Laboratory Tests

Laboratory Tests

L. V. Rao

Hongbo Yu


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.” The basis of current molecular assays is reviewed in the chapter on Hereditary and Genetic Diseases.

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.


□ 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.

    • ▼ Low values can occur in stage 4 or 5 kidney disease (eGFR below 30 mL/minute), in advanced liver disease, and during pregnancy.

    • ▼ The diabetes drugs acarbose (Glucobay) and SGLT2 inhibitors (Invokana) cause low GlycoMark values.

    • ▼ The Chinese medicines Polygala, Tenuifolia, and Senega syrup may cause high GlycoMark values.


□ Use

  • Diagnosis of and monitoring therapeutic response in congenital adrenal hyperplasia (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.


□ Use

  • Diagnosis and management of CAH, hirsutism, and infertility

□ Interpretation

Increased in

  • The luteal phase of menstruating women and pregnancy

  • When defective, 21-hydroxylase and 11-β-hydroxylase are present.

    • ▼ In the most common form of CAH, where deficiency of enzymes, 21-hyfroxylase and 11-β-hydroxylase, blocks the normal synthesis of cortisol, leading to a compensatory increase of ACTH secretion leading to increased 17-α-Hydroxyprogesterone.

□ Limitations

  • 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 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 17α-hydroxyprogesterone levels in women suspected of having late-onset CAH.


□ 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.


□ 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.


□ 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 trimester)

    • ▼ 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)

    • ▼ Use of hepatotoxic medications (e.g., acetaminophen, halothane, isoniazid [INH], methyldopa, nitrofurantoin) can increase the levels.


□ 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: 10-25 µg/mL serum in healthy adults

    • ▼ Potentially toxic: >150 µg/mL measured 4 hours post dose

    • ▼ Use of Rumack-Matthew nomogram to assess probability of toxicity

□ 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/plasma quantitation by enzyme immunoassay on an automated chemistry analyzer or HPLC.

    • ▼ Urine—Qualitative by HPLC or GC/MS.

    • 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.


□ Use

  • Predicts recurrence after radical prostatectomy for clinically localized prostate cancer and following response to androgen ablation therapy, when used in conjunction with prostate-specific antigen (PSA)

□ Interpretation

Increased in

  • Acid phosphatase is increased in the following conditions:

    • ▼ Prostate cancer

    • ▼ Gaucher disease and Niemann-Pick disease

    • ▼ 1-2 days after prostatic surgery or biopsy

    • ▼ Prostatic manipulation or catheterization

    • ▼ Benign prostatic hyperplasia, prostatitis, prostate infarct

    • ▼ Vaginal swabs from rape victims

□ Limitations

  • It is no longer used to screen for or to stage prostate cancer.

  • Levels 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.


□ Use

  • Initial test to distinguish primary from secondary adrenal insufficiency.

  • 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 lowdose 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

  • Both high- and low-dose ACTH stimulation tests had similar diagnostic accuracy. Both tests are adequate to rule in, but not rule out, secondary adrenal insufficiency.

  • 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, this testing 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 (RIAs) 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.

  • 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 lowdose 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.


□ 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 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 such as antithrombin III deficiency, clotting factor deficiencies, and 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.


□ 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.


□ Use

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

  • Individuals at risk of metabolic syndrome or diabetes due to poor lifestyle choices.

□ 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 (9 times likely)

  • Obesity and metabolic syndrome (3 times greater risk)

  • Coronary artery disease (2 times increased risk)

□ 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.


□ 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

  • Pseudo-Cushing disorders (depression, alcoholism, and anorexia nervosa)

Decreased in

  • Secondary adrenocortical insufficiency

  • Adrenal carcinoma

  • Adenoma

  • Hypopituitarism

  • Infiltrative diseases of the hypothalamus (e.g., sarcoid, histiocytosis, tuberculosis, fungal infections)

□ 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.


□ 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

  • Specific IgE levels higher than 0.35 kU/L suggest sensitization, but that is not synonymous with clinical disease.

  • The demonstration of sensitization is not sufficient to diagnose an allergy. 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.

  • 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 IgE-mediated 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.


□ 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)

    • ▼ Hemorrhage

    • ▼ Kidney disease

    • ▼ Rapid hydration or overhydration

    • ▼ Repeated thoracentesis or paracentesis

    • ▼ Trauma and crush injuries

  • Increased catabolism:

    • ▼ Fever

    • ▼ Cushing disease

    • ▼ Preeclampsia

    • ▼ Thyroid dysfunction

  • Plasma volume expansion:

    • ▼ CHF

    • ▼ Oral contraceptives

    • ▼ Pregnancy

□ Limitations

  • In clinical practice, one of the two dye-binding assays—bromocresol green (BCG) and bromocresol purple (BCP)—is used for measuring albumin levels, and systematic differences between these methods have long been recognized.

