16 Laboratory Tests

Definition


Square bullet1,5-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.


Square bulletNormal range: 10.7–32.0 μg/mL in males; 6.8–29.3 μg/mL in females.


imageUse


Square bulletUsed clinically to monitor short-term glycemic control in patients with diabetes (1–2 weeks)


Square bulletUseful marker for postprandial hyperglycemia


Square bulletPerforms better than hemoglobin A1C for monitoring glucose profile in pregnancies complicated by type 1 diabetes


imageInterpretation


Increased In


Square bullet1,5-AG may be increased during IV hyperalimentation.


Decreased In


Square bulletIndividuals 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.


Square bulletα-Glucosidase inhibitors can decrease 1,5-AG by interfering with its intestinal absorption.


imageLimitations


Square bulletIn patients with poorly controlled DM, 1,5-AG is less sensitive to modest changes in glycemic control because of continuous glycosuria.


Square bulletLevels can be influenced by factors such as dairy product, races, uric acid, triglycerides, liver disease, gastrectomy state, and cystic fibrosis.


11-DEOXYCORTISOL


imageDefinition


Square bullet11-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 17-hydroxyprogesterone. 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.


Square bulletNormal range: <50 ng/dL in males; <33 ng/dL in females.


imageUse


Square bulletDiagnosis of and monitoring therapeutic response in CAH due to 11β-hydroxylase deficiency


Square bulletAssessment of adrenal response in the metyrapone test; result after metyrapone stimulation is >8,000 ng/dL


imageInterpretation


Increased In


Square bulletValues are increased in CAH (P450cII deficiency) and following metyrapone administration in normal persons.


Decreased In


Square bulletValues are decreased in adrenal insufficiency.


imageLimitations


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


17α-HYDROXYPROGESTERONE


imageDefinition


Square bullet17α-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.


Square bulletNormal range: 18–469 ng/dL (see Table 16.1).



TABLE 16–1. Range of Normal Values for 17a-Hydroxyprogesterone


image


imageUse


Square bulletDiagnosis and management of congenital adrenal hyperplasia, hirsutism, and infertility


imageInterpretation


Increased In


Square bulletThe luteal phase of menstruating women and pregnancy, during which it rises.


Square bulletWhen defective 21-alpha hydroxylase and 11-beta hydroxylase are present.


Square bulletThe 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.


imageLimitations


Square bulletCirculating 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.


Square bulletSpuriously 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.


Square bullet17α-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.


17-KETOSTEROIDS, URINE (17-KS)


imageDefinition


Square bullet17-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.


Square bulletNormal range: depends on sex and age (Table 16.2).



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


image


imageUse


Square bulletEvaluation of glucocorticoid production and neuroendocrine function


Square bulletEvaluation of androgenic adrenal and testicular function in normal male individuals and primarily adrenal androgenic secretion in normal female individuals


imageInterpretation


Increased In


Square bulletAdrenal tumor


Square bulletCongenital adrenal hyperplasia (very rare)


Square bulletCushing syndrome


Square bulletOvarian cancer


Square bulletTesticular cancer


Square bulletOvarian dysfunction (polycystic ovarian disease)


Decreased In


Square bulletAddison disease


Square bulletCastration


Square bulletHypopituitarism


Square bulletMyxedema


Square bulletNephrosis


imageLimitations


Square bulletA large number of substances may interfere with this test.


Square bulletDecreases may be caused by carbamazepine, cephaloridine, cephalothin, chlormerodrin, digoxin, glucose, metyrapone, promazine, propoxyphene, reserpine, and others.


Square bulletIncreases 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*


imageDefinition


Square bulletMutations, 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).


Square bulletNormal values: negative or no mutations are found.


imageUse


Square bulletSuspected coronary artery disease, homocystinuria, neural tube defects, spontaneous abortion, or MTHFR deficiency


imageLimitations


Square bulletThe 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


imageDefinition


Square bullet5-Hydroxyindoleacetic acid (5-HIAA), also known as serotonin metabolite, is the major urinary metabolite of serotonin.


