LABHORIZONS. New Procedures A NEWSLETTER FOR CLIENTS

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1 LABHORIZONS A NEWSLETTER FOR CLIENTS Volume XVII, No. 7 July 2017 New Procedures 5 HIAA, Plasma CPT Synonyms 5-hydroxyindoleacetic acid Use Plasma 5-hydroxy-indoleacetic acid (5HIAA or 5-HIAA) is a metabolite of serotonin that can be elevated as a result of carcinoid tumors/carcinoid syndrome. Limitations This test was developed, and its performance characteristics determined, by LabCorp. It has not been cleared or approved by the US Food and Drug Administration. Methodology High-pressure liquid chromatography (HPLC)/tandem mass spectrometry Specimen Plasma (preferred) or serum, frozen Volume 1.0 ml Minimum Volume 0.3 ml Container Green-top (heparin) tube, lavender-top (EDTA) tube, or red-top tube Patient Preparation Avoid bananas, avocados, plums, eggplant, tomatoes, plantain, pineapple, walnuts, and interfering drugs for a 72-hour period prior to and during collection. Storage Instructions Freeze. Stability Temperature Room temperature Refrigerated Frozen Freeze/thaw cycles Causes for Rejection Gross hemolysis Period 14 days 3 days 14 days stable x6 Immunoglobulin G, Monitoring of Primary Immunodeficiency Treatment Profile CPT 82784; 82787(x4) Synonyms IgG Subclasses; IgG 1,2,3,4 ; Intravenous Immunoglobulin Treatment Monitoring; Primary Immunodeficiency Treatment Monitoring Test Includes Quantitation of IgG 1, IgG 2, IgG 3, IgG 4, total IgG Use Monitoring the treatment of patients with intravenous IgG infusions who exhibit primary immunodeficiency with recurrent infections Limitations This procedure is not suitable for the measurement of samples containing rheumatoid factor, paraproteins, other circulating immune complexes (CICs), or for lipemic or hemolyzed samples due to the unpredictable degree of non-specific light scatter these sample types may generate. The results obtained from measuring IgG subclasses should not be used in assessing atopy in allergic patients. Methodology Immunologic Reference Interval Total IgG trough level: >800 mg/dl Note: Maintaining trough levels of total IgG above 800 mg/dl is reported to prevent serious bacterial illness, enteroviral meningoencephalitis, and pneumonia, but target trough levels may vary with individual patient. 1-3 Approximate targets for trough levels for IgG subclasses (mg/dl) 4 : IgG 1 IgG 2 IgG 3 IgG 4 >480 >256 >32 >32 Additional Information In the past decades, administration of exogenous pooled human immunoglobulin for intravenous use (IVIG) has become an important therapy in clinical practice. Maintaining higher trough levels (>800 mg/dl of total IgG) in order to protect patients from recurrent infections have been reported. 1-3 Percentages of relative abundance of human IgG subclasses for total IgG are reported to be approximately 60% for IgG 1, 32% for IgG 2, 4% for IgG 3, and 4% for IgG 4. 4 Specimen Serum Volume 3 ml Minimum Volume 1.8 ml Container Red-top tube or gel-barrier tube Collection Transfer serum to a plastic transport tube. Storage Instructions Refrigerate Stability Temperature Room temperature Refrigerated Frozen Freeze/thaw cycles Period 3 days 7 days 13 days stable x3 Causes for Rejection Gross lipemia; hemolysis Special Instructions State patient s age on the test request form. Footnotes 1. Orange JS, Hossny EM, Weiler CR, et al. Use of Intravenous Immunoglobulin in Human Disease: A Review of Evidence of Members of the Primary Immunodeficiency Committee of the American Academy of Allergy, Asthma, and Immunology. J Allergy Clin Immunol 2006 Apr; 117:S PubMed Orange JS, Grossman WJ, Navickis RJ, Wilkes MM. Impact of Trough IgG on Pneumonia Incidence in Primary Immunodeficiency: A Meta-analysis of Clinical Studies. Clin Immunol 2010 Oct; 137(1): PubMed Bonagura VR, Marchlewski R, Cox A, Rosenthal DW. Biologic IgG Level in Primary Immunodeficiency Disease: The IgG Level That Protects Against Recurrent Infection. J Allergy Clin Immunol 2008 Jul; 122(1): PubMed Vidarsson G, Dekkers G, Rispens T. IgG Subclasses and Allotypes: from structure to effector functions. Front Immunol Oct; 5:520. PubMed These new/revised publications are now available: ADAMTS13 Activity service announcement (L17163) Familial Hypercholesterolemia LABupdate (L17194) Cascade Testing Options brochure (L16633) Please ask your LabCorp service representative for these titles.