  • BCG methods are subject to nonspecific interference from binding to nonalbumin proteins, whereas BCP is more specific. BCP has been shown to underestimate serum albumin in pediatric patients on hemodialysis and patients in chronic renal failure. Chronic dialysis units often have little influence over the method.

  • Antialbumin antibodies are commonly found with hepatic dysfunction and are typically of IgA type.

  • Ischemia-modified albumin, in which the metal-binding capacity of albumin has decreased due to exposure to ischemic events, is a biologic marker of myocardial ischemia.


□ Use

  • Beverage (ethanol)

  • Solvent and reagent

  • Vehicle in chemical and pharmaceutical industries

  • Antiseptic (isopropanol)

□ Limitations

  • Testing is performed by enzyme immunoassay on automated chemistry analyzers or by headspace gas chromatography. Serum, whole blood, and urine are usually the sample matrix.

  • Immunoassay testing for ethanol may have cross-reactivity <1% with isopropanol alcohol, methanol, ethylene glycol, and acetaldehyde; <15% with n-propanol.

  • In many headspace gas chromatographic methods, acetonitrile co-elutes with acetone, leading to a false-positive result. Acetonitrile may be a component in cosmetic nail remover.

  • Alcohol (ethanol) metabolites, ethyl glucuronide (EtG) and ethyl sulfate, provide a longer window of detection compared with ethanol, and may be detected in urine by immunoassay (EtG), with confirmation by LC-MSMS.

  • Elevated concentrations of acetone are detected in specimens during diabetic ketoacidosis and fasting ketoacidosis and may range from 10 to 70 mg/dL.

  • A positive urine ethanol due to the presence of yeast in the patient’s urine has been described. In these cases, glucose was also present in the urine.


□ Use

  • Diagnosis of primary hyperaldosteronism

  • Differential diagnosis of fluid and electrolyte disorders

  • Assessment of adrenal aldosterone production

□ Interpretation

Increased in

  • Primary aldosteronism

  • Secondary aldosteronism

  • Bartter syndrome

  • Pregnancy

  • Very low-sodium diet

  • Unilateral renal artery stenosis

Decreased in

  • Hyporeninemic hypoaldosteronism (Cushing syndrome)

  • CAH

  • Congenital deficiency of aldosterone synthetase

  • Addison disease

  • Very high-sodium diet

□ Limitations

  • Many physiologic factors affect plasma aldosterone. Posture; salt intake; use of antihypertensive drugs, steroids, and oral contraceptives; age; stress; exercise; menstrual cycle; and pregnancy can all have a strong influence on aldosterone results.

  • Licorice may mimic aldosterone effects and should be avoided 2 weeks before the test.


□ Use

  • Diagnosis and treatment of the liver, bone, intestinal, and parathyroid diseases

□ Interpretation

Increased in

  • Increased bone formation

  • Bone diseases (metastatic carcinoma of the bone, myeloma, Paget disease)

  • Renal disease (renal rickets due to vitamin D-resistant rickets associated with secondary hyperparathyroidism)

  • Liver disease (e.g., infectious mononucleosis, uncomplicated extrahepatic biliary obstruction, liver abscess)

  • Miscellaneous (extrahepatic sepsis, ulcerative colitis, pancreatitis, phenytoin, and alcohol use)

  • Bone origin—increased deposition of calcium

    • ▼ Hyperparathyroidism.

    • ▼ Paget disease (osteitis deformans) (highest reported values 10-20 times normal). Marked elevation in the absence of liver disease is most suggestive of Paget disease of the bone or metastatic carcinoma from the prostate.

    • ▼ Increase in cases of metastases to bone is marked only in prostate carcinoma.

    • ▼ Osteoblastic bone tumors (osteogenic sarcoma, metastatic carcinoma).

    • ▼ Osteogenesis imperfecta (due to healing fractures).

    • ▼ Familial osteoectasia.

    • ▼ Osteomalacia and rickets.

    • ▼ Polyostotic fibrous dysplasia.

    • ▼ Osteomyelitis.

    • ▼ Late pregnancy; reverts to normal level by 20th day postpartum.

    • ▼ Children <10 years of age and again during prepubertal growth spurt may have three to four times adult values; adult values are attained by age 20.

    • ▼ Administration of ergosterol.

    • ▼ Hyperthyroidism.

    • ▼ Transient hyperphosphatasemia of infancy.

    • ▼ Hodgkin disease.

    • ▼ Healing of extensive fractures (slightly).

