rochester 2020 interpretive handbook · 2020-01-03 · and are not necessarily correct....

Rochester2020 Interpretive Handbook

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Current as of January 29, 2020 12:07 pm CST

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Definition of Specimen "Minimum Volume"

Defines the amount of specimen required to perform an assay once, including instrument and container deadspace. Submitting the minimum specimen volume makes it impossible to repeat the test or perform confirmatoryor perform reflex testing. In some situations, a minimum specimen volume may result in a QNS (quantity notsufficient) result, requiring a second specimen to be collected.

Current as of January 29, 2020 12:07 pm CST 800-533-1710 or 507-266-5700 or mayocliniclabs.com Page 1

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Effective Date: 11/12/2018

Policies Mayo Clinic Laboratories

POLICY STATEMENTS Animal Specimens We do not accept animal specimens for laboratory testing. Billing Client—Each month you will receive an itemized invoice/ statement which will indicate the date of service, patient name, CPT code, test name, and test charge. Payment terms are net 30 days. When making payment, please include our invoice number on your check to ensure proper credit to your account. Patient—Mayo Clinic Laboratories does not routinely bill patient’s insurance; however, if you have made advanced arrangements to have Mayo Clinic Laboratories bill your patient’s insurance, please include the following required billing information: responsible party, patient’s name, current address, zip code, phone number, Social Security number, and diagnosis code. Providing this information will avoid additional correspondence to your office at some later date. Please advise your patients that they will receive a bill for laboratory services from Mayo Clinic Laboratories for any personal responsibility after insurance payment. VISA® and MasterCard® are acceptable forms of payment. Billing—CPT Coding It is your responsibility to determine correct CPT codes to use for billing. While this catalog lists CPT codes in an effort to provide some guidance, CPT codes listed only reflect our interpretation of CPT coding requirements and are not necessarily correct. Particularly, in the case of a test involving several component tests, this catalog attempts to provide a comprehensive list of CPT codes for all of the possible components of the test. Only a subset of component tests may be performed on your specimen. You should verify accuracy of codes listed. Where multiple codes are listed, you should select codes for tests actually performed on your specimen. MAYO CLINIC LABORATORIES ASSUMES NO RESPONSIBILITY FOR BILLING ERRORS DUE TO RELIANCE ON CPT CODES LISTED IN THIS CATALOG. For further reference, please consult the CPT Coding Manual published by the American Medical Association. If you have any questions regarding use of a code, please contact your local Medicare carrier. Business Continuity and Contingency Planning In the event of a local, regional, or national disaster, Mayo Clinic and Mayo Clinic Laboratories’ performing sites have comprehensive contingency plans in place in each location to ensure that the impact on laboratory practice is minimized. With test standardization between our performing sites and medical practice locations throughout the country, we have worked to ensure that patient care will not be compromised. Cancellation of Tests Cancellations received prior to test setup will be honored at no charge. Requests received following test setup cannot be honored. A report will be issued automatically and charged appropriately. Chain-of-Custody Chain-of-custody, a record of disposition of a specimen to document who collected it, who handled it, and who performed the analysis, is necessary when results are to be used in a court of law. Mayo Clinic Laboratories has developed packaging and shipping materials that satisfy legal requirements for chain-of-custody. This service is only offered for drug testing.


Effective Date: 11/12/2018 Compliance Policies Mayo Clinic Laboratories is committed to compliance with applicable laws and regulations such as the Clinical Laboratory Improvement Amendments (CLIA). Regulatory agencies that oversee our compliance include, but are not limited to, the Centers for Medicare and Medicaid Services (CMS), the Food and Drug Administration (FDA), and the Department of Transportation (DOT). Mayo Clinic Laboratories develops, implements, and maintains policies, processes, and procedures throughout our organization which are designed to meet relevant requirements. We expect clients utilizing our services will ensure their compliance with patient confidentiality, diagnosis coding, anti-kick back statutes, professional courtesy, CPT-4 coding, CLIA proficiency testing, and other similar regulatory requirements. Also see “Accreditation and Licensure,” “HIPAA Compliance,” and “Reportable Disease.” Confidentiality of Results Mayo Clinic Laboratories is committed to maintaining confidentiality of patient information. To ensure Health Insurance Portability and Accountability Act of 1996 (HIPAA) and the College of American Pathologists (CAP) compliance for appropriate release of patient results, Mayo Clinic Laboratories has adopted the following policies: Phone Inquiry Policy—One of the following unique identifiers will be required: • Mayo Clinic Laboratories’ accession ID number for specimen; or • Client account number from Mayo Clinic Laboratories along with patient name; or • Client accession ID number interfaced to Mayo Clinic Laboratories; or • Identification by individual that he or she is, in fact, “referring physician” identified on requisition form

by Mayo Clinic Laboratories’ client Under federal regulations, we are only authorized to release results to ordering physicians or health care providers responsible for the individual patient’s care. Third parties requesting results including requests directly from the patient are directed to the ordering facility. We appreciate your assistance in helping Mayo Clinic Laboratories preserve patient confidentiality. Provision of appropriate identifiers will greatly assist prompt and accurate response to inquiries and reporting.

Critical Values The “Critical Values Policy” of the Department of Laboratory Medicine and Pathology (DLMP), Mayo Clinic, Rochester, Minnesota is described below. These values apply to Mayo Clinic patients as well as external clients of Mayo Clinic Laboratories. Clients should provide “Critical Value” contact information to Mayo Laboratory Inquiry to facilitate call-backs. To facilitate this process, a customized form is available at mayocliniclabs.com. Definition of Critical Value—A critical value is defined as a value that represents a pathophysiological state at such variance with normal (expected values) as to be life-threatening unless something is done promptly and for which some corrective action could be taken. Abnormals are Not Considered Critical Values— Most laboratory tests have established reference ranges, which represent results that are typically seen in a group of healthy individuals. While results outside these reference ranges may be considered abnormal, “abnormal” results and “critical values” are not synonymous. Analytes on the DLMP Critical Values List represent a subgroup of tests that meet the above definition. Action Taken when a Result is Obtained that Exceeds the Limit Defined by the DLMP Critical Values List—In addition to the normal results reporting (eg, fax, interface), Mayo Clinic Laboratories’ staff telephone the ordering physician or the client-provided contact number within 60 minutes following laboratory release of the critical test result(s). In the event that contact is not made within the 60-minute period, we continue to telephone until the designated party is reached and the result is conveyed in compliance and adherence to the CAP. Current as of January 29, 2020 12:07 pm CST 800-533-1710 or 507-266-5700 or mayocliniclabs.com Page 3

Effective Date: 11/12/2018 Semi-Urgent Results— Semi-Urgent Results are defined by Mayo Clinic as those infectious disease-related results that are needed promptly to avoid potentially serious health consequences for the patient (or in the case of contagious diseases, potentially serious health consequences to other persons exposed to the patient) if not acknowledged and/or treated by the physician. While not included on the Critical Values List, this information is deemed important to patient care in compliance and adherence to the CAP. To complement Mayo Clinic Laboratories’ normal reporting mechanisms (eg, fax, interface), Mayo Clinic Laboratories’ staff will telephone results identified as significant microbiology findings to the ordering facility within 2 hours following laboratory release of the result(s). In the event that contact is not made within the 2-hour period, we will continue to telephone until the responsible party is reached and the result is conveyed. In addition, in most instances, you will see the comment SIGNIFICANT RESULT appear on the final report. For information regarding the Mayo Clinic Critical Value List, contact Mayo Laboratory Inquiry at 800-533-1710 or 507-266-5700 or visit mayocliniclabs.com.

Disclosures of Results Under federal regulations, we are only authorized to release results to ordering physicians or other health care providers responsible for the individual patient’s care. Third parties requesting results, including requests directly from the patient, are directed to the ordering facility. Extracted Specimens Mayo Clinic Laboratories will accept extracted nucleic acid for clinical testing, provided it is an acceptable specimen source for the ordered test, if the isolation was performed in a CLIA-certified laboratory or a laboratory meeting equivalent requirements as determined by the CAP and/or the CMS. Fee Changes Fees are subject to change without notification and complete pricing per accession number is available once accession number is final. Specific client fees are available by calling Mayo Laboratory Inquiry at 800-533-1710 or 507-266-5700 or by visiting mayocliniclabs.com. Framework for Quality “Framework for Quality” is the foundation for the development and implementation of the quality program for Mayo Clinic Laboratories. Our framework builds upon the concepts of quality control and quality assurance providing an opportunity to deliver consistent, high-quality and cost-effective service to our clients. In addition, our quality program enhances our ability to meet and exceed the requirements of regulatory/ accreditation agencies and provide quality service to our customers. A core principle at Mayo Clinic Laboratories is the continuous improvement of all processes and services that support the care of patients. Our continuous improvement process focuses on meeting the needs of you, our client, to help you serve your patients. “Framework for Quality” is composed of 12 “Quality System Essentials.” The policies, processes, and procedures associated with the “Quality System Essentials” can be applied to all operations in the path of workflow (eg, pre-analytical, analytical, and post-analytical). Performance is measured through constant monitoring of activities in the path of workflow and comparing performance through benchmarking internal and external quality indicators and proficiency testing. Data generated by quality indicators drives process improvement initiatives to seek resolutions to system-wide problems. Mayo Clinic Laboratories utilizes “Failure Modes and Effects Analysis (FMEA),” “Plan Do Study Act (PDSA),” “LEAN,” “Root Cause Analysis,” and “Six Sigma” quality improvement tools to determine appropriate remedial, corrective, and preventive actions. Current as of January 29, 2020 12:07 pm CST 800-533-1710 or 507-266-5700 or mayocliniclabs.com Page 4

Effective Date: 11/12/2018 Quality Indicators—Mayo Clinic Laboratories produces hundreds of Key Performance Indicators for our business and operational areas, and we review them regularly to ensure that we continue to maintain our high standards. A sampling of these metrics includes:

• Pre-analytic performance indicators o Lost specimens* o On-time delivery o Special handling calls o Specimen acceptability* o Specimen identification* o Incoming defects*

• Analytic performance indicators o Proficiency testing o Quality control o Turnaround (analytic) times o Quantity-not-sufficient (QNS) specimens*

• Post-analytic performance indicators o Revised reports* o Critical value reports*

• Operational performance indicators o Incoming call resolution* o Incoming call abandon rate o Call completion rate o Call in-queue monitoring o Customer complaints o Customer satisfaction surveys

The system provides a planned, systematic program for defining, implementing, monitoring, and evaluating our services. *Measured using Six Sigma defects per million (dpm) method.

