Vol. 19, No. 3, July 2005
Laboratory Testing for Myasthenic and Paraneoplastic Syndromes 
Test Updates 
  Test Methodology, Reference Range, and Specimen Handling Changes
 
  • AChR Ganglionic Neuronal Antibody
  • Amiodarone and Desethylamiodarone
  • Coagulation Test Updates
  • Estimated Glomerular Filtration Rate
  • Neutrophil Oxidative Burst Assay
  • Phosphorus, Urine, 24 Hour
  • Serum Bactericidal Titer (SBT)
  • Uric Acid, Urine, 24 Hour
  • Volatiles Group by GLC
  Discontinued Test
 
  • Thyrotropin Binding Inhibitory Immunoglobulin

Laboratory Testing for Myasthenic and Paraneoplastic Syndromes

Steven Mandell, M.D., Director of MLabs Program
Kajal Sitwala, M.D., Ph.D., UM Pathology House Officer

Myasthenia Gravis and Lambert-Eaton Myasthenic syndrome (MG and LES, respectively) are frequently compared and contrasted in their clinical presentation, pathophysiology and clinical significance. They are two examples of a set of increasingly recognized syndromes associated with malignancies. They are reviewed below in an attempt to convey the role of laboratory testing in the diagnosis and follow up of paraneoplastic disorders.

Acquired myasthenia gravis (MG) is a prototypical autoimmune disorder, with the formation of IgG antibodies to the alpha-1 subunit of the acetylcholine receptor (AChR) at the neuromuscular junction (NMJ) postsynaptic membrane resulting in a reduced function of the receptor. The clinical manifestations of this disorder are characterized by weakness and fatigability of skeletal muscles.

The disease is not uncommon, occurring in 3 in 100,000 persons and, when arising before the age of 40, most commonly affects women. Heightened awareness of this condition in young, adult women helps in making the diagnosis. Transient neonatal MG also occurs due to passive acquisition of maternal antibodies. For children and infants, the differential diagnosis includes congenital MG in which patients have a hereditary defect in the acetylcholine receptor, rather than autoantibodies, to account for the disorder. For patients older than 60, the gender distribution becomes equal and the differential diagnosis may be broadened (Table 1).

TABLE 1

The differential diagnosis of myasthenic signs or symptoms

  • Myasthenia gravis
  • Congenital myasthenic syndromes
  • Lambert-Eaton myasthenic syndrome
  • Drug-induced myasthenia-like syndrome due to D-penicillamine
  • Chronic progressive external ophthalmoplegia
  • Chronic progressive external ophthalmoplegia with ragged red fiber myopathy (Kearns-Sayre syndrome/mitochondrial encephalomyopathies)
  • Brainstem disorders (stroke, sarcoidosis)
  • Amyotrophic lateral sclerosis
  • Depression
  • Neurotoxins (botulism, snake venom)
  • Multiple sclerosis
  • Hyperthyroidism
  • Chronic fatigue syndrome
  • Pernicious anemia
  • Myopathies
  • Acute Guillain-Barré (motor type)
  • Miller Fisher syndrome

Seventy-five percent of acquired MG patients have a thymic disorder, 85% of those with thymic hyperplasia and 15% with thymoma. In those with thymoma, thymectomy can result in remission of MG in 20-60% of patients and the degree of success may be surgeon, or surgical procedure type-dependent. Remission rates may be lower in those undergoing thymectomy for hyperplasia but signs and symptoms may still lessen, if not totally abate. For acquired MG patients without thymoma, those younger than 60 may still be triaged to thymectomy for the possibility of occult disease but medical therapy is the primary intervention for those older than 60. Medical therapy consists of anticholinesterase agents (mestinon) or immunosuppressive therapy (prednisone, cyclosporine or imuran), or both; plasmapheresis may be helpful for acute exacerbations.