2 Substance Abuse Monitoring and Rehabilitation Profile, Urine (Screen With Confirmation) CPT Test Includes Amphetamines; Barbiturate; Benzodiazepines; Cannabinoid; Cocaine (Metab.); Opiates; 6-Acetylmorphine; Oxycodone/Oxymorphone; EDDP; Adulteration (Dilution) Methodology Initial testing by immunoassay; confirmation of positives by mass spectrometry Specimen Urine Volume 50 ml Container Urine container Storage Instructions Maintain specimen at room temperature. Stability: If arrival will extend beyond 7 days, then refrigerate. Special Instructions This panel is designed for substance abuse treatment programs. It is not intended for workplace testing and does not comply with regulatory workplace testing programs. Note: Test set-up allows for preliminary results to print. Special notice Revised CMS Advance Beneficiary Notice of Noncoverage (ABN) for Medicare Beneficiaries The latest version of the ABN released by the Centers for Medicare & Medicaid Services (CMS) went into effect on June 21, This version replaced the 03/11 version. LabCorp has transitioned to the latest ABN version with expiration date 03/2020. CMS announced in March 2017 that ABNs with the release date of 03/11 and issued on or after June 21, 2017, will be considered invalid. There were no changes to the form itself; however, the form now incorporates an expiration date of 03/2020 and language was added to inform beneficiaries of their rights to CMS nondiscrimination practices and how to request an ABN in an alternative format. LabCorp connectivity products have been updated to generate an ABN that reflects these revisions. For clients who do not use LabCorp s connectivity products, the latest version of the paper copy ABN has been printed and distributed through routine channels. Clients should discard paper copy ABNs with the 03/11 date and contact their local representative if they have not yet received a supply of the revised ABN. For more information about ABN, visit the ABN section of the CMS website: Updates to the Directory of Services and Interpretive Guide (DoS) α-thalassemia, DNA Analysis Synonyms Alpha-Thal Limitations This test is designed to detect copy-number changes in the α-globin gene cluster (deletions and duplications) of 28 different sequences in the HBA region. In addition, the assay detects the presence of the Constant Spring (Hb CS) mutation. Other point mutations, and variants in other genes, will not be detected by this assay. Molecular-based testing is highly accurate, but as in any laboratory test, rare diagnostic errors may occur. Results of this test are labeled for research purposes only by the assay s manufacturer. The performance characteristics of this assay have not been established by the manufacturer. The result should not be used for treatment or for diagnostic purposes without confirmation of the diagnosis by another medically established diagnostic product or procedure. The performance characteristics were determined by LabCorp. Additional Information α-thalassemia (OMIM ) is the most common inherited disorder of hemoglobin (Hb) synthesis in the world, with gene frequencies varying between 1% and 98% throughout the tropics and subtropics. α-thalassemia can occur in all ethnic groups but is more common in those of Southeast Asian descent. The American College of Obstetricians and Gynecologists recommends hemoglobinopathy screening for those of African, Southeast Asian, and Mediterranean descent. More than 95% of recognized α-thalassemia involves deletion of one or both α-globin genes from chromosome 16p13.3. DNA analysis of the α-globin region (HBA1/HBA2, OMIM /141850, 16pter-16p13.3) is performed by targeting 28 different sequences using multiplex ligation-dependent probe amplification (MLPA). This methodology detects genomic deletions and duplications involving this locus, including the seven most common types of α-thalassemia deletions (α-3.7, α-4.2, SEA, MED, THAI, FIL, and α-(20.5)), as well the Constant Spring point mutation. DNA analysis of the common α-globin gene deletions performed by multiplex polymerase chain reaction (PCR) followed by agarose gel electrophoresis may, on occasion, be used for confirmatory purposes. 2