HIPAA Compliance Mayo Clinic Laboratories is fully committed to compliance with all privacy, security, and electronic transaction code requirements of the Health Insurance Portability and Accountability Act of 1996 (HIPAA). All services provided by Mayo Clinic Laboratories that involve joint efforts will be done in a manner which enables our clients to be HIPAA and the College of American Pathologists (CAP) compliant. Infectious Material The Centers for Disease Control (CDC) in its regulations of July 21, 1980, has listed organisms and diseases for which special packaging and labeling must be applied. Required special containers and packaging instructions can be obtained from us by using the “Request for Supplies” form or by ordering from the online Supply Catalog at mayocliniclabs.com/customer-service/supplies/index.php. Shipping regulations require that infectious substances affecting humans be shipped in a special manner. See “Infectious Material.” A copy of the regulations can be requested from the International Air Transport Association (IATA); they may be contacted by phone at 514-390-6770 or by fax at 514-874-2660. Informed Consent Certification Submission of an order for any tests contained in this catalog constitutes certification to Mayo Clinic Laboratories by ordering physician that: (1) ordering physician has obtained “Informed Consent” of subject patient as required by any applicable state or federal laws with respect to each test ordered; and (2) ordering physician has obtained from subject patient authorization permitting Mayo Clinic Laboratories to report results of each test ordered directly to ordering physician. Current as of January 29, 2020 12:07 pm CST 800-533-1710 or 507-266-5700 or mayocliniclabs.com Page 5

Effective Date: 11/12/2018 On occasion, we forward a specimen to an outside reference laboratory. The laws of the state where the reference laboratory is located may require written informed consent for certain tests. Mayo Clinic Laboratories will request that ordering physician pursue and provide such consent. Test results may be delayed or denied if consent is not provided. Non-Biologic Specimens Due to the inherent exposure risk of non-biologic specimens, their containers, and the implied relationship to criminal, forensic, and medico-legal cases, Mayo Clinic Laboratories does not accept nor refer non-biologic specimen types. Example specimens include: unknown solids and liquids in the forms of pills, powder, intravenous fluids, or syringe contents. Patient Safety Goals One of The Joint Commission National Patient Safety goals for the Laboratory Services Program is to improve the accuracy of patient identification by using at least 2 patient identifiers when providing care, treatment, or services. Mayo Clinic Laboratories uses multiple patient identifiers to verify the correct patient is matched with the correct specimen and the correct order for the testing services. As a specimen is received at Mayo Clinic Laboratories, the client number, patient name, and patient age date of birth are verified by comparing the labels on the specimen tube or container with the electronic order and any paperwork (batch sheet or form) which may accompany the specimen to be tested. When discrepancies are identified, Mayo Laboratory Inquiry will call the client to verify discrepant information to assure Mayo Clinic Laboratories is performing the correct testing for the correct patient. When insufficient or inconsistent identification is submitted, Mayo Clinic Laboratories will recommend that a new specimen be obtained, if feasible. In addition, Anatomic Pathology consultation services require the Client Pathology Report. The pathology report is used to match the patient name, patient age and/or date of birth, and pathology case number. Since tissue blocks and slides have insufficient space to print the patient name on the block, the pathology report provides Mayo Clinic Laboratories another mechanism to confirm the patient identification with the client order and labels on tissue blocks and slides. Parallel Testing Parallel testing may be appropriate in some cases to re-establish patient baseline results when converting to a new methodology at Mayo Clinic Laboratories. Contact your Regional Manager at 800-533-1710 or 507-266-5700 for further information. Proficiency Testing We are a College of American Pathologists (CAP)-accredited, CLIA-licensed facility that voluntarily participates in many diverse external and internal proficiency testing programs. It is Mayo Clinic Laboratories’ expectation that clients utilizing our services will adhere to CLIA requirements for proficiency testing (42 CFR 493.801), including a prohibition on discussion about samples or results and sharing of proficiency testing materials with Mayo Clinic Laboratories during the active survey period. Mayo Clinic Laboratories’ proficiency testing includes participation in CMS-approved programs. Mayo Clinic Laboratories also performs alternative assessment using independent state, national, and international programs when proficiency testing is not available. Mayo Clinic Laboratories also conducts comparability studies to ensure the accuracy and reliability of patient testing, when necessary. We comply with the regulations set forth in Clinical Laboratory Improvement Amendments (CLIA-88), the Occupational Safety and Health Administration (OSHA), or the Centers for Medicare & Medicaid Services (CMS). It is Mayo Clinic Laboratories’ expectation that clients utilizing our services will adhere to CLIA requirements for proficiency testing including a prohibition on discussion about samples or results and sharing of proficiency Current as of January 29, 2020 12:07 pm CST 800-533-1710 or 507-266-5700 or mayocliniclabs.com Page 6

Effective Date: 11/12/2018 testing materials with Mayo Clinic Laboratories during the active survey period. Referring of specimens is acceptable for comparison purposes when an approved proficiency-testing program is not available for a given analyte. Radioactive Specimens Specimens from patients receiving radioactive tracers or material should be labeled as such. All incoming shipments arriving at Mayo Clinic Laboratories are routed through a detection process in receiving to determine if the samples have any levels of radioactivity. If radioactive levels are detected, the samples are handled via an internal process that assures we do not impact patient care and the safety of our staff. This radioactivity may invalidate the results of radioimmunoassays (RIA). Record Retention Mayo Clinic Laboratories retains all test requisitions and patient test results at a minimum for the retention period required to comply with and adhere to the CAP. A copy of the original report can be reconstructed including reference ranges, interpretive comments, flags, and footnotes with the source system as the Department of Laboratory Medicine’s laboratory information system. Referral of Tests to Another Laboratory Mayo Clinic Laboratories forwards tests to other laboratories as a service to its clients. This service should in no way represent an endorsement of such test or referral laboratory or warrant any specific performance for such test. Mayo Clinic Laboratories will invoice for all testing referred to another laboratory at the price charged to Mayo Clinic Laboratories. In addition, Mayo Clinic Laboratories will charge an administrative fee per test for such referral services. Reflex Testing Mayo Clinic Laboratories identifies tests that reflex when medically appropriate. In many cases, Mayo Clinic Laboratories offers components of reflex tests individually as well as together. Clients should familiarize themselves with the test offerings and make a decision whether to order a reflex test or an individual component. Clients, who order a reflex test, can request to receive an “Additional Testing Notification Report” which indicates the additional testing that has been performed. This report will be faxed to the client. Clients who wish to receive the “Additional Testing Notification Report” should contact their Regional Manager or Regional Service Representative. Reportable Disease Mayo Clinic Laboratories, in compliance with and adherence to the College of American Pathologists (CAP) Laboratory General Checklist (CAP GEN. 20373) strives to comply with laboratory reporting requirements for each state health department regarding reportable disease conditions. We report by mail, fax, and/or electronically, depending upon the specific state health department regulations. Clients shall be responsible for compliance with any state specific statutes concerning reportable conditions, including, but not limited to, birth defects registries or chromosomal abnormality registries. This may also include providing patient address/demographic information. Mayo Clinic Laboratories’ reporting does not replace the client or physician responsibility to report as per specific state statues. Request for Physician Name and Number Mayo Clinic Laboratories endeavors to provide high quality, timely results so patients are able to receive appropriate care as quickly as possible. While providing esoteric reference testing, there are times when we need to contact the ordering physician directly. The following are 2 examples:

When necessary to the performance of a test, the ordering physician’s name and phone number are requested as part of “Specimen Required.” This information is needed to allow our physicians to make timely consultations or seek clarification of requested services. If this information is not provided at the time of specimen receipt, we will call you to obtain the information. By providing this information up front, delays in patient care are avoided.



In some situations, additional information from ordering physician is necessary to clarify or interpret a test result. At that time, Mayo Clinic Laboratories will request physician’s name and phone number so that one of our staff can consult with the physician.

We appreciate your rapid assistance in supplying us with the ordering physician’s name and phone number when we are required to call. Working together, we can provide your patients with the highest quality testing services in the shortest possible time. Special Handling Mayo Clinic Laboratories serves as a reference laboratory for clients around the country and world. Our test information, including days and time assays are performed as well as analytic turnaround time, is included under each test listing in the Test Catalog on mayocliniclabs.com. Unique circumstances may arise with a patient resulting in a physician request that the specimen or results receive special handling. There are several options available. These options can only be initiated by contacting Mayo Laboratory Inquiry at 800-533-1710 or 507-266-5700 and providing patient demographic information. There is a nominal charge associated with any special handling.

• Hold: If you would like to send us a specimen and hold that specimen for testing pending initial test results performed at your facility, please call Mayo Laboratory Inquiry. We will initiate a hold and stabilize the specimen until we hear from you.

• Expedite: If you would like us to expedite the specimen to the performing laboratory, you can call Mayo Laboratory Inquiry and request that your specimen be expedited. Once the shipment is received in our receiving area, we will deliver the specimen to the performing laboratory for the next scheduled analytic run. We will not set up a special run to accommodate an expedite request.

