing Hormone (GHRH, Somatocrinin)
Hallucinogens
Haptoglobin
Heavy Metals
Hematocrit (Hct)
Hemoglobin (Hb)
Hemoglobin (Hb) Variant Analysis
Hemoglobin A1c
Heparin Anti-Xa (Low Molecular Weight Heparin)
Heparin-Induced Thrombocytopenia (HIT) Assays
Hereditary Hemochromatosis Mutation Assay
High Molecular Weight Kininogen and Prekallikrein (Fletcher Factor)
Homocysteine (Hcy)

Homovanillic Acid, Urine (HVA)
Human Chorionic Gonadotropin (hCG)
Human Leukocyte Antigen (HLA) Testing
HLA Testing and Disease Associations/Drug Hypersensitivity Reactions
HLA and Stem Cell Transplant
Hydroxybutyrate Beta (BHB)
Immunoglobulin A (IgA)
Immunoglobulin D (IgD)
Immunoglobulin E (IgE)
Immunoglobulin G (IgG)
IgG-to-Albumin Ratio, CSF
Immunoglobulin M (IgM)
Immunoglobulins, Free Light Chains, Serum
Immunosuppressants
Inhibins A and B, Serum


Insulin
Insulin Tolerance Test
Insulin-Like Growth Factor–Binding Protein-3 (IGFBP-3)
Insulin-Like Growth Factor-I (IGF-I)
Insulin-Like Growth Factor-II
Insulin–to–C-Peptide Ratio
Intrinsic Factor Antibody
Iodine Excretion, Urine
Hours
Iron (Fe)
Iron-Binding Capacity, Total (TIBC)
Iron Saturation
Islet Autoantibodies (IAA)

Janus Kinase-2 (JAK2) DNA Mutation Assay
Kleihauer-Betke Test
Lactate Dehydrogenase
Lactate Dehydrogenase Isoenzymes
Lactate, Blood
Lactoferrin, Stool
Lead (Pb)
Lecithin-to-Sphingomyelin (L:S) Ratio
Leptin
Leucine Aminopeptidase
Leukocyte Alkaline Phosphatase (LAP)
Lipase
Lipoprotein-Associated Phospholipase A2 (Lp-PLA2 ) 1034 Lupus Anticoagulant (LA)
Luteinizing Hormone (LH)
Magnesium (Mg)
Magnesium, Urine
Maternal Screening
Mean Corpuscular Hemoglobin (MCH)
Mean Corpuscular Hemoglobin Concentration (MCHC)
Mean Corpuscular Volume (MCV)
Mean Platelet Volume (MPV)
Metanephrines, Urine
Methotrexate
Methylmalonic Acid
Metyrapone Test
Microalbumin, Urine
Müllerian Inhibiting Substance
Multigene Carrier Panels
Myeloperoxidase (MPO), Plasma
Myoglobin

Neuron-Specific Enolase (NSE)
Neutrophil Tests for Dysfunction
Nicotine/Cotinine
Noninvasive Prenatal Testing (NIPT)
Occult Blood, Stool
Opiates
Opioids
Osmolal Gap
Osmolality, Serum and Urine
Osmolality, Stool
Parathyroid Hormone (PTH)
Parathyroid Hormone–Related Peptide (PTHrP)
Partial Pressure of Carbon Dioxide (pCO2 ), Blood
Partial Pressure of Oxygen (pO2 ), Blood


Partial Thromboplastin Time (PTT, aPTT)
Peripheral Blood Smears (PBS)
Phosphate, Blood
Phosphatidylglycerol (PG)
Phospholipids
Phosphate, Urine
Plasma Renin Activity (PRA)
Plasminogen
Plasminogen Activator Inhibitor 1 (PAI 1)
Platelet Aggregation
Platelet Antibody Detection
Platelet Count
Platelet Function Assay, In Vitro
Pleura, Needle Biopsy (Closed Chest)

Potassium (K)
Potassium, Urine
Prealbumin

Prenatal Testing: Sample Collection Procedures
Amniocentesis
Chorionic Villus Sampling
Fetal Biopsy
Fetal Blood Sampling (Percutaneous Umbilical Blood Sampling [Pubs], Cordocentesis)

Prenatal Screening
Prenatal Screening, First-Trimester Screening
Noninvasive Prenatal Testing (NIPT)
Prenatal Screening, Second-Trimester Screening (Maternal Serum Screening; Quad Screen)
Combined First-Trimester and Second- Trimester Screening (Integrated/ Sequential Screening)

Prenatal Diagnostic Screening
Cytogenetics: Fluorescence In Situ Hybridization (FISH), and Chromosome Analysis
Genomic Microarray Analysis— Array Comparative Genomic Hybridization (aCGH)
Molecular Genetic Analysis (Prenatal DNA Analysis)
Pretransfusion Compatibility Testing
Procalcitonin (PCT)
Progesterone
Proinsulin
Prolactin
Prostate-Specific Antigen (PSA), Total and Free
Protein (Total), Serum
Protein (Total), Urine
Protein C
Protein S