  • Liver disease

    • ▼ Any obstruction of the biliary system (e.g., stone, carcinoma, primary biliary cirrhosis) is a sensitive indicator of intrahepatic or extrahepatic cholestasis. Whenever the ALP is elevated, a simultaneous elevation of 5′-nucleotidase (5′-N) establishes biliary disease as the cause of the elevated ALP. If the 5′-N is not increased, the cause of the elevated ALP must be found elsewhere (e.g., bone disease):

      • Liver infiltrates (e.g., amyloid or leukemia)

      • Cholangiolar obstruction in hepatitis (e.g., infectious, toxic)

      • Hepatic congestion due to heart disease

      • Adverse reaction to therapeutic drug (e.g., chlorpropamide) (progressive elevation of serum ALP may be first indication that drug therapy should be halted); may be 2-20 times normal

      • Increased synthesis of ALP in the liver

    • ▼ Diabetes mellitus—44% of diabetic patients have 40% increase of ALP.

    • ▼ Parenteral hyperalimentation of glucose

  • Liver diseases with increased ALP

    • ▼ Less than three to four times increase lacks specificity and may be present in all forms of liver disease.

    • ▼ Two times increase: acute hepatitis (viral, toxic, alcoholic), acute fatty liver, and cirrhosis.

    • ▼ Two to ten times increase: nodules in the liver (metastatic or primary tumor, abscess, cyst, parasite, TB, sarcoid); is a sensitive indicator of a hepatic infiltrate.

    • ▼ Increase more than two times the upper limit of normal in patients with primary breast or lung tumor with osteolytic metastases is more likely caused by liver than by bone metastases.

    • ▼ Five times increase: infectious mononucleosis and postnecrotic cirrhosis.

    • ▼ Ten times increase: carcinoma of the head of the pancreas, choledocholithiasis, and drug cholestatic hepatitis.

    • ▼ Fifteen to twenty times increase: primary biliary cirrhosis and primary or metastatic carcinoma. The GGT-to-ALP ratio >2.5 is highly suggestive of alcohol abuse.

    • ▼ Chronic therapeutic use of anticonvulsant drugs (e.g., phenobarbital, phenytoin).

  • Placental origin: appears at 16th-20th week of normal pregnancy, increases progressively to two times normal up to onset of labor, and disappears 3-6 days after delivery of the placenta. ALP may be increased during complications of pregnancy (e.g., hypertension, preeclampsia, eclampsia, threatened abortion) but is difficult to interpret without serial determinations. It is lower in diabetic than in nondiabetic pregnancy.

  • Intestinal origin: is a component in approximately 25% of normal sera; increases 2 hours after eating in persons with blood type B or O who are secretors of the H blood group. ALP has been reported to be increased in cirrhosis, various ulcerative diseases of the GI tract, severe malabsorption, chronic hemodialysis, and acute infarction of the intestine.

    • ▼ Benign familial hyperphosphatasemia.

    • ▼ Ectopic production by neoplasm (Regan isoenzyme) without involvement of the liver or bone (e.g., Hodgkin disease; cancer of the lung, breast, colon, or pancreas; highest incidence in ovary and cervical cancers).

    • ▼ Vascular endothelium origin—some patients with myocardial, pulmonary, renal (one third of cases), or splenic infarction, usually after 7 days during the phase of organization.

    • ▼ Hyperphosphatasia (liver and bone isoenzymes).

    • ▼ Hyperthyroidism (liver and bone isoenzymes). Increased ALP alone in a chemical profile, especially with a decreased serum cholesterol and lymphocytosis, should suggest excess thyroid medication or hyperthyroidism.

    • ▼ Primary hypophosphatemia (often increased).

    • ALP isoenzyme determinations are not widely used clinically; heat inactivation may be more useful to distinguish bone from liver source of increased ALP

      • Extremely heat-labile (90%): bone, vascular endothelium, reticuloendothelial system.

      • Extremely heat-stable (90%): placenta, neoplasms.

      • Intermediate heat-stable (60-80%): liver, intestine.

    • ▼ Also, differentiate by chemical inhibition (e.g., l-phenylalanine) or use serum GGT and leucine aminopeptidase.

    • ▼ Children—mostly bone; little or no liver or intestine.

    • ▼ Adults—liver with little or no bone or intestine; after age 50, increasing amounts of bone.