• STAT: In rare circumstances, STAT testing from the reference laboratory may be required for patients who need immediate treatment. These cases typically necessitate a special analytic run to turn results around as quickly as possible. To arrange STAT testing, please have your pathologist, physician, or laboratory director call Mayo Laboratory Inquiry. He/she will be connected with one of our medical directors to consult about the patient’s case. Once mutually agreed upon that there is a need for a STAT, arrangements will be made to assign resources to run the testing on a STAT basis when the specimen is received.

Specimen Identification Policy In compliance with and adherence to the CAP and the Joint Commission’s 2008 Patient Safety Goals (1A), Mayo Clinic Laboratories’ policy states that all specimens received for testing must be correctly and adequately labeled to assure positive identification. Specimens must have 2 person-specific identifiers on the patient label. Person-specific identifiers may include: accession number, patient’s first and last name, unique identifying number (eg, medical record number), or date of birth. Specimens are considered mislabeled when there is a mismatch between the person-specific identifiers on the specimen and information accompanying the specimen (eg, computer system, requisition form, additional paperwork). When insufficient or inconsistent identification is submitted, Mayo Clinic Laboratories will recommend that a new specimen be obtained, if feasible. Specimen Rejection All tests are unique in their testing requirements. To avoid specimen rejection or delayed turnaround times, please check the “Specimen Required” field within each test. You will be notified of rejected or problem specimens upon receipt. Please review the following conditions prior to submitting a specimen to Mayo Clinic Laboratories:

• Full 24 hours for timed urine collection Current as of January 29, 2020 12:07 pm CST 800-533-1710 or 507-266-5700 or mayocliniclabs.com Page 8


• pH of urine • Lack of hemolysis/lipemia • Specimen type (plasma, serum, whole blood, etc.) • Specimen volume • Patient information requested • Proper identification of patient/specimen • Specimen container (metal-free, separation gel, appropriate preservative, etc.) • Transport medium • Temperature (ambient, frozen, refrigerated)

Specimen Volume The “Specimen Required” section of each test includes 2 volumes - preferred volume and minimum volume. Preferred volume has been established to optimize testing and allows the laboratory to quickly process specimen containers, present containers to instruments, perform test, and repeat test, if necessary. Many of our testing processes are fully automated; and as a result, this volume allows hands-free testing and our quickest turnaround time (TAT). Since patient values are frequently abnormal, repeat testing, dilutions, or other specimen manipulations often are required to obtain a reliable, reportable result. Our preferred specimen requirements allow expeditious testing and reporting. When venipuncture is technically difficult or the patient is at risk of complications from blood loss (eg, pediatric or intensive care patients), smaller volumes may be necessary. Specimen minimum volume is the amount of sample necessary to provide a clinical relevant result as determined by the Testing Laboratory. When patient conditions do not mandate reduced collection volumes, we ask that our clients submit preferred volume to facilitate rapid, cost-effective, reliable test results. Submitting less than preferred volume may negatively impact quality of care by slowing TAT, increasing the hands-on personnel time (and therefore cost) required to perform test. Mayo Clinic Laboratories makes every possible effort to successfully test your patient’s specimen. If you have concerns about submitting a specimen for testing, please call Mayo Laboratory Inquiry at 800-533-1710 or 507-266-5700. Our staff will discuss the test and specimen you have available. While in some cases specimens are inadequate for desired test, in other cases, testing can be performed using alternative techniques. Supplies Shipping boxes, specimen vials, special specimen collection containers, and request forms are supplied without charge. Supplies can be requested using one of the following methods: use the online ordering functionality available at mayocliniclabs.com/supplies or call Mayo Laboratory Inquiry at 800-533-1710 or 507-266-5700. Test Classifications Analytical tests offered by Mayo Clinic Laboratories are classified according to the FDA labeling of the test kit or reagents and their usage. Where appropriate, analytical test listings contain a statement regarding these classifications, test development, and performance characteristics. Test Development Process Mayo Clinic Laboratories serves patients and health care providers from Mayo Clinic, Mayo Health System, and our reference laboratory clients worldwide. We are dedicated to providing clinically useful, cost-effective testing strategies for patient care. Development, validation, and implementation of new and improved laboratory methods are major components of that commitment. Each assay utilized at Mayo Clinic, whether developed on site or by others, undergoes an extensive validation and performance documentation period before the test becomes available for clinical use. Validations follow a standard protocol that includes:

• Accuracy Current as of January 29, 2020 12:07 pm CST 800-533-1710 or 507-266-5700 or mayocliniclabs.com Page 9


• Precision • Sensitivity • Specificity and interferences • Reportable range • Specimen stability • Specimen type comparisons, if applicable • Urine preservative studies: stability at ambient, refrigerated, and frozen temperatures and with 7

preservatives; at 1, 3, and 7 days • Comparative evaluation with current and potential methods, if applicable • Reference intervals: reference intervals provided by Mayo Clinic Laboratories are derived from studies

performed in our laboratories or adopted from the manufacturer package insert after internal verification. When reference intervals are obtained from other sources, the source is indicated in the “Reference Values” field.

• Workload recording • Limitations of the assay • Clinical utility and interpretation: written by Mayo Clinic medical experts, electronically available

(MayoAccess™) Test Result Call-Backs Results will be phoned to a client when requested from the client (either on Mayo Clinic Laboratories’ request form or from a phone call to Mayo Clinic Laboratories from the client). Time-Sensitive Specimens Please contact Mayo Laboratory Inquiry at 800-533-1710 or 507-266-5700 prior to sending a specimen for testing of a time-sensitive nature. Relay the following information: facility name, account number, patient name and/or Mayo Clinic Laboratories’ accession number, shipping information (ie, courier service, FedEx®, etc.), date to be sent, and test to be performed. Place specimen in a separate Mayo Clinic Laboratories’ temperature appropriate bag. Please write “Expedite” in large print on outside of bag. Turnaround Time (TAT) Mayo Clinic Laboratories’ extensive test menu reflects the needs of our own health care practice. We are committed to providing the most expedient TAT possible to improve diagnosis and treatment. We consider laboratory services as part of the patient care continuum wherein the needs of the patient are paramount. In that context, we strive to fulfill our service obligations. Our history of service and our quality metrics will document our ability to deliver on all areas of service including TAT. Mayo Clinic Laboratories defines TAT as the analytical test time (the time from which a specimen is received at the testing location to time of result) required. TAT is monitored continuously by each performing laboratory site within the Mayo Clinic Department of Laboratory Medicine and Pathology. For the most up-to-date information on TAT for individual tests, please visit us at mayocliniclabs.com or contact Mayo Laboratory Inquiry at 800-533-1710 or 507-266-5700. Unlisted Tests Mayo Clinic Laboratories does not list all available test offerings in the paper catalog. New procedures are developed throughout the year; therefore, some tests are not listed in this catalog. Although we do not usually accept referred tests of a more routine type, special arrangements may be made to provide your laboratory with temporary support during times of special need such as sustained instrumentation failure. For information about unlisted tests, please call Mayo Laboratory Inquiry at 800-533-1710 or 507-266-5700.


DHVD8822

1,25-Dihydroxyvitamin D, SerumClinical Information: Vitamin D is a generic designation for a group of fat-soluble, structurallysimilar sterols, which act as hormones. In the presence of renal disease or hypercalcemia, testing of1,25-dihydroxy vitamin D (DHVD) might be needed to adequately assess vitamin D status. The25-hydroxyvitamin D (25HDN) test (25HDN / 25-Hydroxyvitamin D2 and D3, Serum) in serum isotherwise the preferred initial test for assessing vitamin D status and most accurately reflects the body'svitamin D stores. Vitamin D compounds in the body are exogenously derived by dietary means; fromplants as 25-hydroxyvitamin D2 (ergocalciferol or calciferol) or from animal products as25-hydroxyvitamin D3 (cholecalciferol or calcidiol). Vitamin D may also be endogenously derived byconversion of 7-dihydrocholesterol to 25-hydroxyvitamin D3 in the skin upon ultraviolet exposure.25HDN is subsequently formed by hydroxylation (CYP2R1) in the liver. 25HDN is a prohormone thatrepresents the main reservoir and transport form of vitamin D, being stored in adipose tissue and tightlybound by a transport protein while in circulation. Biological activity is expressed in the form of DHVD,the active metabolite of 25HDN. 1-Alpha-hydroxylation (CYP27B1) occurs on demand, primarily in thekidneys, under the control of parathyroid hormone (PTH) before expressing biological activity. Likeother steroid hormones, DHVD binds to a nuclear receptor, influencing gene transcription patterns intarget organs. 25HDN may also be converted into the inactive metabolite 24,25-dihydroxyvitamin D(24,25D) by (CYP24A1) hydroxylation. This process, regulated by parathyroid hormone (PTH), mightincrease DHVD synthesis at the expense of the alternative hydroxylation (CYP24A1) product 24,25D.Inactivation of 25HDN and DHVD by CYP24A1 is a crucial process that prevents over production ofDHVD and resultant vitamin D toxicity. DHVD stimulates calcium absorption in the intestine and itsproduction is tightly regulated through concentrations of serum calcium, phosphorus, and PTH. DHVDpromotes intestinal calcium absorption and, in concert with PTH, skeletal calcium deposition, or lesscommonly, calcium mobilization. Renal calcium and phosphate reabsorption are also promoted, whileprepro-PTH mRNA expression in the parathyroid glands is downregulated. The net result is a positivecalcium balance, increasing serum calcium and phosphate levels, and falling PTH concentrations. Inaddition to its effects on calcium and bone metabolism, DHVD regulates the expression of a multitudeof genes in many other tissues including immune cells, muscle, vasculature, and reproductive organs.DHVD levels are decreased in hypoparathyroidism and in chronic renal failure. DHVD levels may behigh in primary hyperparathyroidism and in physiologic hyperparathyroidism secondary to low calciumor vitamin D intake. Some patients with granulomatous diseases (eg, sarcoidosis) and malignanciescontaining nonregulated 1-alpha hydroxylase in the lesion might have hypercalcemia that appearsvitamin D mediated with normal or high serum phosphate (hyperphosphatemia) and hypercalcemia(both of which might be severe) in addition to low PTH and absent parathyroid hormone-related peptide(PTHRP). Assessment of 24,25D might also be required in patients with hypercalcemia that does notappear to be driven by PTH or PTHRP, and may be helpful in assessment of patients with loss offunction inactivating CYP24A1 mutations. Differential diagnostic considerations include vitamin Dintoxication and CYP24A1 deficiency.