Protein, Cerebrospinal Fluid
Prothrombin G20210A Molecular Mutation Assay
Prothrombin Time (PT) and the International Normalized Ratio (INR)
Pyruvate Kinase (PK), Red Blood Cell
Quantitative Pilocarpine Iontophoresis Sweat Test
Red Blood Cells (RBCs): Count and Morphology
Red Cell Distribution Width (RDW)
Reptilase Time (RT)
Reticulocytes
Reverse T3 (rT3 ), Triiodothyronine, Reverse
Rheumatoid Factor (RF)
Rosette Test
Salicylates (Aspirin)
Screening for Fetal Chromosome Abnormalities and Neural Tube Defects


Second-Trimester Screening (Maternal Serum Screening; Quad Screen)
Sedative–Hypnotics
Barbiturates
Semen Analysis
Semen Fructose
Serotonin, Blood
Serum Protein Electrophoresis/ Immunofixation
Sex Hormone–Binding Globulin (SHBG)
Sickle Solubility Test (SST)
Sodium (Na)
Sodium, Urine
Tay-Sachs Disease Molecular DNA Assay
Testosterone, Total, Free, Bioavailable
Theophylline (1,3-Dimethylxanthine)

Thrombin Time (TT)
Thromboelastogram (TEG)
Thyroglobulin (Tg)
Thyroid Autoantibody Tests
Thyroid Hormone–Binding Ratio (THBR)
Thyroid Radioactive Iodine Uptake (RAIU)
Thyroid-Stimulating Hormone (TSH)
Thyrotropin-Releasing Hormone (TRH) Stimulation Test
Thyroxine, Free (FT4 ) 1159 Thyroxine, Total (T4 ) 1160 Thyroxine-Binding Globulin (TBG)
Tissue Transglutaminase IgA Antibody (tTG-IgA)
Transferrin (TRF)
Triglycerides
Triiodothyronine (T3 ) 1168 Triiodothyronine (T3 ) Resin Uptake (RUR)
Troponins, Cardiac-Specific Troponin I and Troponin T
Urea Nitrogen, Urine
Uric Acid (2,6,8-Trioxypurine, Urate)
Uric Acid, Urine
Urinalysis, Complete
Urine Protein Electrophoresis/ Immunofixation
Urovysion™ FISH for Bladder Cancer
Vanillylmandelic Acid (VMA), Urine
Vasoactive Intestinal Polypeptide (VIP)
Viscosity, Serum
Vitamin A (Retinol, Carotene)
Vitamin A Relative Dose–Response (RDR) Test
Vitamin B1 (Thiamine)
Vitamin B12 (Cyanocobalamin, Cobalamin)
Vitamin B2 (Riboflavin)
Vitamin B6 (Pyridoxine)
Vitamin C (Ascorbic acid)

Vitamin D, 1,25-Dihydroxy
Vitamin D, 25 Hydroxy
Vitamin E (Alpha-Tocopherol)
von Willebrand Disease (VWD) Assays
Results
Water Deprivation Test
White Blood Cell: Inclusions and Morphologic Abnormalities
White Blood Cell Counts and Differentials
Xylose Absorption Test
Zinc (Zn)


This Chapter presents the most commonly ordered serum, plasma, and whole blood laboratory tests
arranged in alphabetical order. Each entry is titled using the most common naming convention existing
in the United States. When appropriate, alternate name(s), definition, reference ranges, clinical use,
interpretation, limitations, and suggested readings are given. Microbiology tests such as laboratory
cultures have been organized into a separate Chapter, Infectious Disease Assays (p. 1203). The basis
of current molecular assays is reviewed in the Chapter on Hereditary and Genetic Diseases (p. 473).
It is important to note that many of these tests are available by point-of-care testing (POCT). The
main advantage of POCT is immediate turnaround time. However, it is also necessary to consider the
disadvantages of POCT, such as reliability of interpretation due to lower assay sensitivity and
susceptibility to interfering substances. Other issues include ensuring personnel proficiency, quality
assurance, data management, and cost.

1,5-ANHYDROGLUCITOL (1,5-AG)
Definition
1,5-Anhydroglucitol (1,5-AG), sometimes known as GlycoMark, is a monosaccharide that
shows a structural similarity to glucose. Its main source in humans is dietary ingestion,
particularly meats and cereals. In addition, 10% of 1,5-AG is derived from endogenous
synthesis. It is generally not metabolized, and in healthy subjects, it achieves a stable

plasma concentration that reflects a steady balance between ingestion and urinary excretion.
Normal range: 10.7–32.0 μg/mL in males; 6.8–29.3 μg/mL in females.