Square bulletNormal range: 0.0–15.0 mg/day (24-hour urine); 0.0–14.0 mg/g creatinine.


imageUse


Square bulletHelps diagnose and monitor treatment for serotonin-secreting carcinoid tumors


imageInterpretation


Increased In


Square bulletWhipple disease


Square bulletNontropical sprue


Square bulletSmall increases possible in pregnancy, ovulation, and postsurgical stress


Square bulletVarious food ingestions (e.g., pineapples, kiwi, bananas, eggplant, plums, tomatoes, avocados, plantains, walnuts, pecans, hickory nuts, coffee)


Square bulletUse 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


Square bulletUse of certain drugs (e.g., chlorpromazine, promazine, imipramine, isoniazid, monoamine oxidase inhibitors, methenamine, methyldopa, phenothiazines, promethazine)


Square bulletRenal insufficiency (possible)


imageLimitations


Square bulletFoods 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.


Square bulletTwenty-four–hour collections are generally recommended, but random collections may be used. Refrigeration is the most important aspect of specimen preservation.


Square bulletUrinary 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.


Square bulletSensitivity is 73%.


Square bulletThe test is useful in the diagnosis of only 5–7% of patients with carcinoid tumors but in approximately 45% of those with liver metastases.


Square bulletDisease 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)


imageDefinition


Square bulletThis 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.


Square bulletNormal range: 2.0–8.0 U/L.


imageUse


Square bulletDetermining cholestatic liver disease, particularly when GGT and ALP could be falsely elevated due to drug induction


Square bulletBetter test for secondary tumors and lymphomas of the liver than ALP


imageInterpretation


Increased In


Square bullet5′-NT is increased in the following conditions:



imageHepatobiliary disease with intrahepatic or extrahepatic biliary obstruction


imageHepatic carcinoma


imageEarly biliary cirrhosis


imagePregnancy (third semester)


imageInflammatory arthritis


imageLimitations


Square bullet5′-NT can be elevated in hyperammonemia due to analytical interference.


Square bulletNormal in pregnancy and postpartum period (in contrast to serum leucine aminopeptidase and ALP).


ACETAMINOPHEN (N-ACETYL-p-AMINOPHENOL; APAP)


imageDefinition


Square bulletNonopioid analgesic, antipyretic


imageUse


Square bulletRelief of pain, such as headaches and toothaches


Square bulletReduction of fever


imageInterpretation


Square bulletScreen of urine: indication of exposure


Square bulletScreen of serum: used to assess potential toxicity


Square bulletNormal range: 5–20 μg/mL serum


Square bulletPotentially toxic: >150 μg/mL measured 4 hours postdose


imageLimitations


Square bulletScreening



imageSerum/urine: colorimetric or immunoassay on automated chemistry analyzers



Square bulletHigh bilirubin concentrations [>50 μg/mL] may cause false-positive results with immunoassay-based tests.


Square bulletPlasma may be tested in place of serum. Anticoagulants such as EDTA and heparin do not generally interfere with the assay.


Square bulletDo not use whole blood.


Square bulletConfirmation:



imageSerum/urine–HPLC or GC/MC


imageAPAP is highly conjugated by glucuronidation and sulfation.


imageAn assay that includes a hydrolysis step provides total APAP levels, which are not useful for assessing toxicity.


ACETYLSALICYLIC ACID


See Salicylates (Aspirin).


ACID PHOSPHATASE


imageDefinition


Square bulletAcid 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.


Square bulletNormal range: 0–0.8 U/L.


imageUse


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


imageInterpretation


Increased In


Square bulletAcid phosphatase is increased in the following conditions:



imageProstate cancer


imageGaucher disease and Niemann-Pick disease


imageOne day to 2 days after prostatic surgery or biopsy


imageProstatic manipulation or catheterization


imageBenign prostatic hyperplasia, prostatitis, prostate infarct


imageVaginal swabs from rape victims.


imageLimitations


Square bulletPAP is no longer used to screen for or to stage prostate cancer. In most instances, serum PSA is used instead.


Square bulletPAP 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.


Square bulletPAP 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


imageDefinition


Square bulletCosyntropin 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.


imageUse


Square bulletThis is the initial test used to distinguish primary from secondary adrenal insufficiency.


Square bulletIt 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


Square bulletThis test involves physiologic plasma concentrations of ACTH and provides a more sensitive index of adrenocortical responsiveness.


Square bulletIt 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.


Square bulletThere 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


Square bulletThis 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.


Square bulletThe 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.


Square bulletSalivary 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


Square bulletThe 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.