Symptoms for the typical patient begin due to weakness in extraocular muscles, causing ptosis or diplopia and a visit to the ophthalmologist; 50% of MG patients will present with ocular complaints. Exam reveals a spectrum of extraocular muscle disorders ranging from isolated muscle palsies to total external ophthalmoplegia. Some patients may have signs or symptoms limited to the extraocular muscles (ocular MG). MRI or CT scan of the brain and orbit is essential in ocular MG to rule out masses compressing cranial nerves.

Patients without ocular symptoms typically complain of easy fatigability. Examination in these patients may reveal weakness in facial, oropharyngeal, limbal, and trunk muscles, without other signs of neurologic deficit, such as sensory loss, change in deep tendon reflexes, or muscle atrophy. Patients show incremental weakness as strength challenges are repeated.

Electrophysiologic studies confirm the decrement in motor responses with repeated stimulation while nerve conduction studies remain normal. Administration of anticholinesterase agents will improve the motor response to repeated stimulation for MG patients. (This is in distinction from Lambert-Eaton myasthenic syndrome, described below, where muscle weakness improves with continued contraction of the muscle.)

In the era before medical intervention, one third of patients suffered a grave demise (hence, “gravis”). Now, five-year survival is greater than 95% with those succumbing doing so during acute exacerbations of respiratory failure. Nearly 20% of patients may undergo a spontaneous remission after experiencing disease for a period of years.

Lambert-Eaton myasthenic syndrome (LES), should be considered in the differential diagnosis of patients presenting with weakness but LES patients rarely have ocular muscle involvement at presentation (ptosis and diplopia may occur later in the disease course and may be transient). Instead, the typical patient is a 60 year old man (male to female ratio = 7/3), with a significant smoking history, that presents with weakness in the proximal muscles of the legs and arms. In contrast to MG, tendon reflexes in LES are diminished at rest but improve after repeated stimulation. Like MG, LES develops as a result of autoantibody formation but antibodies are directed at voltage-dependent calcium channels integrated in the presynaptic neuron cell membrane, and prevent acetylcholine from being released into the NMJ. Rather than being associated with a thymic disorder, antibodies arising in LES do so in association with cancers, particularly small cell lung carcinoma (60% of LES patients have this), and occasionally lung squamous cell, breast or ovarian epithelial cancers.

The terminology for antibodies identified in LES is derived from biophysical properties of the calcium channels. Calcium [Ca(2+)] channels are multisubunit complexes with a membrane “channel” (“pore”) formed by an alpha-1 subunit, and auxiliary subunits beta, alpha-2/delta, and gamma, which regulate channel activity. There are at least 6 classes of alpha-1 subunits, derived from 6 genes representing members of a gene family. The different alpha-1 classes that make up a Ca(2+) channel differ in their biophysical and pharmacologic properties and tissue locations. Both alpha-1A and alpha-1B isoforms are expressed in neuronal tissue and correspond to the biophysical and pharmacologic properties of the P/Q and N Ca(2+) channel types, respectively. In LES, IgG binds to domains of the alpha-1A (P/Q type) isoform in nearly all patients (5-15% may lack the P/Q antibody) and N-type antibodies occur less frequently. The other isoforms of voltage-dependent Ca(2+) channels are involved in a variety of Ca(2+)-dependent processes, including muscle contraction, hormone or neurotransmitter release, and gene expression.

Investigators at Mayo Clinic have characterized the CRMP-5 (collapsing response mediator protein type 5) molecule as another target for paraneoplastic autoantibody formation. This molecule has been found in central and peripheral nervous system neurons as well as small cell carcinoma and thymoma and the presence of autoantibodies is associated with a variety of clinical presentations, including myasthenic syndromes, retinopathy and optic neuritis (Table 2).

TABLE 2

Neurological syndromes in patients with anti CRMP 5

Syndrome
%
Peripheral neuropathy
59.6
Cerebellar ataxia
51.1
Ocular involvement (optic neuritis/uveitis)
17.0
Limbic encephalitis
14.9
Myasthenic syndrome
10.6
Gastroparesia
10.6
Chorea
8.5
Dysautomia
4.3
Opsoclonus
2.1

Adapted from http://www.pnseuronet.org/professionals/antibody/cv2.html, January 11, 2005.