Useful For: As a second-order test in the assessment of vitamin D status, especially in patients withrenal disease Investigation of some patients with clinical evidence of vitamin D deficiency (eg, vitaminD-dependent rickets due to hereditary deficiency of renal 1-alpha hydroxylase or end-organ resistanceto 1,25-dihydroxyvitamin D) Differential diagnosis of hypercalcemia

Interpretation: 1,25-Dihydroxyvitamin D (DVHD) concentrations are low in chronic renal failureand hypoparathyroidism. DVHD concentrations are high in sarcoidosis and other granulomatousdiseases, some malignancies, primary hyperparathyroidism, and physiologic hyperparathyroidism.DVHD concentrations are not a reliable indicator of vitamin D toxicity; normal (or even low) resultsmay be seen in such cases.

Reference Values: Males: or =16 years: 18-64 pg/mL Females:

> or =16 years: 18-78 pg/mL For SI unit Reference Values, see https://www.mayocliniclabs.com/order-tests/si-unit-conversion.html

Clinical References: 1. Endres DB, Rude RK: Vitamin D and its metabolites. In Tietz Textbook ofClinical Chemisty. Third edition. Edited by CA Burtis, ER Ashwood. Philadelphia, WB SaundersCompany, 1999, pp 1417-1423 2. Bringhurst FR, Demay MB, Kronenberg HM: Vitamin D (calciferols):metabolism of vitamin D. In Williams Textbook of Endocrinology. Ninth edition. Edited by JD Wilson,DW Foster, HM Kronenberg, PR Larsen. Philadelphia, WB Saunders Company, 1998, pp 1166-1169

SFUNG604094

1,3-Beta-D-Glucan (Fungitell), SerumClinical Information: Invasive fungal infections (IFI) due to opportunistic fungal pathogens are asignificant cause of morbidity and mortality, particularly among patients who are significantlyimmunosuppressed including hematopoietic stem cell transplant recipients, solid organ transplantrecipients, and those with hematologic or immune deficiencies. Patient recovery and survival following anIFI is directly related to the timely clinical recognition and prompt administration of antifungal therapy.Laboratory diagnosis of IFI is largely based on direct microscopic examination of patient specimens,histopathologic examination of tissue biopsies, isolation of fungi via culture, and, more recently, throughmolecular methods. However, these techniques commonly require invasive sample collection methods(eg, biopsy, bronchoalveolar lavage), which may be contraindicated in certain patients. Additionally, bothmicroscopy and culture are frequently insensitive, with prior studies showing the sensitivity of culture forinvasive Aspergillus infections ranges from 40% to 85%, and some fungi require prolonged incubationtimes, limiting the utility of culture in the acute patient setting. Due to these limitations, use of fungalbiomarkers, including detection of (1,3)-beta-D-glucan (BDG), have emerged as useful adjunct testsavailable for detection of IFI. BDG is found in the cell walls of most fungi (eg, Candida, Aspergillus,Fusarium, Pneumocystis jirovecii) with the notable exception of Cryptococcus species, Blastomycesspecies, and the Mucorales (eg, Lichthemia, Mucor, Rhizopus), which either lack BDG entirely orproduce it in very low amounts. Elevated serum BDG levels have been associated with the presence of afungal infection, often prior to the development of clinical symptoms and before isolation or identificationof the fungal organism via routine methods. The sensitivity and specificity of BDG detection in patientswith proven or probable IFI ranges from 64% to 93% and 87% to 100%, respectively, among differentstudies. Importantly, the BDG assay should not be used alone to diagnose an IFI, but rather in conjunctionwith careful evaluation of patient risk factors for infection, other laboratory testing, and radiologicfindings.

Useful For: Aiding in the diagnosis of invasive fungal infections caused by various fungi, includingAspergillus species, Fusarium species, Candida species, and Pneumocystis jiroveccii, among others

Interpretation: The Fungitell assay should be used in conjunction with other diagnostic procedures,such as routine bacterial/fungal cultures, histologic examination of biopsy material and radiologic studies.Positive: (1,3)-Beta-D-glucan detected. A single positive result should be interpreted with caution andcorrelated alongside consideration of patient risk for invasive fungal disease, results of routine laboratorytests (eg, bacterial and fungal culture, histopathologic evaluation) and radiologic findings. Repeat testingon a new sample (collected in 3-4 days) is recommended as serially positive samples are associated with ahigher diagnostic odds ratio for invasive fungal infection compared to a single positive result.False-positive results may occur in patients who have recently (in the past 3-4 days) undergonehemodialysis, treatment with certain fractionated blood products (eg, serum albumin, immunoglobulins),or those who have had significant exposure to glucan-containing gauze during surgery. This assay doesnot detect certain fungi, including Cryptococcus species, which produce very low levels of(1,3)-Beta-D-glucan (BDG) and the Mucorales (eg, Lichthemia, Mucor, and Rhizopus), which are notknown to produce BDG. Additionally, the yeast phase of Blastomyces dermatitidis produces little BDGand may not be detected by this assay. Indeterminate: Repeat testing on a new sample is recommended inpatients at risk for an invasive fungal infection. This assay does not detect certain fungi, includingCryptococcus species, which produce very low levels of (1,3)-Beta-D-glucan (BDG) and the Mucorales(eg, Lichthemia, Mucor, and Rhizopus), which are not known to produce BDG. Additionally, the yeastphase of Blastomyces dermatitidis produces little BDG and may not be detected by this assay. Negative:


No (1,3)-Beta-D-glucan detected. This assay does not detect certain fungi, including Cryptococcusspecies, which produce very low levels of (1,3)-Beta-D-Glucan (BDG) and the Mucorales (eg,Lichthemia, Mucor, and Rhizopus), which are not known to produce BDG. Additionally, the yeast phaseof Blastomyces dermatitidis produces little BDG and may not be detected by this assay.

Reference Values: FUNGITELL QUANTITATIVE VALUE: 90% of cases), with the third most common formof CAH (3-beta-steroid dehydrogenase deficiency,

(associated with cortisol deficiency) -The rarer CYP11B2 deficiency (no cortisol deficiency) -The yetless common glucocorticoid-responsive hyperaldosteronism (where expression of the gene CYP11B2 isdriven by the CYP11B1 promoter, thus making it responsive to adrenocorticotrophic hormone: ACTHrather than renin) For other forms of CAH, the following tests might be relevant: -11-Hydroxylasedeficiency: - DOC / 11-Deoxycortisol, Serum - CORTC / Corticosterone, Serum - HYD18 /Hydroxycorticosterone, 18 - PRA / Renin Activity, Plasma - ALDS / Aldosterone, Serum-3-Beta-steroid-dehydrogenase deficiency: - 17PRN / Pregnenolone and 17-Hydroxypregnenolone-17-Hydroxylase deficiency or 17-lyase deficiency (CYP17A1 has both activities): - PREGN /Pregnenolone, Serum - 17OHP / 17-Hydroxypregnenolone, Serum - PGSN / Progesterone, Serum -OHPG / 17-Hydroxyprogesterone, Serum - DHEA / Dehydroepiandrosterone (DHEA), Serum - ANST /Androstenedione, Serum Cortisol should be measured in all cases of suspected CAH. In the diagnosis ofsuspected 11-hydroxylae deficiency and glucocorticoid-responsive hyperaldosteronism, this test shouldbe used in conjunction with measurements of 11-deoxycortisol, corticosterone,18-hydroxycorticosterone, cortisol, renin, and aldosterone.

Useful For: Diagnosis of suspected 11-hydroxylase deficiency, including the differential diagnosis of11 beta-hydroxylase 1 (CYP11B1) versus 11 beta-hydroxylase 2 (CYP11B2) deficiency, and in thediagnosis of glucocorticoid-responsive hyperaldosteronism Evaluating congenital adrenal hyperplasianewborn screen-positive children, when elevations of 17-hydroxyprogesterone are only moderate,suggesting possible 11-hydroxylase deficiency

Interpretation: In 11 beta-hydroxylase 1 (CYP11B1) deficiency, serum concentrations of cortisol willbe low (usually

CYP11B2 deficiency. Sex steroid levels in glucocorticoid-responsive hyperaldosteronism are usuallynormal. Most untreated patients with 21-hydroxylase deficiency have serum 17-hydroxyprogesteroneconcentrations well in excess of 1,000 ng/dL. For the few patients with levels in the range of higher than630 ng/dL (upper limit of reference range for newborns) to 2,000 or 3,000 ng/dL, it might be prudent toconsider 11-hydroxylase deficiency as an alternative diagnosis. This is particularly true if serumandrostenedione concentrations are also only mildly to modestly elevated, and if the phenotype is not saltwasting but either simple virilizing (female) or normal (female or male). 11-Hydroxylase deficiency, inparticular if it affects CYP11B1, can be associated with modest elevations in serum17-hydroxyprogesterone concentrations. In these cases, testing for CYP11B1 deficiency and CYB11B2deficiency should be considered and interpreted as described above. Alternatively, measurement of21-deoxycortisol might be useful. This minor pathway metabolite accumulates in CYP21A2 deficiency,as it requires 21-hydroxylaion to be converted to cortisol, but is usually not elevated in CYP11B1deficiency, since its synthesis requires via 11-hydroxylation of 17-hydroxyprogesterone.