Square bulletThe 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


Square bulletThe 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.


Square bulletThis 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.


Square bulletUrinary excretion of 17-hydroxycorticoid should exceed 27 mg during the first 24 hours of infusion and 47 mg during the second 48 hours.


imageInterpretation


Square bulletLow-dose stimulation test: A value of 18 μg/dL or more, before or after ACTH injection, is indicative of normal adrenal function.


Square bulletHigh-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.


Square bulletEight-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.


Square bulletTwo-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.


imageLimitations


Square bulletIn 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.


Square bulletThe 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.


Square bulletVariability 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.


Square bulletIn women, the response to ACTH is affected by the use of oral contraceptives, which increase cortisol-binding globulin levels.


Square bulletThe 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.


Square bulletA 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.


Square bulletCortisol 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.


Square bulletThe 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)*


imageDefinition


Square bulletActivated 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.


Square bulletNormal range in the absence of heparin (with Medtronic coagulometer): 74–125 seconds.


imageUse


Square bulletACT 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.


imageInterpretation


Square bulletThere 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.


imageLimitations


Square bulletThe response of ACT to heparin varies from individual to individual and with heparin potency.


Square bulletUnderlying coagulopathies (antithrombin III deficiency, clotting factor deficiencies, DIC) must be excluded.


Square bulletMedications that inhibit platelet function (aspirin, NSAIDs) may affect ACT.


Square bulletPreanalytical 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)*


imageDefinition


Square bulletAPCR 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.


Square bulletNormal value: >1.8.


imageUse


Square bulletAPCR 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.


imageLimitations


Square bulletProtein 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.


Square bulletThe 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


imageDefinition


Square bulletAdiponectin, 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.


Square bulletNormal range: see Table 16.3.



TABLE 16–3. Normal Range of Adiponectin


image


imageUse


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


imageInterpretation


Increased In


Square bulletTwofold before a meal and decreases to trough levels within 1 hour after eating


Square bulletMore than twofold in hemodialysis patients


Decreased In


Square bulletType 2 diabetes mellitus


Square bulletObesity and metabolic syndrome


imageLimitations


Square bulletAdiponectin 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.


Square bulletDue 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)


imageDefinition


Square bulletACTH 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.


Square bulletNormal range: <46 pg/mL.


imageUse


Square bulletDiagnosis of Addison disease, CAH, Cushing syndrome, adrenal carcinoma, and ectopic ACTH syndrome


imageInterpretation


Increased In


Square bulletAddison disease


Square bulletCAH


Square bulletPituitary-dependent Cushing disease


Square bulletEctopic ACTH–producing tumors


Square bulletNelson syndrome


Decreased In


Square bulletSecondary adrenocortical insufficiency


Square bulletAdrenal carcinoma


Square bulletAdenoma


Square bulletHypopituitarism


imageLimitations


Square bulletPlasma 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.


Square bulletBecause ACTH is released in bursts, its levels in the blood can vary from minute to minute.


Square bulletACTH is unstable in blood, and proper handling of specimen is important.


Square bulletMost commercial RIAs are insensitive and nonspecific, measuring intact ACTH as well as precursors and fragments. Highly sensitive IRMAs measure intact ACTH only.


Square bulletRIAs 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.


Square bulletPatients taking glucocorticoids may have suppressed levels of ACTH with an apparent high level of cortisol.


Square bulletPregnancy, menstruation, and stress increase secretion.


ALLERGEN TESTS, SPECIFIC IMMUNOGLOBULIN E (IgE)


imageDefinition


Square bulletAllergic 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.


Square bulletMost 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.


Square bulletIn vitro testing for allergy has certain advantages:



imageIt poses no risk to the patient of an allergic reaction.


imageIt is not affected by medications (antihistamines, etc.) the patient may be taking.


imageIt is not reliant upon skin integrity or affected by skin disease.


imageIt 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.


Square bulletClinical performance of specific IgE-based serum allergen tests typically has sensitivity ranging from 84% to 95% and specificity ranging from 85% to 94%.


Square bulletVarious types of specific panels, mixes, as well as specific allergen tests currently performed at various labs and contact your lab for details.