3 ADAMTS13 Activity Limitations This test was developed, and its performance characteristics determined, by LabCorp. It has not been cleared or approved by the US Food and Drug Administration. Methodology In LabCorp s liquid chromatography tandem mass spectrometry (LC/MS-MS) assay, ADAMTS13 activity is determined by measuring the cleavage of a synthetic polypeptide substrate (referred to as vwf73) added to plasma samples. 23 The amino acid sequence of vwf73 corresponds to amino acid residues 1596 through 1668 of mature von Willebrand Factor (vwf) and, thereby, possesses the tyrosine methionine cleavage site and exosite necessary to undergo specific cleavage by plasma ADAMTS Using LC/MS-MS, cleavage of vwf73 is determined directly by measuring a specific proteolytic product of vwf73 whose quantity is directly proportional to the activity of ADAMTS13 in plasma. The LC/MS-MS activity assay is traceable to the WHO 1st International Standard for ADAMTS13 25 to ensure accurate measurements and offers several advantages relative to comparable fluorescence based assays. Collection (added the following statement and weblink) Please see Shipping Procedures for Priority ADAMTS13 Activity for information on direct shipping procedures. Footnotes (added) 23. Kokame K, Matsumoto M, Fujimura Y, Miyata T. VWF73, a region from D1596 to R1668 of von Willebrand factor, provides a minimal substrate for ADAMTS 13. Blood Jan 15;103(2): PubMed Crawley JT, de Groot R, Xiang Y, Luken BM, Lane DA. Unraveling the scissile bond: how ADAMTS13 recognizes and cleaves von Willebrand factor. Blood Sep 22;118(12): PubMed Hubbard AR, Heath AB, Kremer Hovinga JA, Subcommittee on von Willebrand Factor. Establishment of the WHO 1st International Standard ADAMTS13, plasma (12/252): communication from the SSC of the ISTH. J Thromb Haemost Jun;13(6): PubMed ADAMTS13 Activity Reflex Profile Limitations This test was developed, and its performance characteristics determined, by LabCorp. It has not been cleared or approved by the US Food and Drug Administration. Methodology In LabCorp s liquid chromatography tandem mass spectrometry (LC/MS-MS) assay, ADAMTS13 activity is determined by measuring the cleavage of a synthetic polypeptide substrate (referred to as vwf73) added to plasma samples. 23 The amino acid sequence of vwf73 corresponds to amino acid residues 1596 through 1668 of mature von Willebrand Factor (vwf) and, thereby, possesses the tyrosine methionine cleavage site and exosite necessary to undergo specific cleavage by plasma ADAMTS Using LC/MS-MS, cleavage of vwf73 is determined directly by measuring a specific proteolytic product of vwf73 whose quantity is directly proportional to the activity of ADAMTS13 in plasma. The LC/MS-MS activity assay is traceable to the WHO 1st International Standard for ADAMTS13 25 to ensure accurate measurements and offers several advantages relative to comparable fluorescence based assays. Footnotes (added) 23. Kokame K, Matsumoto M, Fujimura Y, Miyata T. VWF73, a region from D1596 to R1668 of von Willebrand factor, provides a minimal substrate for ADAMTS 13. Blood Jan 15;103(2): PubMed Crawley JT, de Groot R, Xiang Y, Luken BM, Lane DA. Unraveling the scissile bond: how ADAMTS13 