Reference Values: < or =18 years: 18 years: cortisol Compound S is typically increased whenadrenocorticotropic hormone (ACTH) levels are increased (eg, Cushing disease, ACTH-producingtumors) or in 11 beta-hydroxylase deficiency, a rare subform of congenital adrenal hyperplasia (CAH).In CAH due to 11 beta-hydroxylase deficiency, cortisol levels are low, resulting in increased pituitaryACTH production and increased serum and urine 11-deoxycortisol levels. Pharmacological blockade of11 beta-hydroxylase with metyrapone can be used to assess the function of thehypothalamic-pituitary-adrenal axis (HPA). In this procedure metyrapone is administered to patients,and serum 11-deoxycortisol levels or urinary 17-hydroxy steroid levels are measured either at baseline(midnight) and 8 hours later (overnight test), or at baseline and once per day during a 2-day metyraponetest (4-times a day metyrapone administration over 2 days). Two-day metyrapone testing has beenlargely abandoned because of the logistical problems of multiple timed urine and blood collections andthe fact that overnight testing provides very similar results. In either case, the normal response tometyrapone administration is a fall in serum cortisol levels, triggering a rise in pituitary ACTHsecretion, which, in turn, leads to a rise in 11-deoxycortisol levels due to the ongoing11-deoxycortisol-to-cortisol conversion block. In the diagnostic workup of suspected adrenalinsufficiency, the results of overnight metyrapone testing correlate closely with the gold standard ofHPA-axis assessment, insulin hypoglycemia testing. Combining 11-deoxycortisol measurements withACTH measurements during metyrapone testing further enhances the performance of the test.Impairment of any component of the HPA-axis results in a subnormal rise in 11-deoxycortisol levels.By contrast, standard-dose or low-dose ACTH(1-24) (cosyntropin)-stimulation testing, which forms thebackbone for diagnosis of primary adrenal failure (Addison disease), only assess the ability of the


adrenal cells to respond to ACTH stimulation. While this allows unequivocal diagnosis of primaryadrenal failure, in the setting of secondary or tertiary adrenal insufficiency, metyrapone testing is moresensitive and specific than either standard-dose or low-dose ACTH(1-24)-stimulation testing.Metyrapone testing is also sometimes employed in the differential diagnosis of Cushing syndrome. InCushing disease (pituitary-dependent ACTH overproduction), the ACTH-hypersecreting pituitary tissueremains responsive to the usual feedback stimuli, just at a higher "set-point" than in the normal state,resulting in increased ACTH secretion and 11-deoxycortisol production after metyraponeadministration. By contrast, in Cushing syndrome due to primary adrenal corticosteroid oversecretion orectopic ACTH secretion, pituitary ACTH production is appropriately shut down and there is usually nofurther rise in ACTH and, hence 11-deoxycortisol, after metyrapone administration. The metyraponetest has similar sensitivity and specificity to the high-dose dexamethasone suppression test in thedifferential diagnosis of Cushing disease, but is less widely used because of the lack of availability of aneasy, automated 11-deoxycortisol assay. In recent years, both tests have been supplanted to some degreeby corticotropin-releasing hormone (CRH)-stimulation testing with petrosal sinus serum ACTHsampling. See Steroid Pathways in Special Instructions.

Useful For: Diagnostic workup of patients with congenital adrenal hyperplasia Part of metyraponetesting in the workup of suspected secondary or tertiary adrenal insufficiency Part of metyrapone testingin the differential diagnostic workup of Cushing syndrome

Interpretation: In a patient suspected of having congenital adrenal hyperplasia (CAH), elevated serum11-deoxycortisol levels indicate possible 11 beta-hydroxylase deficiency. However, not all patients willshow baseline elevations in serum 11-deoxycortisol levels. In a significant proportion of cases, increasesin 11-deoxycortisol levels are only apparent after adrenocorticotropic hormone (ACTH)(1-24)stimulation.(1) Serum 11-deoxycortisol levels below 1,700 ng/dL 8 hours after metyrapone administrationis indicative of probable adrenal insufficiency. The test cannot reliably distinguish between primary andsecondary or tertiary causes of adrenal failure, as neither patients with pituitary failure, nor those withprimary adrenocortical failure, tend to show an increase of 11-deoxycortisol levels after metyrapone isadministered. See Steroid Pathways in Special Instructions.

Reference Values: < or =18 years: 18 years: 10-79 ng/dL For SI unit Reference Values, see https://www.mayocliniclabs.com/order-tests/si-unit-conversion.html

Clinical References: 1. Tonetto-Fernandes V, Lemos-Marini SH, Kuperman H, et al: Serum21-deoxycortisol, 17-hydroxyprogesterone, and 11-deoxycortisol in classic congenital adrenalhyperplasia: clinical and hormonal correlations and identification of patients with 11 beta-hydroxylasedeficiency among a large group with alleged 21-hydroxylase deficiency. J Clin Endocrinol Metab 2006Jun;91(6):2179-2184 2. Lashanske G, Sainger P, Fishman K, et al: Normative data for adrenalsteroidogenesis in a healthy pediatric population: age- and sex-related changes after adrenocorticotropinstimulation. J Clin Endocrinol Metab 1991 Sep;73(3):674-686 3. Holst JP, Soldin SJ, Tractenberg RE, etal: Use of steroid profiles in determining the cause of adrenal insufficiency. Steroids 2007 Jan;72(1):71-844. Berneis K, Staub JJ, Gessler A, et al: Combined stimulation of adrenocorticotropin and compound-S bysingle dose metyrapone test as an outpatient procedure to assess hypothalamic-pituitary-adrenal function.J Clin Endocrinol Metab 2002 Dec;87(12):5470-5475

FDSOX91690

11-Desoxycortisol (Specific Compound S)Reference Values: Age Range Premature (26-28w) Day 4 110-1376 Premature (31-35w) Day 4 48-579 Newborn Day 3 13-147 31d-11m

Pubertal Children and Adults 8:00 AM 12-158

THCMX62744

11-nor-Delta-9-Tetrahydrocannabinol-9-Carboxylic Acid(Carboxy-THC) Confirmation, Chain of Custody, MeconiumClinical Information: Marijuana and other psychoactive products obtained from the plant Cannabissativa are the most widely used illicit drugs in the world.(1) Marijuana has unique behavioral effectsthat include feelings of euphoria and relaxation, altered time perception, impaired learning and memory,lack of concentration, and mood changes (eg, panic reactions and paranoia). Cannabis sativa producesnumerous compounds collectively known as cannabinoids including delta-9-tetrahydrocannabinol(THC), which is the most prevalent and produces most of the characteristic pharmacological effects ofsmoked marijuana.(2) THC undergoes rapid hydroxylation by the cytochrome (CYP) enzyme system toform the active metabolite 11-hydroxy-THC. Subsequent oxidation of 11-hydroxy-THC produces theinactive metabolite 11-nor-delta-9-tetrahydrocannabinol-9-carboxylic acid (THC-COOH;carboxy-THC). THC-COOH and its glucuronide conjugate have been identified as the majorend-products of metabolism. THC is highly lipid soluble, resulting in its concentration and prolongedretention in fat tissue.(3) Cannabinoids cross the placenta, but a dose-response relationship orcorrelation has not been established between the amount of marijuana use in pregnancy and the levels ofcannabinoids found in meconium, the first fecal matter passed by the neonate.(4,5) The disposition ofdrug in meconium is not well understood. The proposed mechanism is that the fetus excretes drug intobile and amniotic fluid. Drug accumulates in meconium either by direct deposition from bile or throughswallowing amniotic fluid.(5) The first evidence of meconium in the fetal intestine appears atapproximately the 10th to 12th week of gestation, and slowly moves into the colon by the 16th week ofgestation.(6) Therefore, the presence of drugs in meconium has been proposed to be indicative of inutero drug exposure during the final 4 to 5 months of pregnancy, a longer historical measure than ispossible by urinalysis.(5) Chain of custody is a record of the disposition of a specimen to document whocollected it, who handled it, and who performed the analysis. When a specimen is submitted in thismanner, analysis will be performed in such a way that it will withstand regular court scrutiny.

Useful For: Detection of in utero drug exposure up to 5 months before birth Chain of custody isrequired whenever the results of testing could be used in a court of law. Its purpose is to protect therights of the individual contributing the specimen by demonstrating that it was under the control ofpersonnel involved with testing the specimen at all times; this control implies that the opportunity forspecimen tampering would be limited. Since the evidence of illicit drug use during pregnancy can because for separating the baby from the mother, a complete chain of custody ensures that the test resultsare appropriate for legal proceedings.

Interpretation: The presence of 11-nor-delta-9-tetrahydrocannabinol-9-carboxylic acid > or =10ng/g is indicative of in utero drug exposure up to 5 months before birth.