Use
Used clinically to monitor short-term glycemic control in patients with diabetes (1–2 weeks)
Useful marker for postprandial hyperglycemia
Performs better than hemoglobin A1C for monitoring glucose profile in pregnancies
complicated by type 1 diabetes

Interpretation
Increased In
1,5-AG may be increased during IV hyperalimentation.

Decreased In
Individuals with renal glucose thresholds that are markedly different from 180 mg/dL (e.g.,
chronic renal failure, pregnancy, and dialysis) and in those undergoing steroid therapy.
α-Glucosidase inhibitors can decrease 1,5-AG by interfering with its intestinal absorption.

Limitations
In patients with poorly controlled DM, 1,5-AG is less sensitive to modest changes in
glycemic control because of continuous glycosuria.
Levels can be influenced by factors such as dairy product, races, uric acid, triglycerides,


liver disease, gastrectomy state, and cystic fibrosis.

11-DEOXYCORTISOL
Definition
11-Deoxycortisol, also known as cortodoxone, corticosterone, and compound S, is a steroid
and an immediate precursor to the production of cortisol. It can be synthesized from 17hydroxyprogesterone. Excretion in urine is included in 17-ketogenic steroid (17-KGS) and

Porter-Silber 17-OHKS measurements, which were originally used to provide some
measure of cortisol production. The direct measurement of cortisol has replaced
determinations of 17-KS and 17-OHKS.
Normal range: <50 ng/dL in males; <33 ng/dL in females.

Use
Diagnosis of and monitoring therapeutic response in CAH due to 11β-hydroxylase
deficiency
Assessment of adrenal response in the metyrapone test; result after metyrapone stimulation is
>8,000 ng/dL

Interpretation
Increased In
Values are increased in CAH (P450cII deficiency) and following metyrapone administration
in normal persons.

Decreased In
Values are decreased in adrenal insufficiency.

Limitations
Patients with myxedema, some pregnant patients, and those on oral contraceptives respond
poorly during the test.

17α-HYDROXYPROGESTERONE
Definition
17α-Hydroxyprogesterone, also known as hydroxyprogesterone, is a 21-carbon steroid
produced in the adrenals—and also in the ovaries, testes, and placenta—that serves as a
biosynthetic precursor to cortisol.
Normal range: 18–469 ng/dL (see Table 16.1).
TABLE 16–1. Range of Normal Values for 17a-Hydroxyprogesterone

Use
Diagnosis and management of congenital adrenal hyperplasia, hirsutism, and infertility

Interpretation
Increased In
The luteal phase of menstruating women and pregnancy, during which it rises.
When defective 21-alpha hydroxylase and 11-beta hydroxylase are present.
The most common form of CAH, where deficiency of the enzyme 21-hydroxylase blocks
normal synthesis of cortisol, leading to a compensatory increase of ACTH secretion; this
results in increased levels.

Limitations
Circulating normally exhibits a diurnal pattern similar to that of cortisol, with higher values
in the early morning than in the late afternoon. Hence, the time of collection should be
standardized.
Spuriously elevated levels are sometimes seen in premature and sick newborns due to
interference with other steroid metabolites. 17α-Hydroxypregnenolone sulfate (percent
cross-reactivity: 3.8%) has been identified as the most significant interferent in direct
assays.
17α-Hydroxyprogesterone values for women with late-onset CAH have been found to
overlap with those encountered in hirsute, oligomenorrheic women who do not have the
disorder. Accordingly, it is important to determine ACTH-stimulated 17αhydroxyprogesterone levels in women suspected of having late-onset CAH.

17-KETOSTEROIDS, URINE (17-KS)
Definition
17-Ketosteroids, urine (17-KS), are breakdown products of androgens and are an adrenal
function test. Examples of 17-KS include androstenedione, androsterone, estrone, and
dehydroepiandrosterone. An alternative and more specific test for adrenal androgen

function is dehydroepiandrosterone sulfate in serum.
Normal range: depends on sex and age (Table 16.2).


TABLE 16–2. Normal Ranges for 17-Ketosteroids in the Urine

Use
Evaluation of glucocorticoid production and neuroendocrine function
Evaluation of androgenic adrenal and testicular function in normal male individuals and
primarily adrenal androgenic secretion in normal female individuals

Interpretation
Increased In
Adrenal tumor
Congenital adrenal hyperplasia (very rare)
Cushing syndrome
Ovarian cancer
Testicular cancer
Ovarian dysfunction (polycystic ovarian disease)

Decreased In
Addison disease
Castration
Hypopituitarism
Myxedema
Nephrosis

Limitations
A large number of substances may interfere with this test.
Decreases may be caused by carbamazepine, cephaloridine, cephalothin, chlormerodrin,

digoxin, glucose, metyrapone, promazine, propoxyphene, reserpine, and others.


Increases may be caused by acetone, acetophenide, ascorbic acid, chloramphenicol,
chlorothiazide, chlorpromazine, cloxacillin, dexamethasone, erythromycin, ethinamate,
etryptamine, methicillin, methyprylon, morphine, oleandomycin, oxacillin, penicillin,
phenaglycodol, phenazopyridine, phenothiazine, piperidine, quinidine, secobarbital,
spironolactone, and others.