recognizes and cleaves von Willebrand factor. Blood Sep 22;118(12): PubMed Hubbard AR, Heath AB, Kremer Hovinga JA, Subcommittee on von Willebrand Factor. Establishment of the WHO 1st International Standard ADAMTS13, plasma (12/252): communication from the SSC of the ISTH. J Thromb Haemost Jun;13(6): PubMed Chronic Lymphocytic Leukemia (CLL) Profile, FISH Container Green-top (sodium heparin) tube, pediatric Vacutainer is optimal; or lavender-top (EDTA) tube GJB2 Sequencing, Family-targeted (Single Exon Sequencing Known Mutation) Test Includes This test only covers the exon or amplicon that harbors the variant(s) of interest. Other regions of the gene will not be examined. Use Detects known familial mutations in the connexin 26 (GJB2) gene associated with nonsyndromic sensorineural hearing loss (NSHL). This option is available when the mutation is known and can be documented by the ordering physician. If the mutation cannot be documented, please order full gene sequencing. Limitations This method does not reliably detect mosaic variants; large deletions; large duplications, inversions, or other rearrangements; deep intronic variants or variants outside of the regions targeted by this analysis. It may be affected by allele-dropout, it may not allow determination of the exact numbers of T/A or microsatellite repeats, and it does not allow any conclusion as to whether two heterozygous variants are present on the same or on different chromosome copies. Additional Information Connexin 26 is one of the most significant genes involved in congenital, nonsyndromic, sensorineural hearing loss (NSHL, OMIM ) (GJB2, OMIM ). Connexin 26 produces a protein that directs the intracellular transfer of ions and molecules that are important in hearing. GJB2 is associated with both autosomal recessive (DFNB1) and autosomal dominant (DFNA3) hearing loss. GJB2 Sequencing, Full Gene Sequencing Test Includes Detects mutations in the coding region and noncoding first exon of the (GJB2) gene, plus at least two and typically 20 flanking intronic nucleotides upstream and downstream of each coding exon, covering the conserved donor and acceptor splice sites. Use Confirms a diagnosis of GJB2-related nonsyndromic sensioneural hearing loss; detects carriers. Limitations This method does not reliably detect mosaic variants; large deletions; large duplications, inversions, or other rearrangements; deep intronic variants or variants outside of the regions targeted by this analysis. It may be affected by allele-dropout, it may not allow determination of the exact numbers of T/A or microsatellite repeats, and it does not allow any conclusion as to whether two heterozygous variants are present on the same or on different chromosome copies. Additional Information Connexin 26 is one of the most significant genes involved in congenital, nonsyndromic, sensorineural hearing loss (NSHL, OMIM ) (GJB2, OMIM ). Connexin 26 produces a protein that directs the intracellular transfer of ions and molecules that are important in hearing. GJB2 is associated with both autosomal recessive (DFNB1) and autosomal dominant (DFNA3) hearing loss. Helicobacter pylori Urea Breath Test Synonyms (Removed BreathTek UBT) 3