Decreased in

  • Hypothyroidism

  • Gross anemia

  • Hypophosphatemia

  • Vitamin B12 deficiency

  • Nutritional deficiency of zinc or magnesium

  • Excess vitamin D ingestion

  • Milk-alkali (Burnett) syndrome

  • Congenital hypophosphatasia (enzymopathy of liver, bone, kidney isoenzymes)

  • Achondroplasia

  • Hypothyroidism and cretinism

  • Pernicious anemia (one third of patients)

  • Celiac disease

  • Malnutrition

  • Scurvy

  • Postmenopausal women with osteoporosis taking estrogen replacement therapy

  • Therapeutic agents (e.g., corticosteroids, trifluoperazine, antilipemic agents, some hyperalimentation)

  • Cardiac surgery with cardiopulmonary bypass pump

Normal in

  • Inherited metabolic diseases (Dubin-Johnson, Rotor, Gilbert, and Crigler-Najjar syndromes; type I-V glycogenoses, mucopolysaccharidoses; increased in Wilson disease and hemochromatosis related to hepatic fibrosis).

  • Consumption of alcohol by healthy persons (in contrast to GGT); may be normal even in alcoholic hepatitis.

  • In acute icteric viral hepatitis, the increase is less than two times normal in 90% of cases, but when ALP is high and serum bilirubin is normal, infectious mononucleosis should be ruled out as a cause of hepatitis.

□ Limitations

  • The elevation in ALP tends to be more marked (more than threefold) in extrahepatic biliary obstruction (e.g., by stone or by cancer of the head of the pancreas) than in intrahepatic obstruction, and it is greater the more complete the obstruction. Serum enzyme activities may reach 10-12 times the upper limit of normal, returning to normal on surgical removal of the obstruction.

  • Day-to-day variation is 5-10%.

  • Recent food ingestion can increase as much as 30 U/L.

  • ALP is 15% and 10% higher in African American men and women, respectively, compared to other racial/ethnic groups.

  • Twenty-five percent higher with increased body mass index, 10% higher with smoking, and 20% lower with the use of oral contraceptives.

  • Common drugs, including penicillin derivatives, antiepileptic drugs, antihistamines, cardiovascular drugs, etc., can increase blood levels.


□ Use

  • Workup of individuals with suspected disorders such as familial chronic obstructive lung disease, emphysema, asthma, and bronchiectasis

  • Diagnosis of AAT deficiency

  • Diagnosis of juvenile and adult cirrhosis of the liver

□ Interpretation

Increased in

  • Inflammation (acute-phase reacting protein)

  • Infection, tissue injury or necrosis, rheumatic disease, and some malignancies

  • Estrogen administration (oral contraceptives, pregnancy, especially third trimester)

Decreased in

  • Deficiency states (hereditary)

  • Hepatic disease (hepatitis, cholestasis, cirrhosis, or hepatic cancer)

  • Pulmonary emphysema and chronic obstructive pulmonary disease (COPD)

□ Limitations

  • Phenotypic studies are recommended to confirm a suspected hereditary deficiency.

  • False-positive results can occur if rheumatoid factor is present.

  • Given the variability in reference ranges, patients with a serum AAT level below 100 mg/dL should be evaluated further with isoelectric focusing or genotyping.


□ Use

  • Marker for hepatocellular and germ cell (nonseminoma) carcinoma.

  • Follow-up management of patients undergoing cancer therapy, especially for testicular and ovarian tumors and for HCC. The measurement of AFP in serum, in conjunction with serum human chorionic gonadotropin, is an established regimen for monitoring patients with nonseminomatous testicular cancer. In addition, monitoring the rate of AFP clearance from serum after treatment is an indicator of the effectiveness of therapy. Conversely, the growth rate of progressive cancer can be monitored by serially measuring serum AFP concentration over time.

  • Serial serum AFP testing is a useful adjunctive test for managing nonseminomatous testicular cancer.

□ Interpretation

  • AFP is increased in the following disorders:

    • ▼ Ataxia-telangiectasia

    • ▼ Hereditary tyrosinemia

    • ▼ Primary HCC

    • ▼ Teratocarcinoma

    • ▼ Gastrointestinal tract cancers with and without liver metastases

    • ▼ Benign hepatic conditions such as acute viral hepatitis, chronic active hepatitis, and cirrhosis

□ Limitations

  • AFP is not recommended as a screening procedure to detect cancer in the general population. This assay is intended only as an adjunct in the diagnosis and monitoring of AFP-producing tumors. The diagnosis should be confirmed by other tests or procedures.

  • Serum levels of AFP do not correlate well with other clinical features of HCC, such as size, stage, or prognosis.

  • A case-control study evaluated the diagnostic characteristics of the serum AFP in screening for HCC in patients with different types of chronic liver disease. The following sensitivities and specificities were observed:

    • AFP cutoff 16 µg/L (sensitivity 62%, specificity 89%)

    • AFP cutoff 20 µg/L (sensitivity 60%, specificity 91%)

    • AFP cutoff 100 µg/L (sensitivity 31%, specificity 99%)

    • AFP cutoff 200 µg/L (sensitivity 22%, specificity 99%)

  • False-positive elevations can occur with tumors of the GI tract or with liver damage (e.g., cirrhosis, hepatitis, or drug or alcohol abuse) and pregnancy. Lysis of tumor cells during the initiation of chemotherapy may result in a transient increase in serum AFP.