TABLE 3

Additional antibody-mediated paraneoplastic disorders

Antibody
Disorder
Predominant malignancy
Anti-ANNA-1 (Anti-Hu)
Sensory neuronopathy
Small cell lung cancer
Antiamphiphysin
Stiff-man syndrome
Breast, Small cell lung cancer
Anti-MAG
Sensorimotor neuropathy
Waldenstrom’s macroglobulinemia
Anti-VGKC
Neuromyotonia
Thymoma, Small cell lung cancer
Antititin
Myasthenia Gravis
Thymic epithelial tumor
Antineuronal nicotinic Ach receptor
Autonomic dysfunction and others
Several: lung, bladder, rectum, thyroid

ANNA-1 = anti-neuronal nuclear type 1; MAG = myelin associated glycoprotein; VGKC = voltage-gated potassium channel.

 

The clinical and laboratory identification of paraneoplastic syndromes is widening as new antibodies and their targets are characterized (Table 3). A heightened awareness of these syndromes in those with malignancy is critical to making the diagnosis. As with MG, LES and CRMP-5, variations in the tissue distribution of targets of paraneoplastic antibodies will result in different clinical presentations, with most recognized due to their peripheral or central nervous system manifestations (Table 4).

TABLE 4

Paraneoplastic syndromes of the nervous system

Peripheral Nervous System

  • Paraneoplastic sensorimotor neuropathy
  • Paraneoplastic vasculitis of nerve and muscle
  • Peripheral neuropathy associated with malignant monoclonal gammopathies (e.g., P.O.E.M.S.)
  • Paraneoplastic peripheral nerve hyperexcitability (PNH) associated with autoantibodies to voltage-gated potassium channels
  • Paraneoplastic autonomic dysfunction
  • Lambert-Eaton myasthenic syndrome
  • Myasthenia Gravis (MG)
  • Polymyositis and Dermatomyositis (PM/DM)
  • Acute necrotizing myopathy

Central Nervous System

  • Paraneoplastic sensory neuronopathy (PSN)
  • Paraneoplastic encephalomyelitis (PEM)

Adapted from Dalmau (see references)

The laboratory evaluation of patients with myasthenic syndromes may be useful for several reasons:

  1. To confirm a diagnosis of myasthenia gravis
  2. To indicate the presence of a thymoma or thymoma marker
  3. To determine whether thymectomy may not be indicated in a subset of patients (MuSK Ab positive – see text below)
  4. To monitor effects of therapy in myasthenic patients
  5. To separate congenital from acquired myasthenia in the young
  6. To help confirm Lambert-Eaton myasthenic syndrome (LES)
  7. To exclude other autoimmune diseases that may occur in association with MG (rheumatoid arthritis, hyperthyroidism, Grave’s disease and lupus erythematosus).
  8. To identify other paraneoplastic syndromes that may mimic MG, LES, or other diseases.

MLabs, via Mayo Medical Laboratories, provides diagnostic panels for the subclassification of myasthenic syndromes (Table 5), or follow up panels for patients already diagnosed with MG (Table 6).

Muscle AChR binding antibodies comprise the first order assay. They are not found in congenital forms of MG and are very uncommon in neurologic conditions other than acquired MG (they may be present with autoimmune liver disease but this is separated from MG clinically). Binding antibodies are useful for detecting subclinical MG in patients with thymoma, graft versus host disease or D-penicillamine patients with signs or symptoms of drug-induced MG. These antibodies may be negative in the first year of MG symptoms (90-100% sensitivity) and for diagnostic panels, the additional search for AChR modulating antibodies, with or without blocking antibodies, increases the screen sensitivity to nearly 100%. The addition of blocking antibodies is also helpful in separating patients with MG from those with a false positive due to autoimmune hepatitis (specificity nearly 100%; see Table 7.).