4 Inheritest Ashkenazi Jewish Carrier Screening Panel, NGS Test Includes Screening for 39 genes, including fragile X carrier screening and spinal muscular atrophy (SMA) carrier screening. This test includes: ABCC8, ASPA, ATP7B, BCKDHA, BCKDHB, BLM, CFTR, CLRN1, DHCR7, DLD, FAH, FANCC, FKTN, G6PC, GALT, GBA, HEXA, IKBKAP, MCOLN1, NEB, PCDH15, PKHD1, PMM2, SMPD1, TMEM216, ADAMTS2, BBS2, COL4A3, CPT2, DHDDS, FMR1, MPL, MTTP, PEX2, PHGDH, RTEL1, SLC35A3, SMN1 and SUMF1. Inheritest Comprehensive Panel, NGS Test Includes Screening for 142 genes, including fragile X carrier screening and spinal muscular atrophy (SMA) carrier screening. This test includes: ABCC8, ACADM, ADA, AGA, AGL, AGXT, ALDH3A2, ALDOB, ARSA, ASL, ASPA, ASS1, ATM, ATP7B, BBS1, BBS10, BCKDHA, BCKDHB, BCS1L, BLM, CBS, CFTR, CLN3, CLN5, CLN8, CLRN1, CTNS, DHCR7, DLD, DPYD, ETHE1, FAH, FANCC, FKTN, G6PC, GAA, GALC, GALT, GBA, GCDH, GLDC, GRHPR, GSS, HADHA, HBB, HEXA, HEXB, HLCS, HMGCL, HSD17B4, IDUA, IKBKAP, LAMA3, LAMB3, LAMC2, LRPPRC, MAN2B1, MCOLN1, MEFV, MMAA, MMAB, MMACHC, MUT, NBN, NEB, NPC1, NPC2, NPHS1, NPHS2, PAH, PCCA, PCCB, PCDH15, PEX1, PEX7, PKHD1, PMM2, PPT1, RMRP, SACS, SLC12A6, SLC17A5, SLC26A2, SLC37A4, SMPD1, TMEM216, TPP1, ACADVL, ACAT1, AD- AMTS2, ALPL, AMT, ARSB, BBS2, COL4A3, COX15, CPS1, CPT2, CTSA, DHDDS, ERCC5, FMR1, FOXRED1, FUCA1, GALNS, GAMT, GLB1, GNPTAB, GNS, GUSB, HGSNAT, IDS, IL2RG, MANBA, MPL, MTTP, NAGLU, NDUFAF2, NDUFS4, NDUFS7, NDUFV1, NEU1, OTC, PDHA1, PEX10, PEX12, PEX2, PEX26, PEX6, PHGDH, RTEL1, SGSH, SLC22A5, SLC25A20, SLC35A3, SMN1, SUMF1, SURF1, TTPA, VPS13B, XPA and XPC. Inheritest Gene-specific Sequencing, NGS Test Includes Full gene sequencing for any one of the following genes: ABCC8, ACADM, ADA, AGA, AGL, AGXT, AL- DH3A2, ALDOB, ARSA, ASL, ASPA, ASS1, ATM, ATP7B, BBS1, BBS10, BCKDHA, BCKDHB, BCS1L, BLM, CBS, CFTR, CLN3, CLN5, CLN8, CLRN1, CTNS, DHCR7, DLD, DPYD, ETHE1, FAH, FANCC, FKTN, G6PC, GAA, GALC, GALT, GBA, GCDH, GLDC, GRHPR, GSS, HADHA, HBB, HEXA, HEXB, HLCS, HMGCL, HSD17B4, IDUA, IKBKAP, LAMA3, LAMB3, LAMC2, LRPPRC, MAN2B1, MCOLN1, MEFV, MMAA, MMAB, MMACHC, MUT, NBN, NEB, NPC1, NPC2, NPHS1, NPHS2, PAH, PCCA, PCCB, PCDH15, PEX1, PEX7, PKHD1, PMM2, PPT1, RMRP, SACS, SLC12A6, SLC17A5, SLC26A2, SLC37A4, SMPD1, TMEM216, TPP1, ACADVL, ACAT1, ADAMTS2, ALPL, AMT, ARSB, BBS2, COL4A3, COX15, CPS1, CPT2, CTSA, DHDDS, ERCC5, FMR1, FOXRED1, FUCA1, GALNS, GAMT, GLB1, GNPTAB, GNS, GUSB, HGSNAT, IDS, IL2RG, MANBA, MPL, MTTP, NAGLU, NDUFAF2, NDUFS4, NDUFS7, NDUFV1, NEU1, OTC, PDHA1, PEX10, PEX12, PEX2, PEX26, PEX6, PHGDH, RTEL1, SGSH, SLC22A5, SLC25A20, SLC35A3, SMN1, SUMF1, SURF1, TTPA, VPS13B, XPA and XPC. This test is available for partner testing when a carrier is identified through universal carrier screening or for diagnostic testing if indicated. Inheritest Society-guided Screening Panel, NGS Test Includes Screening for 12 genes, including fragile X carrier screening and spinal muscular atrophy (SMA) carrier screening. This test includes: ASPA, BLM, CFTR, FANCC, FMR1, GBA, HBB, HEXA, IKBKAP, MCOLN1, SMN1 and SMPD1. Microsatellite Instability Analysis Specimen One paraffin-embedded tumor and either whole blood or paraffin-embedded normal tissue Neuromyelitis Optica, IgG Autoantibodies Collection If a red-top tube is used, transfer separated serum to a plastic transport tube. Protoporphyrin, Free Erythrocyte, and Zinc Protoporphyrin Protoporphyrin, Free Erythrocyte, and Zinc Protoporphyrin, Workplace Stability Temperature Room temperature Refrigerated Causes for Rejection Clotted specimen; frozen specimen Retinol-binding Protein (RbP) Reference Interval See table. Age Period 14 days 14 days Range (mg/dl) 0 to 12 y to 60 y to 80 y >80 y