Normal range:


image


imageUse


Square bulletTo establish the diagnosis of an allergic disease and to define the allergens responsible for eliciting signs and symptoms


Square bulletTo identify allergens that may be responsible for allergic disease and/or anaphylactic episode and to confirm sensitization to particular allergens prior to beginning immunotherapy


Square bulletTo investigate the specificity of allergic reactions to insect venom allergens, drugs, or chemical allergens


imageInterpretation


Increased In


Square bulletDetection 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


Square bulletNA.


imageLimitations


Square bulletThe 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.


Square bulletIf 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.


Square bulletA 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).


Square bulletFalse-positive results of allergen-specific IgE can theoretically occur in patients with extremely elevated total IgE levels.


Square bulletTests 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.


Square bulletAllergen-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.


Square bulletIn 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.


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


ALBUMIN, SERUM


imageDefinition


Square bulletAlbumin 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.


Square bulletNormal range:



image0–4 months: 2.0–4.5 g/dL


image4 months−16 years: 3.2–5.2 g/dL


image>16 years: 3.5–4.8 g/dL


imageUse


Square bulletAssess nutritional status


Square bulletEvaluate chronic illness


Square bulletEvaluate liver disease


imageInterpretation


Increased In


Square bulletDehydration


Square bulletHigh-protein diet


Decreased In


Square bulletDecreased synthesis by the liver:



imageAcute and chronic liver disease (e.g., alcoholism, cirrhosis, hepatitis)


imageMalabsorption and malnutrition


imageFasting, protein–calorie malnutrition


imageAmyloidosis


imageChronic illness


imageDM


imageDecreased growth hormone levels


imageHypothyroidism


imageHypoadrenalism


imageGenetic analbuminemia


Square bulletAcute-phase reaction, inflammation, and chronic diseases:



imageBacterial infections


imageMonoclonal gammopathies and other neoplasms


imageParasitic infestations


imagePeptic ulcer


imageProlonged immobilization


imageRheumatic diseases


imageSevere skin disease


Square bulletIncreased loss over body surface:



imageBurns


imageEnteropathies related to sensitivity to ingested substances (e.g., gluten sensitivity, Crohn disease, ulcerative colitis)


imageFistula (gastrointestinal or lymphatic)


imageHemorrhage


imageKidney disease


imageRapid hydration or overhydration


imageRepeated thoracentesis or paracentesis


imageTrauma and crush injuries


Square bulletIncreased catabolism:



imageFever


imageCushing disease


imagePreeclampsia


imageThyroid dysfunction


Square bulletPlasma volume expansion:



imageCHF


imageOral contraceptives


imagePregnancy


imageLimitations


Square bulletIn 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.


Square bulletBCG 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.


Square bulletAntialbumin antibodies are commonly found with hepatic dysfunction and are typically of IgA type.


Square bulletIschemia-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.


ALCOHOLS (VOLATILES, SOLVENTS)*


imageDefinition


Square bulletAlcohols are organic compounds that contain the −OH group, including methanol (CH3 OH), ethanol (ethyl alcohol; C2 H5 OH), isopropanol (rubbing alcohol), and methanol (wood alcohol). Although acetone (CH3 COCH3 ) is a ketone, not an alcohol, it is included in this group, because it is often detected in the same testing methodology.


Square bulletNormal range:



imageEthanol: <10 mg/dL.



Square bullet50 mg/dL: decreased inhibition, slight incoordination


Square bullet100 mg/dL: slow reaction time; altered sensory ability


Square bullet150 mg/dL: altered thought processes; personality, behavior changes


Square bullet200 mg/dL: staggering gait, nausea, vomiting, mental confusion


Square bullet300 mg/dL: slurred speech, sensory loss, visual disturbance


Square bullet400 mg/dL: hypothermia, hypoglycemia, poor muscle control, seizures


Square bullet700 mg/dL: unconsciousness, decreased reflexes, respiratory failure (may also occur at lower concentrations)


imageIsopropanol (isopropyl alcohol): <10 mg/dL (normal); toxic effects generally seen at 50–100 mg/dL.


imageMethanol: <10 mg/dL (normal); levels >25 mg/dL are generally considered toxic.


imageAcetone: <10 mg/dL; effects are said to be similar to ethanol for similar blood levels, but the anesthetic potency is greater.


imageUse


Square bulletBeverage (ethanol)


Square bulletSolvent and reagent


Square bulletVehicle in chemical and pharmaceutical industries


Square bulletAntiseptic (isopropyl alcohol)


imageLimitations


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


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


Square bulletIn many headspace gas chromatographic methods, acetonitrile coelutes with acetone, leading to a false-positive result. Acetonitrile may be a component in cosmetic nail remover.