TABLE 5

Antibody panels in the evaluation of myasthenic syndromes

 

Lab Test Cascade for Myasthenic Syndromes

Antibody Type

Pediatric MG vs. Congenital

Adult Evaluation MG / Thymoma

MG vs. LES Evaluation

Muscle AChR binding *

X

X

X

Muscle AChR modulating

X

X

X

Muscle AChR blocking

R

R

R

Muscle striational *

 

X

X

CRMP-5-IgG Western

 

X

R

AChR Ganglionic Neuronal Antibody

 

X

R

Ca channel binding N-type

 

 

X

Ca channel binding P/Q-type

 

 

X

MML Test Code

83371

83372

83369

MML Test Panel Name

Myasthenia Gravis Evaluation, Pediatric

Myasthenia Gravis Evaluation, Thymoma

Myasthenia Gravis / Lambert-Eaton Syndrome Evaluation

“*” = test available as a separate orderable; “X” = tests routinely part of evaluation; “R” = tests performed reflexively, if antibody in line above is found to be absent. MG/LES Evaluation: if AChR modulating antibody is >=90% and striational antibody is >=1:60, CRMP-5-IgG Western Blot and AChR Ganglionic Neuronal Antibody will be performed.


TABLE 6

Quantitative analysis for follow up of MG patients

Antibody Type

MG only

MG with Thymoma if mod/block present

MG with Thymoma if mod/block absent

Muscle AChR binding

X

X

X

Muscle AChR modulating

X

X

 

Muscle AChR blocking

X

X

 

Muscle striational

 

X

X

 

TABLE 7

Incidence of myasthenic autoantibodies in disease states

Antibody Type

Ocular Limited MG

MG

Thymoma

LES/LES Neoplastic

Neoplastic* Encephalomyelo-neuropathies

Autoimmune Liver Disease

BMT with GVHD

Rheumatoid Arthritis with Penicillamine Rx

Muscle AChR binding

71%

90%

~100%

5-10%

5-10%

30%

 

 

Muscle AChR modulationg

 

10%

90%

 

 

 

 

 

Muscle AChR blocking

30%

52%

 

 

 

 

 

 

Muscle striational

 

30%

80%

3-5%

5-10%

25%

25%

3-5%

CRMP-5-IgG Western

 

 

13%

4%/60%

 

 

 

 

Ca channel binding N-type

 

 

Rare

49%/73%

27%

 

 

 

Ca channel binding P/Q-type

 

<3%

Rare

95%/100%

20%

 

 

 

  1. Muscle AChR may be absent in 1st year of MG onset
  2. Muscle striational incidence increases with age; marker of thymoma recurrence
  3. The combination of Binding Ab and Modulating Ab gives close to 100% sensitivity for MG
  4. Although Binding and Modulation Abs can be seen in LES, the addition of Ca Channel Abs results in over 95% specificity for distinguishing MG from LES
  5. Other conditions with + Binding Ab, such as autoimmune liver disease, do not cause symptoms that are likely to be confused with MG. However, a positive Blocking Ab brings specificity close to 100%
  6. Addition of Striational Ab increases sensitivity even further in elderly patients. More importantly, it raises the index of suspicion for thymoma.

Muscle AChR modulating and blocking antibodies may be performed simultaneously in a second order assay. They are useful for confirming the separation of acquired and congenital MG and the blocking antibodies form a third order test in the evaluation of polyclonal versus clonal (neoplastic/paraneoplastic) antibody formation. Blocking antibody quantification may also be helpful in monitoring disease course.