  • Failure of the AFP value to return to normal by approximately 1 month after surgery suggests the presence of residual tumor.

  • Elevation of AFP after remission suggests tumor recurrence; however, tumors originally producing AFP may recur without an increase in AFP.

  • Fucosylated form of serum AFP that is most closely associated with HCC is recognized by a lectin from the common lentil (AFP-L3). AFP-L3 is most useful in the differential diagnosis of individuals with total serum AFP ≤ 200 ng/mL.

Suggested Reading

Trevisani F, D’Intino PE, Morselli-Labate AM, et al. Serum alpha-fetoprotein for diagnosis of hepatocellular carcinoma in patients with chronic liver disease: influence of HBsAg and anti-HCV status. J Hepatol. 2001;34(4):570-575.


□ Use

  • Most sensitive tests for acute hepatocellular injury (e.g., viral, drug); precedes increase in serum bilirubin by approximately 1 week

□ Interpretation

Increased in

  • Hepatocellular damage, liver cell necrosis, or injury of any cause.

  • Alcoholic hepatitis (AST > ALT).

  • Viral and chronic hepatitis (ALT > AST).

  • Early acute hepatitis: AST is usually higher initially, but by 48 hours, ALT is usually higher.

  • AST levels of 500 U/L suggest acute hepatocellular injury; seldom >500 U/L in obstructive jaundice, cirrhosis, viral hepatitis, AIDS, and alcoholic liver disease.

  • Acute fulminant viral hepatitis: Abrupt AST rise may be seen (rarely >4,000 IU/L) and declines more slowly; positive serologic tests and acute chemical injury.

  • Congestive heart failure, arrhythmia, sepsis, and GI hemorrhage AST levels reach to a peak of 1,000-9,000 U/L, declining by 50% within 3 days and to <100 U/L within a week, suggesting shock liver with centrolobular necrosis. Serum bilirubin and ALP reflect underlying disease.

  • Trauma to skeletal or heart muscle.

  • Acute heart failure (AST > ALT).

  • Severe exercise, burns, and heat stroke.

  • Hypothyroidism.

  • Drug-induced injury to the liver.

  • Acute bile duct obstruction due to a stone: Rapid rise of AST and ALT to very high levels (e.g., >600 U/L and often >2,000 U/L) followed by a sharp fall in 12-72 hours is said to be typical.

Decreased in

  • Azotemia

  • Chronic renal dialysis

  • Pyridoxal phosphate deficiency states (e.g., malnutrition, pregnancy, alcoholic liver disease)

□ Limitations

  • Half-life of AST is 18 hours and that of ALT is 48 hours.

  • The patient is rarely asymptomatic with ALT and AST levels >1,000 U/L.

  • AST >10 times normal indicates acute hepatocellular injury, but lesser increases are nonspecific and may occur with virtually any form of liver injury.

  • Increases ≤8 times upper limit of normal are nonspecific; may be found in any liver disorder.

  • Rarely increased >500 U/L (usually <200 U/L) in posthepatic jaundice, AIDS, cirrhosis, and viral hepatitis.

  • Usually <50 U/L in fatty liver.

  • Less than 100 U/L in alcoholic cirrhosis; ALT is normal in 50%, and AST is normal in 25% of these cases.

  • Less than 150 U/L in alcoholic hepatitis (may be higher if the patient has delirium tremens).

  • Less than 200 U/L in approximately 50% of patients with cirrhosis, metastatic liver disease, lymphoma, and leukemia.

  • Normal values may not rule out liver disease: ALT is normal in 50%, and AST is normal in 25% of cases of alcoholic cirrhosis.

  • Degree of increase has a poor prognostic value.

  • Serial determinations reflect clinical activity of liver disease. Persistent increase may indicate chronic hepatitis.

  • Mild increase of AST and ALT (usually <500 U/L) with ALP increased greater than three times normal indicates cholestatic jaundice, but more marked increase of AST and ALT (especially >1,000 U/L) with ALP increased less than three times normal indicates hepatocellular jaundice.

  • Rapid decline in AST and ALT is a sign of recovery from disease but in acute fulminant hepatitis may represent loss of hepatocytes and poor prognosis.

  • Poor correlation of increased concentration with extent of liver cell necrosis and has a little prognostic value.

  • Although AST, ALT, and bilirubin are most characteristic of acute hepatitis, they are unreliable markers of severity of injury.

  • ALT has 45% variation during the day; highest in afternoon and lowest at night. Both AST and ALT exhibit 10-30% variation from 1 day to next. AST levels are 15% higher in African American men.