Square bulletA 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.


ALDOSTERONE


imageDefinition


Square bulletPrimary mineralocorticoid secreted by the adrenal zona glomerulosa. The role of aldosterone in metabolism is the control of sodium and potassium. Regulating sodium ion concentration, in turn, regulates fluid volume. Aldosterone acts to decrease excretion of sodium and increase the excretion of potassium at the kidney, sweat glands, and salivary glands.


Square bulletNormal range:



image8:00–10:00 AM (sitting): 3–34 ng/dL


image8:00–10:00 AM (supine): 2–19 ng/dL


image4:00–6:00 PM (sitting): 2–23 ng/dL


imageUse


Square bulletDiagnosis of primary hyperaldosteronism


Square bulletDifferential diagnosis of fluid and electrolyte disorders


Square bulletAssessment of adrenal aldosterone production


imageInterpretation


Increased In


Square bulletPrimary aldosteronism


Square bulletSecondary aldosteronism


Square bulletBarter syndrome


Square bulletPregnancy


Square bulletVery low–sodium diet


Square bulletUrine aldosterone also increased in nephrosis


Decreased In


Square bulletHyporeninemic hypoaldosteronism (Cushing syndrome)


Square bulletCAH


Square bulletCongenital deficiency of aldosterone synthetase


Square bulletAddison disease


Square bulletVery high–sodium diet


imageLimitations


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


Square bulletLicorice may mimic aldosterone effects and should be avoided 2 weeks before the test.


ALKALINE PHOSPHATASE (ALP)


imageDefinition


Square bulletALP refers to a family of enzymes that catalyze hydrolysis of phosphate esters at an alkaline pH. There are at least five isoenzymes derived from the liver (sinusoidal and bile canalicular surface of hepatocytes), bone, intestine (brush border of mucosal cells), placenta, and tumor-associated tissues separated by electrophoresis. Placenta and tumor-associated ALP are the most heat resistant to inactivation. More than 95% of total ALP activity comes from the bone and liver (approximately 1:1 ratio). The half-life of ALP is 7–10 days.


Square bulletNormal range:



image0–1 year: 150–350 IU/L


image1–16 years: 30–300 IU/L


image>16 years: 30–115 IU/L


imageUse


Square bulletDiagnosis and treatment of the liver, bone, intestinal, and parathyroid diseases


imageInterpretation


Increased In


Square bulletIncreased bone formation


Square bulletBone diseases (metastatic carcinoma of the bone, myeloma, Paget disease)


Square bulletRenal disease (renal rickets due to vitamin D–resistant rickets associated with secondary hyperparathyroidism)


Square bulletLiver disease (e.g., infectious mononucleosis, uncomplicated extrahepatic biliary obstruction, liver abscess)


Square bulletMiscellaneous (extrahepatic sepsis, ulcerative colitis, pancreatitis, phenytoin, and alcohol use)


Square bulletBone origin—increased deposition of calcium



imageHyperparathyroidism


imagePaget 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 bone or metastatic carcinoma from the prostate.


imageIncrease in cases of metastases to bone is marked only in prostate carcinoma.


imageOsteoblastic bone tumors (osteogenic sarcoma, metastatic carcinoma).


imageOsteogenesis imperfecta (due to healing fractures).


imageFamilial osteoectasia.


imageOsteomalacia, rickets.


imagePolyostotic fibrous dysplasia.


imageOsteomyelitis.


imageLate pregnancy; reverts to normal level by 20th day postpartum.


imageChildren <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.


imageAdministration of ergosterol.


imageHyperthyroidism.


imageTransient hyperphosphatasemia of infancy


imageHodgkin disease.


imageHealing of extensive fractures (slightly).

Only gold members can continue reading. Log In or Register to continue

Stay updated, free articles. Join our Telegram channel

Nov 3, 2016 | Posted by in GENERAL & FAMILY MEDICINE | Comments Off on 16 Laboratory Tests

Full access? Get Clinical Tree

Get Clinical Tree app for offline access