TABLE 8

Paraneoplastic autoantibody panel

Antibody Name

 

Muscle AChR binding

X

Muscle AChR modulating

R

Muscle AChR blocking

R

Muscle striational

X

Collapsin Response-Mediator Protein-5 (CRMP-5)-IgG

X

CRMP-5-IgG Western Blot

R

Ca channel binding N-type

X

Ca channel binding P/Q-type

X

Amphiphysin

X

Anti-neuronal nuclear type 1

X

Anti-neuronal nuclear type 2

X

Anti-neuronal nuclear type 3

X

Purkinje Cell Cytoplasmic Antibody Type 1

X

Purkinje Cell Cytoplasmic Antibody Type 2

X

Purkinje Cell Cytoplasmic Antibody Type Tr

X

AChR Ganglionic Neuronal Antibody

X

“X” = included in panel; “R” = reflexively tested for if test “X” immediately above in the panel is not identified or indeterminate. If immunofluorescence assay for CRMP-5-IgG is indeterminate or positive, CRMP-5-IgG Western blot is performed. If calcium channel P/Q-Type or N-Type is >20, paraneoplastic auto-antibody Western blot and CRMP-5-IgG Western blot are performed. If ACh receptor binding antibody is >0.02 or if striational antibodies is >= 1:60, ACh receptor modulating antibodies, paraneoplastic autoantibody Western blot, and CRMP-5-IgG Western blot are performed. If ACh receptor modulating antibodies antibody is >= 40% loss, ACh receptor blocking antibodies radioimmunoassay is performed. CRMP-5-IgG Western blot is also performed by specific request for more sensitive detection of CRMP-5-IgG.

The addition of antibodies against striated muscle (striational antibodies) increases the sensitivity of screening tests particularly in rare elderly patients who may have a delayed appearance or absence of binding antibody. Striational antibodies are present in

30% of adult MG patients but may be present in 80% of those with thymoma. This marker becomes useful therefore in serial analysis as it may indicate recurrence of thymoma after surgery. Serial striational antibody evaluation may also be helpful in evaluating the response to therapy for drug-induced MG or graft versus host disease.

Rarely, patients presenting with acquired MG may lack AChR antibodies. In 50-70% of these, antibodies to muscle specific tyrosine kinase (MuSK) may be identified as an etiology. MuSK antibodies have not been identified in pure ocular MG, but have been associated with increased presence of oculobulbar muscle weakness as well as increased frequency of respiratory crises, even while on immunosuppression. Patients with this antibody profile maintain a female preponderance (80%), tend to be younger than the typical acquired MG patient, and have an increased incidence in Afro-Americans. Thymectomy has not been found to be effective in abating symptoms in this subset and most patients will not benefit from anticholinesterase agents (e.g., pyridostigmine). MuSK Antibody Testing is made available at MLabs via our relationship with Athena Diagnostics (test code #470).

In patients with subacute basal ganglionic disorders (chorea, Parkinsonism), cranial neuropathies (especially loss of vision, taste or smell) and myelopathies, an extended panel for paraneoplastic disorders is indicated (Table 8).

Excellent, comprehensive outlines of neuromuscular disorders can be found at http://www.neuro.wustl.edu/neuromuscular/index.html, a web page maintained by Dr. Alan Pestronk at the Neuromuscular Disease Center at Washington University, St. Louis, Missouri, and at http://neuroland.com/default_old.htm , a website maintained by Charles Tuen, M.D., a Neurologist at Methodist Medical Center in Dallas, Texas. 