5 SCN1A Family-targeted Sequencing Test Includes This test only covers the exon or amplicon that harbors the variant of interest. Other regions of the gene will not be examined. Use This test is intended for testing of additonal family members once a pathogenic variant or variant of uncertain significance has been identified in an affected individual. This option is available when the mutation is known and can be documented by the ordering physician. If the mutation cannot be documented, please order full gene sequencing. Limitations This method does not reliably detect mosaic variants; large deletions; large duplications, inversions, or other rearrangements; deep intronic variants or variants outside of the regions targeted by this analysis. It may be affected by allele-dropout, it may not allow determination of the exact numbers of T/A or microsatellite repeats, and it does not allow any conclusion as to whether two heterozygous variants are present on the same or on different chromosome copies. Results of this test are for investigational purposes only. The performance characteristics of this assay have been determined by LabCorp. The result should not be used as a diagnostic procedure without confirmation of the diagnosis by another medically established diagnostic product or procedure. Methodology DNA sequencing Additional Information SCN1A-related seizure disorders encompass a spectrum of autosomal dominant disorders that ranges from simple febrile seizures (FS) and generalized epilepsy with febrile seizures plus (GEFS+) at the mild end to Dravet syndrome and intractable childhood epilepsy with generalized tonic-clonic seizures (ICE-GTC) at the severe end. Less commonly observed phenotypes include myoclonic-astatic epilepsy (MAE or Doose syndrome), Lennox-Gastaut syndrome (LGS), infantile spasms, and vaccine-related encephalopathy and seizures. Individuals with seizures on the more severe end of the spectrum most often carry a de novo pathogenic variant while individuals on the milder end of the spectrum often have an inherited pathogenic variant. In addition, the clinical presentation of family members carrying the same pathogenic SCN1A variant can vary. Consequently, testing combined with a detailed clinical history is recommended for the parents of any child with a SCN1A pathogenic variant or variant of uncertain significance. SCN1A Sequencing, Full Gene Test Includes This test covers all coding nucleotides of gene SCN1A, plus at least two and typically 20 flanking intronic nucleotides upstream and downstream of each coding exon, covering the conserved donor and acceptor splice sites, as well as typically 20 flanking nucleotides in the 5 and 3 UTR. Use Confirms a diagnosis of a SCN1A-related seizure disorder, including but not limited to severe myoclonic epilepsy of infancy (SMEI, also known as Dravet Syndrome), intractable childhood epilepsy with generalized tonic-clonic seizures (ICE-GTC), generalize epilepsy with febrile seizures plus (GEFS+). Limitations This method does not reliably detect mosaic variants; large deletions; large duplications, inversions, or other rearrangements; deep intronic variants or variants outside of the regions targeted by this analysis. It may be affected by allele-dropout, it may not allow determination of the exact numbers of T/A or microsatellite repeats, and it does not allow any conclusion as to whether two heterozygous variants are present on the same or on different chromosome copies. Results of this test are for investigational purposes only. The performance characteristics of this assay have been determined by LabCorp. The result should not be used as a diagnostic procedure without confirmation of the diagnosis by another medically established diagnostic product or procedure. Methodology DNA sequencing Additional Information SCN1A-related seizure disorders encompass a spectrum of autosomal dominant disorders that ranges from simple febrile seizures (FS) and generalized epilepsy with febrile seizures plus (GEFS+) at the mild end to Dravet syndrome and intractable childhood epilepsy with generalized tonic-clonic seizures (ICE-GTC) at the severe end. Less commonly observed phenotypes include myoclonic-astatic epilepsy (MAE or