5,10-METHYLENETETRAHYDROFOLATE REDUCTASE (MTHFR)
MOLECULAR ASSAY*
Definition
Mutations, C677T and A1298C, in the 5,10-methylenetetrahydrofolate reductase (MTHFR)
gene increase the risk of thrombosis (OMIM# 188050) and other cardiovascular disorders
as a result of an elevated plasma homocysteine concentration (OMIM# 236250).
Normal values: negative or no mutations are found.

Use
Suspected coronary artery disease, homocystinuria, neural tube defects, spontaneous
abortion, or MTHFR deficiency

Limitations
The results of a genetic test may be affected by DNA rearrangements, blood transfusion,
bone marrow transplantation, or rare sequence variations.

5-HYDROXYINDOLEACETIC ACID (5-HIAA) URINE
Definition
5-Hydroxyindoleacetic acid (5-HIAA), also known as serotonin metabolite, is the major
urinary metabolite of serotonin.
Normal range: 0.0–15.0 mg/day (24-hour urine); 0.0–14.0 mg/g creatinine.

Use
Helps diagnose and monitor treatment for serotonin-secreting carcinoid tumors

Interpretation
Increased In
Whipple disease
Nontropical sprue
Small increases possible in pregnancy, ovulation, and postsurgical stress
Various food ingestions (e.g., pineapples, kiwi, bananas, eggplant, plums, tomatoes,
avocados, plantains, walnuts, pecans, hickory nuts, coffee)


Use of certain drugs (e.g., acetanilid, acetaminophen, acetophenetidin, caffeine, coumaric
acid, diazepam [Valium], ephedrine, fluorouracil, glyceryl guaiacolate [guaifenesin],
heparin, melphalan [Alkeran], mephenesin, methamphetamine, methocarbamol, naproxen,
nicotine, Lugol solution, promethazine, phenothiazine, hydroxyl tryptophan)

Decreased In
Use of certain drugs (e.g., chlorpromazine, promazine, imipramine, isoniazid, monoamine
oxidase inhibitors, methenamine, methyldopa, phenothiazines, promethazine)
Renal insufficiency (possible)

Limitations
Foods rich in serotonin and medications, over-the-counter drugs, and herbal remedies that
may affect metabolism of serotonin must be avoided at least 72 hours before and during
collection of urine for 5-HIAA.
Twenty-four–hour collections are generally recommended, but random collections may be
used. Refrigeration is the most important aspect of specimen preservation.
Urinary 5-HIAA is increased with malabsorption, in 75% of cases, usually when a carcinoid

tumor is far advanced (with large liver metastases, often 300–1,000 mg/day), but may not be
increased despite massive metastases.
Sensitivity is 73%.
The test is useful in the diagnosis of only 5–7% of patients with carcinoid tumors but in
approximately 45% of those with liver metastases.
Disease extent and prognosis correlate generally with urine 5-HIAA excretion, and the level
becomes normal after successful surgery. If urine HIAA is normal, the blood level of
serotonin or a precursor, 5-hydroxytryptophan should be checked.

5′-NUCLEOTIDASE (5¢-RIBONUCLEOTIDEPHOSPHOHYDROLASE, 5′NT)
Definition
This membrane-bound enzyme of the liver is increased in diseases of the liver, particularly
if the hepatobiliary tract is involved. The appearance of 5′-NT in serum is due to
cholestasis, and its significance is similar to that of ALP and GGT. However, 5′-NT is not
as subject to drug induction as GGT and ALP, and it is not subject to confusion with
alternate sources of the enzyme, as is seen with ALP.
Normal range: 2.0–8.0 U/L.

Use
Determining cholestatic liver disease, particularly when GGT and ALP could be falsely
elevated due to drug induction
Better test for secondary tumors and lymphomas of the liver than ALP


Interpretation
Increased In
5′-NT is increased in the following conditions:
Hepatobiliary disease with intrahepatic or extrahepatic biliary obstruction
Hepatic carcinoma
Early biliary cirrhosis

Pregnancy (third semester)
Inflammatory arthritis

Limitations
5′-NT can be elevated in hyperammonemia due to analytical interference.
Normal in pregnancy and postpartum period (in contrast to serum leucine aminopeptidase
and ALP).

ACETAMINOPHEN (N-ACETYL-p-AMINOPHENOL; APAP)
Definition
Nonopioid analgesic, antipyretic

Use
Relief of pain, such as headaches and toothaches
Reduction of fever

Interpretation
Screen of urine: indication of exposure
Screen of serum: used to assess potential toxicity
Normal range: 5–20 μg/mL serum
Potentially toxic: >150 μg/mL measured 4 hours postdose

Limitations
Screening
Serum/urine: colorimetric or immunoassay on automated chemistry analyzers
High bilirubin concentrations [>50 μg/mL] may cause false-positive results with
immunoassay-based tests.
Plasma may be tested in place of serum. Anticoagulants such as EDTA and heparin
do not generally interfere with the assay.
Do not use whole blood.