References

  1. Glass DJ, Yancopoulos GD. Sequential roles of agrin, MuSK and rapsyn during neuromuscular junction formation. Curr Opin Neurobiol. 1997 Jun;7(3):379-84. Review.
  2. Liyanage Y, Hoch W, Beeson, D, Vincent A. The agrin/muscle-specific kinase pathway: new targets for autoimmune and genetic disorders at the neuromuscular junction. Muscle Nerve. 2002 Jan;25(1):4-16. Review.
  3. Pestronk A, The Neuromuscular Disease Center: www.neuro.wustl.edu/neuromuscular. Neuromuscular Disease Center , Washington University, June 3, 2005.
  4. “CALCIUM CHANNEL, VOLTAGE-DEPENDENT, P/Q TYPE, ALPHA-1A SUBUNIT; CACNA1A” from Online Mendelian Inheritance in Mankind maintained by Johns Hopkins University , http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=601011, June 3, 2005.
  5. Vernino S, Lennon VA. Autoantibody profiles and neurological correlations of thymoma. Clin Cancer Res. 2004 Nov 1;10(21):7270-5.
  6. Awwad S , Ma’luf R, Hamush N. Myasthenia Gravis. February 14, 2005 . http://www.emedicine.com/oph/topic263.htm.
  7. Kumar V, Abba AK , Nelson F, eds. Pathologic Basis of Disease, 7 th edition. Elsevier Inc, 2005. pp 1344-1345.
  8. Tuen C, “Myasthenia Gravis: Information for healthcare workers.” http://neuroland.com/nm/myas_gra.htm , June 3, 2005.
  9. ”Common Questions Patients Ask About Thymectomy for Myasthenia Gravis.” February 10, 2003, http://www.myasthenia.org/information/thymectomy.htm, Myasthenia Gravis Foundation of America, Inc.
  10. Cross SA, Salomao DR, Parisi JE, Kryzer TJ, Bradley EA, Mines JA, Lam BL, Lennon VA. Paraneoplastic autoimmune optic neuritis with retinitis defined by CRMP-5-IgG. Ann Neurol. 2003 Jul;54(1):38-50.
  11. Yu Z, Kryzer TJ, Griesmann GE, Kim K, Benarroch EE, Lennon VA. CRMP-5 neuronal autoantibody: marker of lung cancer and thymoma-related autoimmunity. Ann Neurol. 2001 Feb;49(2):146-54.
  12. Dalmau J. Paraneoplastic syndromes of the peripheral nervous system. http://neuropathymd.org/topical/28/Paraneoplastic%20Neuropathies.pdf.
  13. Lennon V, Kryzer T, Griesman G, O’Suilleabhain P, Windebank A, Woppman A, Milianich G and Lambert E. Calcium-Channel Antibodies in the Lambert–Eaton Syndrome and Other Paraneoplastic Syndromes. NEJM Vol 332:1467-1475, No.22, June 1, 1995.

Copyright © 2005
University of Michigan Medical School


Test Updates

Test Methodology, Reference Range, and Specimen Handling Changes

AChR Ganglionic Neuronal Antibody

Effective May 5, 2005, Mayo Medical Laboratories implemented a new test, AChR Ganglionic Neuronal Antibody. This test is not orderable individually, but is available as part of the following profiles:

Myasthenia Gravis Evaluation, Adult : If AChR Modulating Antibody is >=90% and Striational Antibody is >=1:60, AChR Ganglionic Neuronal Antibody and CRMP-5-IgG Western blot will be performed at an additional charge.

Myasthenia Gravis Evaluation, Thyoma : AChR Ganglionic Neuronal Antibody is included as a component of this profile.

Myasthenia Gravis / Lambert-Eaton Syndrome Evaluation : If AChR Modulating Antibody is >=90% and Striational Antibody is >=1:60, AChR Ganglionic Neuronal Antibody and CRMP-5-IgG Western blot will be performed at an additional charge.

Paraneoplastic Autoantibody Evaluation : AChR Ganglionic Neuronal Antibody is included as a component of this profile.

Amiodarone and Desethylamiodarone

Effective March 22, 2005 , the MLabs Drug Analysis and Toxicology Laboratory has discontinued the Amoidarone and Desethylamiodarone assay. This test is referred to Mayo Medical Laboratories:

Collection Instructions : Collect blood in a red or lavender top tube; do not use SST tube. Centrifuge, aliquot 3 mL (minimum 1.1 mL) of serum or plasma into a plastic vial and freeze. Draw peak levels 2 hours after dose, trough immediately before next dose.

Reference Range : Amiodarone: Therapeutic: 1.5 – 2.5 µg/mL, Toxic: greater than 3.5 µg/mL; Desethylamiodarone: Therapeutic: 1.5 – 2.5 µg/mL, Toxic: greater than 3.5 µg/mL.