Reference Values: Negative Positives are reported with a quantitative LC-MS/MS result. Cutoff concentrations Tetrahydrocannabinol carboxylic acid (marijuana metabolite) by LC-MS/MS: 10 ng/g

Clinical References: 1. Huestis MA: Marijuana. In Principles of Forensic Toxicology. Secondedition. Edited by B Levine. Washington DC, AACC Press, 2003 pp 229-264 2. O'Brein CP: Drugaddiction and drug abuse. In Goodman and Gilman's The Pharmacological Basis of Therapeutics. 11thedition. Edited by LL Burton, JS Lazo, KL Parker. McGraw-Hill Companies Inc, 2006. Available atURL: www.accessmedicine.com/content.aspx?aID=941547 3. Baselt RC: Tetrahydrocannabinol. InDisposition of Toxic Drugs and Chemical in Man. Edited by RC Baselt. Foster City, CA, BiomedicalPublications, 2008: pp1513-1518 4. Ostrea EM Jr, Knapop DK, Tannenbaum L, et al: Estimates ofillicit drug use during pregnancy by maternal interview, hair analysis, and meconium analysis. J Pediatr2001;138:344-348 5. Ostrea EM Jr, Brady MJ, Parks PM, et al: Drug screening of meconium in infantsof drug-dependent mothers: an alternative to urine testing. J Pediatr 1989;115:474-477 6. Ahanya SN,


Lakshmanan J, Morgan BL, Ross MG: Meconium passage in utero: mechanisms, consequences, andmanagement. Obstet Gynecol Surv 2005;60:45-56

THCM84284

11-nor-Delta-9-Tetrahydrocannabinol-9-Carboxylic Acid(Carboxy-THC) Confirmation, MeconiumClinical Information: Marijuana and other psychoactive products obtained from the plant Cannabissativa are the most widely used illicit drugs in the world.(1) Marijuana has unique behavioral effects thatinclude feelings of euphoria and relaxation, altered time perception, impaired learning and memory, lackof concentration, and mood changes (eg, panic reactions and paranoia). Cannabis sativa producesnumerous compounds collectively known as cannabinoids including delta-9-tetrahydrocannabinol (THC),which is the most prevalent and produces most of the characteristic pharmacological effects of smokedmarijuana.(2) THC undergoes rapid hydroxylation by the cytochrome (CYP) enzyme system to form theactive metabolite 11-hydroxy-THC. Subsequent oxidation of 11-hydroxy-THC produces the inactivemetabolite 11-nor-delta-9-tetrahydrocannabinol-9-carboxylic acid (THC-COOH; carboxy-THC).THC-COOH and its glucuronide conjugate have been identified as the major end-products of metabolism.THC is highly lipid soluble, resulting in its concentration and prolonged retention in fat tissue.(3)Cannabinoids cross the placenta, but a dose-response relationship or correlation has not been establishedbetween the amount of marijuana use in pregnancy and the levels of cannabinoids found in meconium, thefirst fecal matter passed by the neonate.(4,5) The disposition of drug in meconium is not well understood.The proposed mechanism is that the fetus excretes drug into bile and amniotic fluid. Drug accumulates inmeconium either by direct deposition from bile or through swallowing amniotic fluid.(5) The firstevidence of meconium in the fetal intestine appears at approximately the tenth to twelfth week ofgestation, and slowly moves into the colon by the sixteenth week of gestation.(6) Therefore, the presenceof drugs in meconium has been proposed to be indicative of in utero drug exposure during the final 4 to 5months of pregnancy, a longer historical measure than is possible by urinalysis.(5)

Useful For: Detection of in utero drug exposure to marijuana (tetrahydrocannabinol) up to 5 monthsbefore birth

Interpretation: The presence of 11-nor-delta-9-tetrahydrocannabinol-9-carboxylic acid at 10 ng/g orgreater is indicative of in utero drug exposure up to 5 months before birth.

Reference Values: Negative Positives are reported with a quantitative LC-MS/MS result. Cutoff concentrations Tetrahydrocannabinol carboxylic acid (marijuana metabolite) by LC-MS/MS: 10 ng/g

Clinical References: 1. Huestis MA: Marijuana. In Principles of Forensic Toxicology. Secondedition. Edited by B Levine. Washington DC, AACC Press, 2003 pp 229-264 2. O'Brein CP: Drugaddiction and drug abuse. In Goodman and Gilman's The Pharmacological Basis of Therapeutics. 11thedition. Edited by LL Burton, JS Lazo, KL Parker. McGraw-Hill Companies Inc, 2006. Available atURL: www.accessmedicine.com/content.aspx?aID=941547 3. Baselt RC: Tetrahydrocannabinol. InDisposition of Toxic Drugs and Chemical in Man. Edited by RC Baselt. Foster City, CA, BiomedicalPublications, 2008: pp1513-1518 4. Ostrea EM Jr, Knapop DK, Tannenbaum L, et al: Estimates of illicitdrug use during pregnancy by maternal interview, hair analysis, and meconium analysis. J Pediatr2001;138:344-348 5. Ostrea EM Jr, Brady MJ, Parks PM, et al: Drug screening of meconium in infants ofdrug-dependent mothers: an alternative to urine testing. J Pediatr 1989;115:474-477 6. Ahanya SN,Lakshmanan J, Morgan BL, Ross MG: Meconium passage in utero: mechanisms, consequences, andmanagement. Obstet Gynecol Surv 2005;60:45-56

F143P75516

14-3-3 eta ProteinClinical Information: The 14-3-3 protein appears to contribute to the pathologic process of jointerosion and, as such, is an emerging biomarker of joint damage in rheumatoid arthritis (RA) and psoriatic


arthritis. Concentrations are significantly higher in people with active joint disease than in those withinactive RA or psoriasis without arthritis. Measurement of 14-3-3 complements RF and CCP antibodytests and may improve diagnostic sensitivity.

Reference Values:

Reference Values: Normal: < or =2.0 ng/mL Elevated: >2.0 ng/mL

Clinical References: 1. Day IN, Thompson RJ: Levels of immunoreactive aldolase C, creatinekinase-BB, neuronal and non-neuronal enolase, and 14-3-3 protein in circulating human blood cells. ClinChim Acta 1984;136:219-228 2. Collins S, Boyd A, Fletcher A, et al: Creutzfeldt-Jakob disease:diagnostic utility of 14-3-3 protein immunodetection in cerebrospinal fluid. J Clin Neurosci2000;7:203-208 3. Collins S, Boyd A, Fletcher A, et al: Creutzfeldt-Jakob disease: diagnostic utility of14-3-3 protein immunodetection in cerebrospinal fluid. Clin Neuroscience 2000;7:203-208 4. BurkhardPR, Sanchez JC, Landis T, et al: CSF detection of the 14-3-3 protein in unselected patients with dementia.Neurology 2001;56:1528-1533 5. Aksamit AJ, Preissner CM, Homburger HA: Quantitation of 14-3-3 andneuron-specific enolase proteins in CSF in Creutzfeldt-Jakob disease. J Neurol 2001;57:728-730 6.Castellani RJ, Colucci M, Xie Z, et al: Sensitivity of 14-3-3 protein test varies in subtypes of sporadicCreutzfeldt-Jakob disease. Neurology 2004;63:436-442

17OHP81151

17-Hydroxypregnenolone, SerumClinical Information: Congenital adrenal hyperplasia (CAH) is caused by inherited defects in steroidbiosynthesis. Deficiencies in several enzymes cause CAH including 21-hydroxylase (CYP21A2mutations; 90% of cases), 11-hydroxylase (CYP11A1 mutations; 5%-8%), 3-beta-hydroxy dehydrogenase(HSD3B2 mutations;

dehydroepiandrosterone (DHEA) levels will be increased. In the much less common CYP11A1 mutation,androstenedione levels are elevated to a similar extent as in CYP21A2 mutation, and cortisol is also low,but OHPG is only mildly, if at all, elevated. In the also very rare 17-alpha-hydroxylase deficiency,androstenedione, all other androgen-precursors (17-alpha-hydroxypregnenolone, OHPG,dehydroepiandrosterone sulfate), androgens (testosterone, estrone, estradiol), and cortisol are low, whileproduction of mineral corticoid and its precursors (in particular pregnenolone, 11-dexycorticosterone,corticosterone, and 18-hydroxycorticosterone) are increased. See Steroid Pathways in Special Instructions.

Reference Values: CHILDREN* Males Premature (26-28 weeks): 1,219-9,799 ng/dL Premature (29-36 weeks): 346-8,911 ng/dL Full term (1-5 months): 229-3,104 ng/dL 6 months-364 days: 221-1,981 ng/dL 1-2 years: 35-712 ng/dL 3-6 years:

nonclassical congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Clin Endocrinol2000;52(5):601-607 4. Kao P, Machacek DA, Magera MJ, at al: Diagnosis of adrenal corticaldysfunction by liquid chromatography-tandem mass spectrometry. Ann Clin Lab Sci2001;31(2):199-204 5. Sciarra F, Tosti-Croce C, Toscano V: Androgen-secreting adrenal tumors.Minerva Endocrinol 1995;20(1):63-68 6. Collett-Solberg PF: Congenital adrenal hyperplasia: fromgenetics and biochemistry to clinical practice, part I. Clin Pediatr 2001:40(1):1-16

OHPG9231

17-Hydroxyprogesterone, SerumClinical Information: Congenital adrenal hyperplasia (CAH) is caused by inherited defects in steroidbiosynthesis. The resulting hormone imbalances with reduced glucocorticoids and mineralocorticoids andelevated 17-hydroxyprogesterone (OHPG) and androgens can lead to life-threatening, salt-wasting crisisin the newborn period and incorrect gender assignment of virtualized females. Adult-onset CAH mayresult in hirsutism or infertility in females. The adrenal glands, ovaries, testes, and placenta produceOHPG. It is hydroxylated at the 11 and 21 position to produce cortisol. Deficiency of either 11- or21-hydroxylase results in decreased cortisol synthesis, and feedback inhibition of adrenocorticotropichormone (ACTH) secretion is lost. Consequent increased pituitary release of ACTH increases productionof OHPG. But, if 17-alpha-hydroxylase (which allows formation of OHPG from progesterone) or3-beta-hydroxysteroid dehydrogenase type 2 (which allows formation of 17-hydroxyprogesteroneformation from 17-hydroxypregnenolone) are deficient, OHPG levels are low with possible increase inprogesterone or pregnenolone respectively. OHPG is bound to both corticosteroid binding globulin andalbumin and total OHPG is measured in this assay. OHPG is converted to pregnanetriol, which isconjugated and excreted in the urine. In all instances, more specific tests are available to diagnosedisorders or steroid metabolism than pregnanetriol measurement. Most (90%) cases of CAH are due tomutations in the steroid 21-hydroxylase gene (CYP21A2). CAH due to 21-hydroxylase deficiency isdiagnosed by confirming elevations of OHPG and androstenedione (ANST / Androstenedione, Serum)with decreased cortisol (CINP / Cortisol, Serum, LC-MS/MS). By contrast, in 2 less common forms ofCAH, due to 17-hydroxylase or 11-hydroxylase deficiency, OHPG and androstenedione levels are notsignificantly elevated and measurement of progesterone (PGSN / Progesterone, Serum) anddeoxycorticosterone (FDOC / Deoxycorticosterone [DOC], Serum), respectively, are necessary fordiagnosis. CAH21 / Congenital Adrenal Hyperplasia (CAH) Profile for 21-Hydroxylase Deficiencyallows the simultaneous determination of OHPG, androstenedione, and cortisol. See Steroid Pathways inSpecial Instructions.