□ Use

  • In the diagnosis of hepatic encephalopathy and hepatic coma in the terminal stages of liver cirrhosis, hepatic failure, acute and subacute necrosis, and Reye syndrome. Hyperammonemia in infants may be an indicator of inherited deficiencies of the urea cycle metabolic pathway.

  • Should be measured in cases of unexplained lethargy and vomiting, encephalopathy, or any neonate with unexplained neurologic deterioration.

  • Not useful to assess the degree of dysfunction (e.g., in Reye syndrome, hepatic function improves and the ammonia level falls, even in patients who finally die of these disorders).

□ Interpretation

Increased in

  • Certain inborn errors of metabolism (e.g., defects in urea cycle, organic acid defects).

  • Transient hyperammonemia in newborn; unknown etiology; may be life threatening in the first 48 hours.

  • May occur in any patient with severe liver disease (e.g., acute hepatic necrosis, terminal cirrhosis, and after portacaval anastomosis). Increased in most cases of hepatic coma but correlates poorly with degree of encephalopathy. Not useful in known liver disease but may be useful in encephalopathy of unknown cause.

  • Moribund children: Moderate increases (≤300 µmol/L) without being diagnostic of a specific disease.

  • GU tract infection with distention and stasis.

  • Ureterosigmoidostomy.

  • Some hematologic disorders, including acute leukemia and after bone marrow transplantation.

  • Total parenteral nutrition.

  • Smoking, exercise, and valproic acid therapy.

  • An elevated plasma ammonia concentration combined with normal blood glucose and anion gap strongly suggests a urea cycle disorder.

Decreased in

  • Hyperornithinemia (deficiency of ornithine aminotransaminase activity) with gyrate atrophy of the choroid and retina

□ Limitations

  • Atmospheric ammonia may cause falsely elevated results.

  • The presence of ammonium ions in anticoagulants may produce falsely elevated results.

  • Ammonia levels are not always high in all patients with urea cycle disorders.

  • High-protein diet may cause increased levels.

  • Ammonia levels may also be elevated with GI hemorrhage.

  • Ammonia increases due to cellular metabolism: 20% in 1 hour and 100% by 2 hours.

  • Prolonged tourniquet application can falsely raise blood ammonia levels.

  • Plasma ammonia is >100-150 µmol/L; further testing is performed to establish a diagnosis. Mild elevations below this threshold should be interpreted in the context of the clinical course and followed to ensure resolution.


□ Use

  • Appetite suppressants.

  • Mood enhancers (psychotropics).

  • Treatment of attention deficit hyperactivity disorder.

  • Nasal decongestants, bronchodilators.

□ Limitations

  • Screen [urine]: Immunoassay on automated chemistry analyzers.

    • ▼ Amphetamine: Generally do not give positive results for L-amphetamine, MDA, MDMA, ephedrine, and phentermine.

    • ▼ Ecstasy: The target analyte of most immunoassays is MDMA. Screen will not give positive results with D/L-amphetamine, D/L-methamphetamine, phentermine, ephedrine, pseudoephedrine, PMA, and PMMA.

  • Screen [serum]: ELISA.

    • ▼ Target analyte: D-amphetamine. Will not give positive results with L-amphetamine, L-methamphetamine, phenylpropanolamine, MDMA, and MDE.

    • ▼ May produce positive results with MDA.

  • Confirmation [serum/urine]:

    • ▼ Confirmation techniques do not typically differentiate between D and L forms of amphetamine and methamphetamine. Specific chromatographic characteristics are required.


□ Use

  • To diagnose and monitor pancreatitis or other pancreatic diseases

  • In the workup of any intra-abdominal inflammatory event

□ Interpretation

Increased in

  • Acute pancreatitis (e.g., alcoholic, autoimmune). Urine levels reflect serum changes by a time lag of 6-10 hours.

  • Acute exacerbation of chronic pancreatitis.

  • Drug-induced acute pancreatitis (e.g., aminosalicylic acid, azathioprine, corticosteroids, dexamethasone, ethacrynic acid, ethanol, furosemide, thiazides, mercaptopurine, phenformin, triamcinolone).

  • Drug-induced methodologic interference (e.g., pancreozymin [contains amylase], chloride and fluoride salts [enhance amylase activity], lipemic serum [turbidimetric methods]).

  • Obstruction of pancreatic duct by:

    • ▼ Stone or carcinoma

      • Drug-induced spasm of the sphincter of Oddi (e.g., opiates, codeine, methyl choline, cholinergics, chlorothiazide) to levels 2-15 times normal

      • Partial obstruction + drug stimulation

    • ▼ Biliary tract disease

    • ▼ Common bile duct obstruction

    • ▼ Acute cholecystitis

  • Complications of pancreatitis (pseudocyst, ascites, abscess).