Coagulation Test Updates

Anti-IIa Inhibitor Assay

Therapeutic ranges have been added:

Reference Range : The concentration in a normal individual is zero. The therapeutic range for argatroban is 0.4 - 1.2 µg/mL. The therapeutic range for hirudin is 2 - 4 µg/mL.

Coagulation Factor Xa Inhibition

Effective May 4, 2005 , the Charting Name changed from “HEPARIN-ANTI Xa” to “LMWH Anti-Xa”, the test name was changed to Coagulation Anti-Xa, LMWH in the MLabs Handbook, and the therapeutic range has been added:

Reference Range : The anti-factor Xa level in a normal individual is less than 0.05 units/mL. The therapeutic range is 0.6 - 1.0 units/mL. Critical value: > or = 1.5 units/mL.

Heparin, Unfractionated

Effective May 4, 2005 , the Charting Name changed from “HEPARIN” to “UFH Anti-Xa”, the test name was changed to Coagulation Anti-Xa, UFH in the MLabs Handbook, and the therapeutic range has been added:

Reference Range : The heparin activity in a normal individual is zero. The therapeutic range with this technique is 0.3 - 0.7 units/mL. Critical value: > or = 1.5 units/mL.

Inhibitor Screen

Effective May 4, 2005 , the interpretive comment reported with the test result has been changed to read as follows: “If the patient is being treated with heparin, low molecular weight heparin, fondaparinux, coumadin, or a direct thrombin inhibitor, the result of the inhibitor screen cannot be evaluated. All these agents will give "inhibitor" results. Reorder the Inhibitor Screen two weeks after coumadin is discontinued or 72 hours after the heparins or thrombin inhibitors are discontinued.”

PTT (Activated Partial Thromboplastin Time)

Effective May 4, 2005 , the therapeutic range if the aPTT is being used to monitor heparin has been added:

Reference Range : Approximately 20 - 30 seconds. If the aPTT is being used to monitor heparin, the therapeutic range is approximately 50 - 80 seconds. Please refer to patient report or contact MLabs for current reference ranges. Critical value: greater than 3 times upper limit of normal.

Estimated Glomerular Filtration Rate

Beginning Tuesday, May 3rd, 2005 , Estimated Glomerular Filtration Rate (EGFR) is no longer a component of the Renal Function Panel. Instead, EGFR is associated with creatinine requests in patients 20 yrs of age and older. Every time a creatinine is ordered on an outpatient or client specimen, either alone or as part of a panel, the EGFR values for both an African American and a Non-African American individual will be calculated and reported. For ESA patients, inpatients and clients, an EGFR will be included only once every 7 days. Creatinine is included with the following profiles: Basic Metabolic Panel, Comprehensive Metabolic Panel, Renal Function Panel, and Creatinine Clearance.

Reference Range : The EGFR will be reported in mL/min calculated using the MDRD study equation. No change has been made to the MDRD calculation. The report will include sex specific ranges; there will no longer be age dependent ranges. All eGRF results less than 60 mL/min will be flagged as low.

The following interpretation will appear with every eGFR: "The MDRD formula for estimation of GFR (eGFR) was developed in a population of adults (>19 years old) with slowly-declining or stable reduced kidney function. The MDRD formula should not be used to predict eGFR in unstable patients or in children. A GFR estimate between 15 and 59 mL/min for >= 3 months is classified as chronic kidney disease (Stage 3 or 4)."

If the patient is greater than 70 yrs of age, an additional comment will appear: "The MDRD formula used to calculate the eGFR result has not been validated in patients > 70 years of age."