Useful For: The analysis of 17-hydroxyprogesterone (17-OHPG) is 1 of the 3 analytes along withcortisol and androstenedione, that constitutes the best screening test for congenital adrenal hyperplasia(CAH), caused by either 11- or 21-hydroxylase deficiency. Analysis for 17-OHPG is also useful as part ofa battery of tests to evaluate females with hirsutism or infertility; both can result from adult-onset CAH

Interpretation: Diagnosis and differential diagnosis of congenital adrenal hyperplasia (CAH) alwaysrequires the measurement of several steroids. Patients with CAH due to steroid 21-hydroxylase gene(CYP21A2) mutations usually have very high levels of androstenedione, often 5- to 10-fold elevations.17-hydroxyprogesterone (OHPG) levels are usually even higher, while cortisol levels are low orundetectable. All 3 analytes should be tested. In the much less common CYP11A1 mutation,androstenedione levels are elevated to a similar extent as in CYP21A2 mutation, and cortisol is also low,but OHPG is only mildly, if at all, elevated. In the also very rare 17-alpha-hydroxylase deficiency,androstenedione, all other androgen-precursors (17-alpha-hydroxypregnenolone, OHPG,dehydroepiandrosterone sulfate), androgens (testosterone, estrone, estradiol), and cortisol are low, whileproduction of mineral corticoid and its precursors, in particular progesterone, 11-deoxycorticosterone, and18-hydroxycorticosterone, are increased. The goal of CAH treatment is normalization of cortisol levelsand ideally also of sex-steroid levels. Traditionally, OHPG and urinary pregnanetriol or total ketosteroidexcretion are measured to guide treatment, but these tests correlate only modestly with androgen levels.Therefore, androstenedione and testosterone should also be measured and used to guide treatmentmodifications. Normal prepubertal levels may be difficult to achieve, but if testosterone levels are withinthe reference range, androstenedione levels of up to 100 ng/dL are usually regarded as acceptable. SeeSteroid Pathways in Special Instructions.


Reference Values: Children Preterm infants Preterm infants may exceed 630 ng/dL, however, it is uncommon to see levels reach 1,000 ng/dL. Term infants 0-28 days:

differentiation from pure astrocytomas to support the presence of oligodendroglialdifferentiation/lineage Indicated when a diagnosis of oligodendroglioma, both low-grade World HealthOrganization (WHO, grade II) and anaplastic (WHO, grade III) is rendered Strongly recommendedwhen a diagnosis of mixed oligoastrocytomas is rendered

Interpretation: The presence of 1p deletion and combined 1p and 19q deletion supports a diagnosis ofoligodendroglioma may indicate that the patient may respond to chemotherapy and radiation therapy. Thepresence of gain of chromosome 19 supports a diagnosis of high-grade astrocytoma (glioblastomamultiforme). A negative result does not exclude a diagnosis of oligodendroglioma or high-gradeastrocytoma.

Reference Values: An interpretive report will be provided.

Clinical References: 1. Eckel-Passow JE, Lachance DH, Molinaro AM, et al: Glioma Groups Basedon 1p/19q, IDH, and TERT Promoter Mutations in Tumors. N Engl J Med 2015 Jun25;372(26):2499-2508 2. James CD, Smith JS, Jenkins RB: Genetic and molecular basis of primarycentral nervous system tumors. In Cancer in the Nervous System. Edited by VA Levine. New York,Oxford University Press, 2002, pp 239-251 3. Cairncross JG, Ueki K, Zlatescu MC, et al: Specific geneticpredictors of chemotherapeutic response and survival in patients with anaplastic oligodendrogliomas. JNatl Cancer Inst 1998 October 7;90(19):1473-1479 4. Ino Y, Zlatescu MC, Sasaki H, et al: Long survivaland therapeutic responses in patients with histologically disparate high-grade gliomas demonstratingchromosome 1p loss. J Neurosurg 2000 June;92(6):983-990 5. Smith JS, Tachibana I, Passe SM, et al:PTEN mutation, EGFR amplification, and outcome in patients with anaplastic astrocytoma andglioblastoma multiforme. J Natl Cancer Inst 2001 August 15;93(16):1246-1256 6. Smith JS, Alderete B,Minn Y, et al: Localization of common deletion regions on 1p and 19q in human gliomas and theirassociation with histological subtype. Oncogene 1999 July 15;18(28):4144-4152 7. Smith JS, Perry A,Borell TJ, et al: Alterations of chromosome arms 1p and 19q as predictors of survival inoligodendrogliomas, astrocytomas, and mixed oligoastrocytomas. J Clin Oncol 2000February;18(3):636-645 8. Jenkins RB, Curran W, Scott CB, et al: Pilot evaluation of 1p and 19qdeletions in anaplastic oligodendrogliomas collected by a national cooperative cancer treatment group.Am J Clin Oncol 2001 October;24(5):506-508 9. Burger PC: What is an oligodendroglioma? Brain Pathol2002;12:257-259

BPGMM63208

2,3-Bisphosphoglycerate Mutase, Full Gene SequencingAnalysis, VariesClinical Information: Erythrocytosis (ie, increased RBC mass and elevated hemoglobin andhematocrit) may be primary, due to an intrinsic defect of bone marrow stem cells as in polycythemia vera(PV), or secondary, in response to increased serum erythropoietin (Epo) levels. Secondary erythrocytosisis associated with a number of disorders including chronic lung disease, chronic increase in carbonmonoxide, cyanotic heart disease, high-altitude living, renal cysts and tumors, hepatoma, and otherEpo-secreting tumors. When these common causes of secondary erythrocytosis are excluded, a heritablecause involving hemoglobin or erythrocyte regulatory mechanism may be suspected. Unlike PV,hereditary erythrocytosis is not associated with the risk of clonal evolution and most commonly presentsas isolated erythrocytosis that has been present since childhood. Hereditary erythrocytosis may be causedby mutations in one of several genes and inherited in either an autosomal dominant or autosomal recessivemanner. Genetic mutations causing hereditary erythrocytosis have been found in genes coding for alphaand beta hemoglobins, hemoglobin stabilization proteins (eg, 2,3-bisphosphoglycerate mutase: BPGM),the erythropoietin receptor (EPOR), and oxygen-sensing pathway enzymes (hypoxia-inducible factor:HIF, prolyl hydroxylase domain: PHD, and von Hippel Lindau: VHL), see table. High-oxygen-affinityhemoglobin variants and BPGM abnormalities result in a decreased p50 result, whereas those affectingEPOR, HIF, PHD, and VHL have normal p50 results. The true prevalence of mutations causing hereditaryerythrocytosis is unknown; however, very few cases of 2,3-BPG deficiency-associated hereditaryerythrocytosis have been identified and this disorder is thought to be rare. Erythrocytosis Testing GeneInheritance Serum Epo p50 JAK2 V617F Acquired Decreased Normal JAK2 exon 12 Acquired


Decreased Normal EPOR Dominant Decreased Normal PHD2/EGLN1 Dominant Normal Normal tomildly decreased BPGM Recessive Normal Decreased Beta Globin Dominant Normal to increasedDecreased Alpha Globin Dominant Normal to increased Decreased HIF2A/EPAS1 Dominant Normal toincreased Normal VHL Recessive Normal to increased Normal

Useful For: Diagnosis of 2,3-bisphosphoglycerate mutase deficiency in individuals with lifelong,unexplained erythrocytosis Identifying mutation carriers in family members of an affected individual forthe purposes of preconception genetic counseling

Interpretation: An interpretive report will be provided and will include specimen information, assayinformation, and whether the specimen was positive for any mutations in the gene. If positive, themutation will be correlated with clinical significance, if known.


Clinical References: 1. Petousi N, Copley RR, Lappin TR, et al: Erythrocytosis associated with anovel missense mutation in the BPGM gene. Haematologica 2014 Oct;99:e201-e204 2. Hoyer JD, AllenSL, Beutler E, et al: Erythrocytosis due to bisphosphoglycerate mutase deficiency with concurrentglucose-6-phosphate dehydrogenase (G-6-PD) deficiency. Am J Hematol 2004;75(4):205-208 3. RosaR, Prehu MO, Beuzard Y, Rosa J: The first case of a complete deficiency of diphosphoglycerate mutasein human erythrocytes. J Clin Invest 1978;62(5):907-915

23BPG37931

2,3-Dinor-11Beta-Prostaglandin F2 Alpha, UrineClinical Information: 2,3-Dinor-11beta-prostaglandin F2 alpha is the most abundant metabolicproduct of prostaglandins released by activated mast cells. Systemic mastocytosis (SM) is a disease inwhich clonally derived mast cells accumulate in peripheral tissues. Degranulation of these mast cellsreleases large amounts of histamines, prostaglandins, leukotrienes, and tryptase. Â The World HealthOrganization diagnostic criteria for SM require the presence of elevated mast cell counts on a bonemarrow biopsy and 1 of the following minor criteria: abnormal mast cell morphology, KIT Asp816Valmutation, CD25-positive mast cells, or serum tryptase greater than 20 ng/mL. Alternatively, SMdiagnosis can be made with the presence of 3 minor criteria in the absence of abnormal bone marrowstudies. Measurement of mast cell mediators in blood or urine is less invasive and is advised for theinitial evaluation of suspected cases. Elevated levels of serum tryptase, urinary N-methylhistamine(NMH), 2,3-dinor-11beta-prostaglandin F2 alpha (2,3 BPG), or leukotriene E4 (LTE4) are consistentwith the diagnosis of systemic mast cell disease.