  • Pancreatic trauma (abdominal injury; following endoscopic retrograde cholangiopancreatography [ERCP]).

  • Altered GI tract permeability:

    • ▼ Ischemic bowel disease or frank perforation

    • ▼ Esophageal rupture

    • ▼ Perforated or penetrating peptic ulcer

    • ▼ Postoperative upper abdominal surgery, especially partial gastrectomy (≤2 times normal in one third of patients)

  • Acute alcohol ingestion or poisoning.

  • Salivary gland disease (mumps, suppurative inflammation, duct obstruction due to calculus, radiation).

  • Malignant tumors (especially pancreas, lung, ovary, esophagus; also breast, colon); usually >25 times upper reference limit, which is rarely seen in pancreatitis.

  • Advanced renal insufficiency; often increased even without pancreatitis.

  • Macroamylasemia.

  • Others, such as chronic liver disease (e.g., cirrhosis; ≤2 times normal), burns, pregnancy (including ruptured tubal pregnancy), ovarian cyst, diabetic ketoacidosis, recent thoracic surgery, myoglobinuria, presence of myeloma proteins, some cases of intracranial bleeding (unknown mechanism), splenic rupture, and dissecting aneurysm.

  • Increased serum amylase with low urine amylase may be seen in renal insufficiency and macroamylasemia. Serum amylase ≤4 times normal in renal disease only when creatinine clearance (CrCl) is <50 mL/minute due to pancreatic or salivary isoamylase; but rarely more than four times normal in the absence of acute pancreatitis.

Decreased in

  • Extensive marked destruction of the pancreas (e.g., acute fulminant pancreatitis, advanced chronic pancreatitis, advanced cystic fibrosis). Decreased levels are clinically significant only in occasional cases of fulminant pancreatitis.

  • Severe liver damage (e.g., hepatitis, poisoning, toxemia of pregnancy, severe thyrotoxicosis, severe burns).

  • Methodologic interference by drugs (e.g., citrate and oxalate decrease activity by binding calcium ions):

    • ▼ Normal: 1-5%

    • ▼ Macroamylasemia: <1%; very useful for this diagnosis

    • ▼ Acute pancreatitis: >5%; use is presently discouraged for this diagnosis

  • Amylase-to-creatinine clearance ratio = (urine amylase/serum amylase) (serum creatinine/urine creatinine) × 100

Normal in

  • Relapsing chronic pancreatitis

  • Patients with hypertriglyceridemia (technical interference with test)

  • Frequently normal in acute alcoholic pancreatitis

□ Limitations

  • Composed of pancreatic and salivary types of isoamylases distinguished by various methodologies; nonpancreatic etiologies are almost always salivary; both types may be increased in renal insufficiency.

  • An elevation of total serum α-amylase does not specifically indicate a pancreatic disorder, since the enzyme is produced by the salivary glands, mucosa of the small intestine, ovaries, placenta, liver, and the lining of the fallopian tubes.

  • Pancreatic amylase results may be elevated in patients with macroamylase. This elevated pancreatic amylase is not diagnostic for pancreatitis. By utilizing serum lipase and urinary amylase values, the presence or absence of macroamylase may be determined.

  • Current guidelines and recommendations indicate that lipase should be preferred over total and pancreatic amylase for the initial diagnosis of acute pancreatitis and that the assessment should not be repeated over time to monitor disease prognosis.


□ Use

  • Differential diagnosis of pancreatitis

  • Diagnosis of pseudocyst of the pancreas, where the urine amylase may remain elevated for weeks after the serum amylase has returned to normal, after a bout of acute pancreatitis.

□ Interpretation

Increased in

  • Pancreatitis (>6%)

  • DKA

  • Renal insufficiency

  • Duodenal perforation

  • Large doses of corticosteroids

  • Pancreatic cancer

  • Myeloma and light chain disease

Decreased in

  • Macroamylasemia

□ Limitations

  • Macroamylasemia is characterized by high serum amylase but normal urine amylase. The ALCR remains useful for the diagnosis of macroamylasemia. In macroamylasemia, the clearance is very low.


□ Use

  • Diagnosis of virilism and hirsutism

  • Suspicion of anabolic steroid abuse

  • Diagnosis of CAH, in conjunction with measurement of other androgenic precursors

TABLE 2-4. Normal Ranges for Serum Androstenedione

Age/Tanner Stage

Female (ng/mL)

Male (ng/mL)

7-9 y



10-11 y



12-13 y



14-15 y



16-17 y



18-40 y



≥41 y



Postmenopausal women


Tanner stage I



Tanner stage II



Tanner stage III



Tanner stage IV-V



□ Interpretation

Increased in

  • CAH caused by 21-hydroxylase deficiency; marked increase is suppressed to normal levels by adequate glucocorticoid therapy:

    • ▼ Suppressed level reflects adequacy of therapeutic control.