The Glomerular Filtration Rate (GFR) is usually accepted as the best overall index of kidney function in health and disease. Since GFR cannot be measured directly, the National Kidney Disease Education Program (NKDEP) of the National Institute of Diabetes and Diseases of the Kidney (NIDDK), National Kidney Foundation (NKF) and American Society of Nephrology (ASN) recommend estimating GFR from serum creatinine using the MDRD (Modification of Diet in Renal Disease) Study equation. This equation uses serum creatinine in combination with age, sex and race to estimate GFR and therefore improves upon several of the limitations with the use of serum creatinine. The MDRD Study equation has been rigorously developed and validated, and is more accurate than measured creatinine clearance from a 24-hour urine collection. More information about GFR estimates is available on the National Kidney Foundation website: http://www.kidney.org.

Neutrophil Oxidative Burst Assay

Effective April 11, 2005 , the Neutrophil Oxidative Burst assay is referred to Mayo Medical Laboratories.

Collection Instructions : Collect specimen in a green top tube. Also collect a normal control specimen in a green top tube (NOT from a family member) at the same time that the patient is drawn. Send 5 mL (minimum 1 mL) intact whole blood stored and transported at room temperature within 24 hours of collection; do not refrigerate or freeze.

Reference Range : Absent oxidative burst is consistent with CGD. Carriers have 2 neutrophil populations: 1 population will have a normal oxidative burst and the second will demonstrate no oxidative burst.

Phosphorus, Urine, 24 Hour

Effective May 31, 2005 , the following reference range has been added to 24 hour urine phosphorus testing: 400 – 1200 mg/TV.

Serum Bactericidal Titer

Effective April 1, 2005 , the MLabs Microbiology Laboratory discontinued performing the Serum Bactericidal Titer assay. This test is referred to Mayo Medical Laboratories.

Collection Instructions : Both infecting bacteria and serum are required for this test. Bacteria should be in pure culture, actively growing, placed in a proper mailing container (agar plates are not acceptable), and labeled as an etiologic agent. Keep at room temperature; do not refrigerate or freeze. If culture was done by MLabs, contact the MLabs Client Services Center within 7 days of initial culture date to request that the patient's isolate be saved for SBT testing. Collect PEAK blood specimen, 30 minutes post I.V., 1 hr post I.M., or 1-2 hr post-oral dose, in red top or SST tube. Centrifuge, aliquot 3 mL (minimum 2 mL) of serum into a plastic vial and freeze. Indicate organism identification, antibiotic(s), route of administration, specimen source, and collection date/time.

Reference Range : Titer of > or =99.9% killing will be reported . High SBTs (at least > or =1:8 and preferably > or =1:64) provide in vitro evidence that the specimen tested is bactericidal against the organism tested. It is important to remember that the SBT measures the combined activity of all antimicrobial agents present at the time of serum collection.

Uric Acid, Urine, 24 Hour

Effective May 31, 2005 , the following reference range has been added to 24 hour uric acid testing: 250 - 750 mg/TV (with average diet).

Volatiles Group by GLC

Beginning April 28, 2005 , Acetone (ACET) has been added as a component of the Volatiles Group by GLC assay. Other components of the volatile screen are Ethanol, Methanol, Isopropanol, and Ethylene Glycol. The acetone analysis has always been performed, but reported as a comment if present. The Acetone level will not be orderable as an individual test.

The critical level for acetone is 20 mg/dL. The following interpretive comment will accompany the result: "Acetone is a metabolite of isopropanol and may be elevated in cases of acute isopropanol ingestion. In diabetic ketoacidosis acetone can also be found in serum concentrations up to 70 mg/dL".

Discontinued Test

Thyrotropin Binding Inhibitory Immunoglobulin

Effective May 24, 2005 , Mayo Medical Laboratories test # 90180, Thyrotropin Binding Inhibitory Immunoglobulin, referred to Quest Diagnostics, Inc., has become obsolete. The recommended replacement is the Thyrotropin Receptor Antibody assay.

For additional clarification concerning any of the information contained in this Spectrum, please contact the MLabs Client Services Center at 734-936-2598 (local), 800-862-7284 (Michigan), or 800-537-7284 (outside Michigan).
Address correspondence to: MLabs Spectrum
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Ann Arbor, MI 48106-0976
 
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This page was last updated July 13, 2005.

 

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