Confirmation:
Serum/urine–HPLC or GC/MC


APAP is highly conjugated by glucuronidation and sulfation.
An assay that includes a hydrolysis step provides total APAP levels, which are not
useful for assessing toxicity.

ACETYLSALICYLIC ACID
See Salicylates (Aspirin).

ACID PHOSPHATASE
Definition
Acid phosphatase is a hydrolytic enzyme secreted by various cells, and it has five
isoenzymes. The greatest amount per gram of tissue is found in semen (prostate); it is also
detectable in bone, liver, spleen, kidney, RBCs, and platelets. The acid phosphatase test is
also known as prostatic acid phosphatase (PAP), the serum acid phosphatase test, and the
tartrate-resistant acid phosphatase (TRAP) test.
Normal range: 0–0.8 U/L.

Use
Predicts recurrence after radical prostatectomy for clinically localized prostate cancer and
following response to androgen ablation therapy, when used in conjunction with PSA

Interpretation
Increased In
Acid phosphatase is increased in the following conditions:
Prostate cancer
Gaucher disease and Niemann-Pick disease
One day to 2 days after prostatic surgery or biopsy

Prostatic manipulation or catheterization
Benign prostatic hyperplasia, prostatitis, prostate infarct
Vaginal swabs from rape victims.

Limitations
PAP is no longer used to screen for or to stage prostate cancer. In most instances, serum PSA
is used instead.
PAP measurement must not be regarded as an absolute test for malignancy, since other
factors including benign prostatic hyperplasia, prostatic infarction, and manipulation of the
prostate gland may result in elevated serum PAP concentrations.
PAP measurements provide little additional information beyond that provided by PSA
measurements.


Suggested Reading
Moul JW, Connelly RR, Perahia B, et al. The contemporary value of pretreatment prostatic acid phosphatase to predict pathological stage
and recurrence in radical prostatectomy cases. J Urol. 1998;159:935–940.

ACTH STIMULATION (COSYNTROPIN) TEST
Definition
Cosyntropin is synthetic ACTH (1–24), which has the full biologic potency of native ACTH
(1–39). It is a rapid stimulator of cortisol and aldosterone secretion.

Use
This is the initial test used to distinguish primary from secondary adrenal insufficiency.
It is not helpful in the diagnosis of Cushing syndrome. Several protocols are used to assess
the response to exogenous ACTH administration (see below).

Low-Dose ACTH Stimulation Test
This test involves physiologic plasma concentrations of ACTH and provides a more

sensitive index of adrenocortical responsiveness.
It is performed by measuring serum cortisol immediately before and 30 minutes after IV
injection of cosyntropin in a dose of either 1 μg/1.73 m2 or 0.5 μg/1.73 m2.
There is no commercially available preparation of “low-dose” cosyntropin. The vials of
cosyntropin currently available contain 250 μg and come with sterile normal saline to be
used as a diluent. One prepares the low-dose solution of cosyntropin locally.

High-Dose ACTH Stimulation Test
This test consists of measuring serum cortisol immediately before and 30 and 60 minutes
after IV injection of 250 μg of cosyntropin. This dose of cosyntropin results in
pharmacologic plasma ACTH concentrations for the 60-minute duration of the test.
The advantage of the high-dose test is that the cosyntropin can be injected using the IM route,
because pharmacologic plasma ACTH concentrations are still achieved.
Salivary cortisol can also be measured during this test. Salivary cortisol increases to 19 ±
0.8 ng/mL (range: 8.7–36 ng/mL) 1 hour after injection.

Eight-Hour ACTH Stimulation Test
The 8-hour test, which is now rarely performed, consists of infusing 250 μg of cosyntropin
continuously over 8 hours in 500 mL of isotonic saline. A 24-hour urine specimen is
collected the day before and the day of the infusion for cortisol or 17-hydroxycorticoid and
creatinine determination, and serum cortisol is determined at the end of the infusion. Plasma
ACTH concentrations are supraphysiologic throughout the infusion.
The 24-hour urinary excretion of 17-hydroxycorticoid should increase three-to fivefold over
baseline on the day of ACTH infusion.

Two-Day ACTH Infusion Test


The 2-day ACTH infusion test is similar to the 8-hour infusion test, except that the same
dose of ACTH is infused for 8 hours on 2 consecutive days.

This test may be helpful in distinguishing secondary from tertiary adrenal insufficiency. The
1-day 8-hour test is too short for this purpose, whereas longer tests add little further useful
information.
Urinary excretion of 17-hydroxycorticoid should exceed 27 mg during the first 24 hours of
infusion and 47 mg during the second 48 hours.