Doose syndrome), Lennox-Gastaut syndrome (LGS), infantile spasms, and vaccine-related encephalopathy and seizures. Individuals with seizures on the more severe end of the spectrum most often carry a de novo pathogenic variant while individuals on the milder end of the spectrum often have an inherited pathogenic variant. In addition, the clinical presentation of family members carrying the same pathogenic SCN1A variant can vary. Consequently, testing combined with a detailed clinical history is recommended for the parents of any child with a SCN1A pathogenic variant or variant of uncertain significance. Strongyloides, IgG Antibody, Qualitative, EIA Storage Instructions Room temperature Stability Temperature Room temperature Refrigerated Frozen Freeze/thaw cycles Period 16 days 16 days 16 days stable x4 5

6 Testosterone, Total Reference Interval See table. Tanner Stage Additional Information (changes made to the following paragraph) Diminished testosterone production is one of many potential causes of infertility in males. 3,4 Low testosterone concentrations can be caused by testicular failure (primary hypogonadism) or inadequate stimulation by pituitary gonadotropins (secondary hypogonadism). Since men with hypogonadism often have high SHBG levels, the measurement of free or bioavailable testosterone has been advocated when total testosterone levels are normal in men with symptoms of androgen deficiency. 5 Significant physiological changes occur in men as they age, in part due to a gradual decline in testosterone levels. 6,7 It is generally accepted that the principal cause of this age-related decrease in testosterone production is testicular failure, although diminished gonadotropin production may play a role. 5 By 75 years of age, the average male testosterone drops to 65% of average level in young adults. Andropause is a term that has been used to refer to the constellation of symptoms associated with the age-related decline in testosterone production in men. 5,8 The adult male reference range for testosterone was established by Travison and coworkers through an epidemiologic study that included men from different geographic regions of the United States and Europe. 9 Testosterone measurment was harmonized to the Center for Disease Control reference method. 9 The reference population included only men younger than 40 years of age who had a BMI less than 30. Much smaller amounts of testosterone and dihydrotestosterone are produced in women than in men. 2,3 Weaker adrenal androgens and ovarian precursor molecules including androstenedione, DHEA, and DHEA sulfate can have significant androgenic effects in women. The ovary and adrenal glands produce some testosterone, but the majority of the testosterone in women is derived from the peripheral conversion of other steroids. Often, the first sign of testosterone excess in women is the development of male pattern hair growth, which is referred to as hirsutism. 1,3,4,10 It should be noted that some women experience hair growth similar to that caused by increased testosterone due to racial or genetic causes and not due to excessive androgens. Measurement of the testosterone may help to distinguish racial or genetic causes of hirsutism from the abnormal pathology, particularly in women with mixed ethnic backgrounds. Women with more excessive testosterone levels may also experience virilization, with symptoms including increased muscle mass, redistribution of body fat, enlargement of the clitoris, deepening of the voice, and acne and increased perspiration. These women can also suffer from androgenic alopecia, the female equivalent of male pattern baldness. Footnotes (changes made to the following) 9. Travison TG, Vesper HW, Orwoll E, et al. Harmonized reference ranges for circulating testosterone levels in men of four cohort studies in the USA and Eroupe. J Clin Endocrinol Metab (in press). Male Testosterone (ng/dl) Female Testosterone (ng/dl I <3 <3 6 II <3 432 <3 10 III <3 24 IV <3-27 V Adult Male Adult Female >18 y: to 49 y: 8 48 >49 y:

7 Testosterone, Total, Women, Children, and Hypogonadal Males, LC/MS-MS Reference Interval See table. Male Trypsin Storage Instructions Freeze. premature (26 to 28 weeks) day 4 premature (31 to 35 weeks) day 4 newborns Additional Information (changes made to the following paragraph) The adult male reference range for testosterone was established by Travison and coworkers through an epidemiologic study that included men from different geographic regions of the United States and Europe. 5 Testosterone measurment was harmonized to the Center for Disease Control reference method. 5 The reference population included only men younger than 40 years of age who had a BMI less than 30. Footnotes (changes made to the following) 5. Travison TG, Vesper HW, Orwoll E, et al. Harmonized reference ranges for circulating testosterone levels in men of four cohort studies in the USA and Eroupe. J Clin Endocrinol Metab (in press). Tumor Necrosis Factor-α Reference Interval pg/ml Causes for Rejection Nonfrozen specimen; nonserum specimen; gross lipemia; gross hemolysis (ng/dl) to 7 months: Levels decrease rapidly the first week to ng/dl, then increase to ng/dl (mean = 190.0) between 20 to 60 days. Levels then decline to prepubertal range levels of < by seven months. Female premature (26 to 28 weeks) day 4 premature (31 to 35 weeks) day 4 newborns (ng/dl) to 7 months: Levels decrease during the first month to <10.0 and remain there until puberty. Prepubertal Children male (1 to 10 years) female (1 to 9 years) Tanner Stage (ng/dl) < < Stage Age (y) Male (ng/dl) I <9.8 < II 9.8 to III 10.7 to IV 11.8 to V 12.8 to Stage Age (y) Female (ng/dl) I <9.2 < II 9.2 to III 10.0 to IV 10.7 to V 11.8 to Adult Male >18 years premenopausal postmenopausal Adult Female

8 CPT Code Updates Test Name Test No. CPT(s) Gabapentin, Urine Deleted Procedures Deleted Tests Test No. LabCorp Offers Test No. HistoPlus : Lung Cancer Contact your LabCorp representative for available testing options. Human T-Cell Lymphotropic Virus 1, 2 (HTLV-1/HTLV-2), DNA PCR Contact your LabCorp representative for available testing options. RAS Pathway Mutation Profile (KRAS, NRAS), Extended RAS/RAF Pathway Mutation Profile (KRAS and NRAS reflex to BRAF) Substance Abuse Monitoring and Rehabilitation Profile, Urine (Screen and Confirmation) (LabCorp MedWatch ) Substance Abuse Monitoring and Rehabilitation Profile, Urine (Screen With Confirmation) Virus, Direct Detection DFA, Cytomegalovirus (CMV) Virus, Direct Detection DFA, Herpes Simplex Virus (HSV) Cytomegalovirus (CMV), Qualitative, PCR Viral Culture, Rapid, Cytomegalovirus (CMV) Herpes Simplex Virus (HSV) Types 1/2, DNA PCR Herpes Simplex Virus (HSV) Culture and Typing The CPT codes listed are in accordance with the current edition of Current Procedural Terminology, a publication of the American Medical Association. CPT codes are provided for the convenience of our clients; however, correct coding often varies from one carrier to another. Consequently, the codes presented here are intended as general guidelines and should not be used without confirming with the applicable payer that their use is appropriate in each case. LOINC Map. The Logical Observation Identifiers Names and Codes (LOINC ) corresponding to the individual LabCorp published assays is updated on a regular basis at Laboratory Corporation of America Holdings All Rights Reserved. L