    • ▼ Androstenedione may be better than 17-hydroxyprogesterone for monitoring therapy because it shows minimal diurnal variation, better correlation with urinary 17-KS excretion, and plasma levels that are not immediately affected by a dose of glucocorticoid.

  • Adrenal tumors

  • Cushing disease

  • Polycystic ovarian disease

Decreased in

  • Addison disease

  • Any condition that causes partial or complete adrenal or gonadal failure


□ Use

  • Evaluating hypertension

□ Interpretation

Increased in

  • Hypertension

  • Renin-secreting juxtaglomerular renal tumor

  • Volume depletion

  • CHF

  • Cirrhosis

Decreased in

  • Anephric patients

  • Primary aldosteronism

  • Cushing syndrome

□ Limitations

  • Patient should be on normal-sodium diet and be recumbent for 30 minutes before specimen collection.

  • Short-lived in plasma (half-life is 5 minutes) and degraded into inactive peptides, plasma should be separated and frozen immediately.


□ Use

  • Evaluation of patients with suspected sarcoidosis

  • Evaluation of the severity and activity of sarcoidosis

  • Evaluation of hypertension

  • Evaluation of Gaucher disease

□ Interpretation

Increased in

  • Active pulmonary sarcoidosis (50-75% of patients but only 11% with inactive disease)

  • Gaucher disease (100%)

  • DM (>24%)

  • Hyperthyroidism (81%)

  • Leprosy (53%)

  • Chronic renal disease

  • Cirrhosis (25%)

  • Silicosis (>20%)

  • Berylliosis (75%)

  • Amyloidosis

  • TB infection

  • Connective tissue diseases

  • Fungal disease and histoplasmosis

Decreased in

  • Far-advanced lung neoplasms

  • Anorexia nervosa associated with hypothyroidism

  • COPD, emphysema, lung cancer, cystic fibrosis

  • Starvation

□ Limitations

  • False-positive rate equals 2-4%.

  • Levels may be normal in lymphoma and lung cancer.

  • Serum ACE is significantly reduced in patients on ACE inhibitors (e.g., enalapril and captopril).

  • The reference interval for children and adolescents may be as much as 50% higher than specimens from adults.

  • Serum ACE abnormality has been reported in 20-30% of α1-antitrypsin variants (MZ, ZZ, and MS Pi types) but in only about 1% of individuals with normal MM Pi type. There is evidence that paraquat poisoning (because of its effect on pulmonary capillary endothelium) is associated with elevated serum ACE.


□ Use

  • Identify cause of a metabolic acidosis

  • Supplement to laboratory quality control, along with its components

□ Interpretation

Increased in

  • Organic (e.g., lactic acidosis, ketoacidosis)

  • Inorganic (e.g., administration of phosphate, sulfate)

  • Protein (e.g., hyperalbuminemia, transient)

  • Exogenous (e.g., salicylate, formate, paraldehyde, nitrate, penicillin, carbenicillin)

  • Not completely identified (e.g., hyperosmolar hyperglycemic nonketotic coma, uremia, poisoning by ethylene glycol, methanol)

  • Artifactual

    • ▼ Falsely increased serum sodium

    • ▼ Falsely decreased serum chloride or bicarbonate

  • When AG >12-14 mmol/L, diabetic ketoacidosis is the most common cause, uremic acidosis is the second most common cause, and drug ingestion (e.g., salicylates, methyl alcohol, ethylene glycol, ethyl alcohol) is the third most common cause; lactic acidosis should always be considered when these three causes are ruled out. In small children, rule out inborn errors of metabolism.

Decreased in

  • Hypoalbuminemia (most common cause), hypocalcemia, and hypomagnesemia.

  • Artifactual (laboratory error, most frequent cause).

  • “Hyperchloremia” in bromide intoxication (if chloride determination by colorimetric method).

  • False increase in serum chloride or HCO3.

  • False decrease in serum sodium (e.g., hyperlipidemia, hyperviscosity):

    • ▼ Increased unmeasured cations

    • ▼ Hyperkalemia, hypercalcemia, and hypermagnesemia

  • Increased proteins in multiple myeloma, paraproteinemias, and polyclonal gammopathies (these abnormal proteins are positively charged and lower the AG).

  • Lithium and bromide overdose.

  • Simultaneous changes in ions may cancel each other out, leaving AG unchanged (e.g., increased Cl and decreased HCO3). The change in AG should equal change in HCO3; otherwise, a mixed, rather than simple, acid-base disturbance is present.


Mar 20, 2021 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Laboratory Tests

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