Interpretation
Low-dose stimulation test: A value of 18 μg/dL or more, before or after ACTH injection, is
indicative of normal adrenal function.
High-dose stimulation test: A serum cortisol value of 20 μg/dL or more at any time during
the test, including before injection, is indicative of normal adrenal function.
Eight-hour stimulation test: Serum cortisol should reach 20 μg/dL in 30–60 minutes after the
infusion is begun and exceed 25 μg/mL after 6–8 hours.
Two-day infusion test: Serum cortisol should reach 20 μg/mL in 30–60 minutes after the
ACTH infusion is begun and exceed 25 μg/mL after 6–8 hours. Both serum and urinary
steroid values increase progressively thereafter, but the ranges of normal are not well
defined.

Limitations
In healthy individuals, cortisol responses are greatest in the morning, but in patients with
adrenal insufficiency, the response to cosyntropin is the same in the morning and afternoon.
Therefore, ACTH stimulation tests should be done in the morning to minimize the risk of
misdiagnosis in a normal individual.
The criteria for a minimal normal cortisol response of 18–20 μg/dL are derived from the
responses of healthy volunteers. However, in some studies, higher cutoff points for the
diagnosis of adrenal insufficiency are based on the ACTH test responses of patients known
to have an abnormal response to insulin.
Variability in cortisol assays creates an additional problem with setting criteria for a normal
response to ACTH that apply to all centers. Studies comparing cortisol results obtained
with different assays showed a positive bias of Radioimmunoassays (RIA) and EIAs of 10–

50% compared to a reference value obtained using isotope dilution GC/MS.
In women, the response to ACTH is affected by the use of oral contraceptives, which
increase cortisol-binding globulin levels.
The response to ACTH varies with the underlying disorder. If the patient has
hypopituitarism with deficient ACTH secretion and secondary adrenal insufficiency, then
the intrinsically normal adrenal gland should respond to maximally stimulating
concentrations of exogenous ACTH if given for a sufficiently long time. The response may
be less than that in normal subjects and initially sluggish due to adrenal atrophy resulting
from chronically low stimulation by endogenous ACTH. If, on the other hand, the patient has
primary adrenal insufficiency, endogenous ACTH secretion is already elevated, and there
should be little or no adrenal response to exogenous ACTH.


A clearly subnormal response to the low-dose or high-dose ACTH stimulation test is
diagnostic of primary or secondary adrenal insufficiency, whereas a normal response
excludes both disorders.
Cortisol values between 18.0 and 25.4 μg/dL represent a range of uncertainty in which
patients may have discordant responses to ACTH, insulin, and/or metyrapone. Higher
concentrations represent a normal response in the non-ICU setting.
The low-dose test is not valid if there has been recent pituitary injury, and it supports the
conclusion that a 30-minute serum cortisol concentration <18 μg/dL indicates impaired
adrenocortical reserve. In addition, the low-dose test does not reliably indicate
hypothalamic–pituitary–adrenal axis suppression in preterm infants whose mothers received
dexamethasone for <2 weeks before delivery to hasten fetal lung development. The CRH
test should be used in this situation.

ACTIVATED CLOTTING TIME (ACT)*
Definition
Activated clotting time (ACT) is a rapid point-of-care standardized clotting time, performed
by automated well-calibrated instruments, such as the Medtronic automated coagulation

timer (ACT). A baseline ACT has to be established in each POCT area after induction of
anesthesia and opening the chest for cardiopulmonary bypass surgery, because surgery and
anesthesia shorten it. The ACT may also vary slightly with the lot number of the control
cartridge.
Normal range in the absence of heparin (with Medtronic coagulometer): 74–125
seconds.

Use
ACT is the most widely used measure of anticoagulation with heparin (and neutralization of
heparin with protamine) during extracorporeal circulation. After the initial dose of heparin,
the ACT is maintained at >275 seconds for off-pump coronary procedures and >350
seconds for on-pump procedures by periodic administration of heparin.

Interpretation
There is some controversy concerning whether monitoring heparinization by ACT alone
ensures optimal heparin and protamine doses. A poor correlation was found between ACT
and heparin measurements using anti-Xa assays. Nevertheless, experience has shown that
institution of anticoagulation and monitoring under ACT guidance and reversal improves
hemostasis, limits blood loss, and reduces the need for transfusions.

Limitations
The response of ACT to heparin varies from individual to individual and with heparin
potency.
Underlying coagulopathies (antithrombin III deficiency, clotting factor deficiencies, DIC)


must be excluded.
Medications that inhibit platelet function (aspirin, NSAIDs) may affect ACT.
Preanalytical errors (sample dilution or contamination with heparin, blood activation) must
be avoided. It is particularly important to avoid the use of blood samples contaminated by

heparin flushes.

ACTIVATED PROTEIN C RESISTANCE (APCR)*
Definition
APCR reflects resistance to proteolysis of activated factor V by activated protein C (APC).
Ninety-five percent of APCR cases are due to factor V Leiden, a genetic mutation in factor
V that predisposes to venous thromboembolism (5–10 times greater risk in heterozygotes
and 50–100 times greater risk in homozygote carriers). The remaining 5% are found in
pregnancy, malignancy, and the antiphospholipid antibody syndrome. Ratios are generated
either from a modified PTT or, more recently, by activating protein C with southern
copperhead venom, using dilute Russell viper venom as the clotting reagent. The test is
performed in the presence of added APC, where in normal individuals, there is an
elongation due to delayed generation of fibrin when factor V is lysed; in the absence of
APC, where factor V remains intact, there is no elongation. Patients with APCR have a
lesser prolongation of clotting in the presence of APC than controls.
Normal value: >1.8.

Use
APCR is one of the assays recommended to investigate the etiology of venous
thrombophilia. The congenital form, factor V Leiden, is present in 5% of individuals of
European descent and in a high proportion of patients with unprovoked venous
thromboembolism. It is virtually absent in patients of pure African ancestry.

Limitations
Protein C levels <50% and initial anticoagulation with vitamin K antagonists may give
falsely low ratios. In these situations, the genetic test for factor V Leiden is recommended.
The APCR assay is valid in patients stabilized on vitamin K antagonists or heparin.
The assay is invalid in clotted specimens, as well as in lipemic, hemolyzed, or icteric
samples. The assay is also invalid if blood is drawn with the wrong anticoagulant or the
tubes are not filled appropriately.

ADIPONECTIN
Definition
Adiponectin, a hormone secreted exclusively by adipose tissue, has an important role in the
regulation of tissue inflammation and insulin sensitivity. Perturbations in adiponectin
concentration have been associated with obesity and the metabolic syndrome. Levels of the


hormone are inversely correlated with body fat percentage in adults, whereas the
association in infants and young children is more unclear.
Normal range: see Table 16.3.
TABLE 16–3. Normal Range of Adiponectin

Use
Higher adiponectin levels are associated with a lower risk of type 2 diabetes across diverse
populations, consistent with a dose–response relationship.

Interpretation
Increased In
Twofold before a meal and decreases to trough levels within 1 hour after eating
More than twofold in hemodialysis patients

Decreased In
Type 2 diabetes mellitus
Obesity and metabolic syndrome

Limitations
Adiponectin exerts some of its weight reduction effects via the brain. This is similar to the
action of leptin, but the two hormones perform complementary actions and can have
additive effects.

Due to its important cardiometabolic actions, adiponectin represents a biologic molecule
worth being studied as a new emerging biomarker of disease and also as a target for
pharmacologic treatments.

Suggested Reading
Li S, Shin HJ, Ding EL, et al. Adiponectin levels and risk of type 2 diabetes: a systematic review and meta-analysis. JAMA.
2009;302(2):179–188.

ADRENOCORTICOTROPIC HORMONE (ACTH)
Definition
ACTH is a polypeptide hormone produced by the anterior pituitary gland that exists
principally as a chain of 39 amino acids, with a molecular mass of approximately 4,500 Da.
Its biologic function is to stimulate cortisol secretion by the adrenal cortex. ACTH secretion


is in turn controlled by the hypothalamic hormone CRF and by negative feedback from
cortisol.
Normal range: <46 pg/mL.

Use
Diagnosis of Addison disease, CAH, Cushing syndrome, adrenal carcinoma, and ectopic
ACTH syndrome

Interpretation
Increased In
Addison disease
CAH
Pituitary-dependent Cushing disease
Ectopic ACTH–producing tumors
Nelson syndrome

Decreased In
Secondary adrenocortical insufficiency
Adrenal carcinoma
Adenoma
Hypopituitarism

Limitations
Plasma levels of ACTH exhibit a significant diurnal variation. ACTH is normally highest in
the early morning (6–8 AM) and lowest in the evening (6–11 PM). Cortisol levels are
frequently measured at the same time as ACTH.
Because ACTH is released in bursts, its levels in the blood can vary from minute to minute.
ACTH is unstable in blood, and proper handling of specimen is important.
Most commercial RIAs are insensitive and nonspecific, measuring intact ACTH as well as
precursors and fragments. Highly sensitive IRMAs measure intact ACTH only.
RIAs are recommended for investigating ectopic ACTH–producing tumors, because some of
the tumors secrete ACTH precursors and fragments. IRMAs are more sensitive than RIAs
and are useful for investigating disorders of the hypothalamic–pituitary–adrenal system.
Patients taking glucocorticoids may have suppressed levels of ACTH with an apparent high
level of cortisol.
Pregnancy, menstruation, and stress increase secretion.

ALLERGEN TESTS, SPECIFIC IMMUNOGLOBULIN E (IgE)
Definition


Allergic diseases are manifested as hyperresponsiveness in the target organ, whether the
skin, nose, lung, or GI tract. Most tests for “allergy” are actually tests for allergic
sensitization, or the presence of allergen-specific IgE.
Most patients who experience symptoms upon exposure to an allergen have demonstrable

IgE that specifically recognizes that allergen, making these tests essential tools in the
diagnosis of allergic disorders.
In vitro testing for allergy has certain advantages:
It poses no risk to the patient of an allergic reaction.
It is not affected by medications (antihistamines, etc.) the patient may be taking.
It is not reliant upon skin integrity or affected by skin disease.
It can be more convenient for the patient. In vitro testing requires submitting a blood
sample and does not necessitate a separate visit for skin testing.
Clinical performance of specific IgE-based serum allergen tests typically has sensitivity
ranging from 84% to 95% and specificity ranging from 85% to 94%.
Various types of specific panels, mixes, as well as specific allergen tests currently
performed at various labs and contact your lab for details.
Normal range:

Use
To establish the diagnosis of an allergic disease and to define the allergens responsible for
eliciting signs and symptoms
To identify allergens that may be responsible for allergic disease and/or anaphylactic
episode and to confirm sensitization to particular allergens prior to beginning
immunotherapy
To investigate the specificity of allergic reactions to insect venom allergens, drugs, or
chemical allergens

Interpretation
Increased In
Detection of IgE antibodies in serum (Class 1 or greater) indicates an increased likelihood
of allergic disease as opposed to other etiologies and defines the allergens that may be
responsible for eliciting signs and symptoms.

Decreased In

NA.

Limitations
The demonstration of sensitization is not sufficient to diagnose an allergy, however, because
a sensitized individual may be entirely asymptomatic upon exposure to the allergen in
question. Thus, allergy tests must be interpreted in the context of the patient’s specific
clinical history, and the diagnosis of an allergic disorder cannot be based solely on a
laboratory result.
If the result is markedly positive (e.g., a Class VI result), the history suggests a past reaction
to the allergen, and the allergen is well characterized, then the diagnosis of an allergy can
usually be made without further evaluation. If the result is weakly positive, then further
evaluation is usually needed.
A negative immunoassay result in the setting of a strongly suggestive history does not
exclude allergy. In this situation, a skin prick test should be considered (if not
contraindicated).
False-positive results of allergen-specific IgE can theoretically occur in patients with
extremely elevated total IgE levels.
Tests used largely in research settings include immunoblotting, basophil histamine or
leukotriene release tests, basophil activation, and levels of eosinophil mediators, etc., are
not standardized, and are generally not superior to skin testing, and cannot be recommended
for routine clinical use.
Allergen-specific IgG and IgG4 tests, which are believed to correlate with normal
immunologic responses to foreign substances, are not useful in the diagnosis of IgEmediated allergy, with the exception of venom allergy. Unreliable testing methods include
provocation/neutralization tests, kinesiology, cytotoxic tests, and electrodermal testing.
In food allergy, circulating IgE antibodies may remain undetectable despite a convincing
clinical history because these antibodies may be directed toward allergens that are revealed
or altered during industrial processing, cooking, or digestion and therefore do not exist in
the original food for which the patient is tested.

Identical results for different allergens may not be associated with clinically equivalent
manifestations, due to differences in patient sensitivities.

ALBUMIN, SERUM
Definition
Albumin is the most important protein and constitutes 55–65% of total plasma protein.
Approximately 300–500 g of albumin is distributed in the body fluids, and the average adult
liver synthesizes approximately 15 g/day. Albumin’s half-life is approximately 20 days,
with 4% of the total albumin pool being degraded daily. The serum albumin concentration
reflects the rate of synthesis, the degradation, and the volume of distribution. Albumin
synthesis is regulated by a variety of influences, including nutritional status, serum oncotic
pressure, cytokines, and hormones.


Normal range:
0–4 months: 2.0–4.5 g/dL
4 months−16 years: 3.2–5.2 g/dL
>16 years: 3.5–4.8 g/dL

Use
Assess nutritional status
Evaluate chronic illness
Evaluate liver disease

Interpretation
Increased In
Dehydration
High-protein diet

Decreased In

Decreased synthesis by the liver:
Acute and chronic liver disease (e.g., alcoholism, cirrhosis, hepatitis)
Malabsorption and malnutrition
Fasting, protein–calorie malnutrition
Amyloidosis
Chronic illness
DM
Decreased growth hormone levels
Hypothyroidism
Hypoadrenalism
Genetic analbuminemia
Acute-phase reaction, inflammation, and chronic diseases:
Bacterial infections
Monoclonal gammopathies and other neoplasms
Parasitic infestations
Peptic ulcer
Prolonged immobilization
Rheumatic diseases
Severe skin disease
Increased loss over body surface:
Burns
Enteropathies related to sensitivity to ingested substances (e.g., gluten sensitivity, Crohn
disease, ulcerative colitis)
Fistula (gastrointestinal or lymphatic)