Useful For: Screening for mast cell activation disorders including systemic mastocytosis

Interpretation: Urinary 2,3-dinor-11beta-prostaglandin F2 alpha (2,3-BPG) values above 3,263pg/mg creatinine are consistent with, but not necessarily diagnostic of, systemic mastocytosis. Valuesshould be interpreted in the context of clinical presentation and additional mast cell disease markers(serum tryptase, urinary N-methyl histamine, and/or urinary leukotriene E4).

Reference Values:

21DOC89477

21-Deoxycortisol, SerumClinical Information: The adrenal glands, ovaries, testes, and placenta produce steroid hormones,which can be subdivided into 3 major groups: mineral corticoids, glucocorticoids, and sex steroids.Synthesis proceeds from cholesterol along 3 parallel pathways, corresponding to these 3 major groups ofsteroids, through successive side-chain cleavage and hydroxylation reactions. At various levels of eachpathway, intermediate products can move into the respective adjacent pathways via additional,enzymatically catalyzed reactions (see Steroid Pathways in Special Instructions). 21-Deoxycortisol is anintermediate steroid in the glucocorticoid pathway. While the main substrate flow in glucocorticoidsynthesis proceeds from 17-hydroxyprogesterone via 21-hydroxylation to 11-deoxycortisol and then,ultimately, to cortisol, a small proportion of 17-hydroxyprogesterone is also hydroxylated at carbonnumber 11 by 11-beta-hydroxylase 1 (CYP11B1), yielding 21-deoxycortisol. This in turn can also serveas a substrate for 21-hydroxylase (CYP21A2), resulting in formation of cortisol. The major diagnosticutility of measurements of steroid synthesis intermediates lies in the diagnosis of disorders of steroidsynthesis, in particular congenital adrenal hyperplasia (CAH). All types of CAH are associated withcortisol deficiency with the exception of CYP11B2 deficiency and isolated impairments of the 17-lyaseactivity of CYP17A1 (this enzyme also has 17-alpha-hydroxylase activity). In case of severe illness ortrauma, CAH predisposes patients to poor recovery or death. Patients with the most common form ofCAH (21-hydroxylase deficiency, >90% of cases), with the third most common form of CAH(3-beta-steroid dehydrogenase deficiency,

21-Hydroxycortisol measurements are particularly useful in equivocal cases of suspected 21-hydroxylasedeficiency. Most untreated patients with 21-hydroxylase deficiency have serum 17-hydroxyprogesteroneconcentrations well in excess of 1,000 ng/dL. For the few patients with levels in the range of greater than630 ng/dL (upper limit of reference range for newborns) to 2,000 ng/dL or 3,000 ng/dL, it might beprudent to consider 11-hydroxylase deficiency as an alternative diagnosis. This is particularly true ifserum androstenedione concentrations are also only mildly-to-modestly elevated, and if the phenotype isnot salt wasting but either simple virilizing (female) or normal (female or male). 11-Hydroxylasedeficiency, in particular if it affects 11 beta-hydroxylase 1 (CYP11B1), can be associated with modestelevations in serum 17-hydroxyprogesterone concentrations. In these cases testing for CYP11B1deficiency and 11 beta-hydroxylase 2 (CYP11B2) deficiency should be considered and interpreted asdescribed above. Alternatively, measurement of 21-deoxycortisol might be useful in such cases. Thisminor pathway metabolite accumulates in CYP21A2 deficiency, as it requires 21-hydroxylation to beconverted to cortisol, but is usually not elevated in CYP11B1 deficiency, since its synthesis requires via11-hydroxylation of 17-hydroxyprogesterone. For genetic counseling purposes, identification ofasymptomatic carriers of CYP21A2 mutations and deletions is sometimes required. The gold-standard isfull DNA sequencing of CYP21A2, its pseudogene CYP21A1P, and, if possible, recombinants of geneand pseudogene, along with deletion detection. Such a procedure is costly and complex, and often has aslow turnaround time. Therefore, many laboratories perform less complex, but also less complete,mutation and deletion assessments, which may miss a significant minority of heterozygote carriers.Biochemical testing using adrenocorticotropic hormone (ACTH) ACTH1-24 adrenal stimulationrepresents an alternative. However, for 17-hydroxyprogesterone and androstenedione measurements thereis significant overlap between poststimulation results in normals and in heterozygote carriers. By contrast,poststimulation 21-deoxycortisol concentrations of 55 ng/dL identify virtually all heterozygote carriers,with minimal overlap with normal subjects. The goal of congenital adrenal hyperplasia (CAH) treatmentis normalization of cortisol levels and ideally also of sex steroid levels. Serum 17-hydroxyprogesterone,androstenedione, and testosterone should be measured and used to guide treatment modifications. Normalprepubertal androgen levels may be difficult to achieve, but if testosterone levels are within the referencerange, androstenedione levels up to 100 ng/dL are usually regarded as acceptable.17-Hydroxyprogesterone levels should not significantly exceed the normal reference range at any time ofthe day. However, during puberty, the changing levels of sex steroid production may make17-hydroxyprogesterone measurements less reliable. Since 21-deoxycortisol is not a sex-steroid precursor,its levels appear more reliable during the pubertal period, again, the aim being not to exceed the referencerange significantly.

Reference Values:

diseases that together comprise Type I or Type II autoimmune polyglandular syndrome (APS).Antibodies that react with several steroidogenic enzymes (most often 21-hydroxylase) are present in theserum of up to 86% of patients with autoimmune primary adrenal insufficiency, but only rarely inpatients with other causes of adrenal insufficiency. Therefore, anti-21-hydroxylase autoantibodies(21-OH Abs) are markers of autoimmune Addison disease, whether itâ€™s present alone, or as part ofType I or Type II APS. The measurement of 21-OH Abs is an important step in the investigation ofadrenal insufficiency, and may also aid in the detection of those at risk of developing autoimmuneadrenal failure in the future.

Useful For: Investigation of adrenal insufficiency Aid in the detection of those at risk of developingautoimmune adrenal failure in the future

Interpretation: This is a qualitative test. A positive result indicates the presence of autoantibodies to21-hydroxylase and is consistent with Addison disease. Utilizing an index value of

highly homologous pseudogene, CYP21A1P (transcriptionally inactive). In particular, partial or complexrearrangements (with or without accompanying gene duplication events), which lead to reciprocalexchanges between gene and pseudogene, can present severe diagnostic challenges. Comprehensivegenetic testing strategies must therefore allow accurate assessment of most, or all, known rearrangementsand mutations, as well as unequivocal determination of whether the observed changes are located within apotentially transcriptionally active genetic segment. Testing of additional family members is often neededfor clarification of genetic test results.

Useful For: Carrier screening and diagnosis of 21-hydroxylase deficient congenital adrenalhyperplasia (CAH) in individuals with a personal or family history of 21-hydroxylase deficiency, or asfollow-up to positive CAH newborn screens and/or measurement of basal and adrenocorticotropichormone- 1-24 stimulated 17-hydroxyprogesterone, androstenedione, and other adrenal steroid levelsMay be used to identify CYP21A2 mutations in individuals with a suspected diagnosis of21-hydroxylase deficient CAH when a common mutation panel is negative or only identifies 1mutation. In prenatal cases of ambiguous genitalia detected by ultrasound, particularly when the fetus isconfirmed XX female by chromosome analysis. This test ID should also be used for known/familialvariant analysis for CYP21A2. Due to the complexity of the CYP21A2 locus, site specific testing forknown/familial variants is not offered for this gene.

Interpretation: All detected alterations will be evaluated according to American College of MedicalGenetics and Genomics (ACMG) recommendations. Variants will be classified based on known,predicted, or possible pathogenicity and reported with interpretive comments detailing their potential orknown significance.


Clinical References: 1. Richards S, Aziz N, Bale S, et al: Standards and guidelines for theinterpretation of sequence variants: a joint consensus recommendation of the American College ofMedical Genetics and Genomics and the Association for Molecular Pathology. Genet Med 2015May;17(5):405-424 2. Collett-Solberg PF: Congenital adrenal hyperplasias: from clinical genetics andbiochemistry to clinical practice, part I. Clin Pediatr 2001;40:1-16 3. Mercke DP, Bornstein SR, AvilaNA, Chrousos GP: NIH conference: future directions in the study and management of congenitaladrenal hyperplasia due to 21-hydroxylase deficiency. Ann Intern Med 2002;136:320-334 4. SpeiserPW, White PC: Medical progress: congenital adrenal hyperplasia. N Engl J Med 2003;349:776-788

DD22F35246

22q11.2 Deletion/Duplication, FISHClinical Information: The 22q deletion syndrome and 22q duplication syndrome have overlappingphenotypes. Deletions of 22q are associated with DiGeorge and velocardiofacial syndrome. Thesesyndromes are manifested by the presence of growth deficiency, global developmental delay, heartdefect, and hearing loss. The major birth defects include palatal clefting or insufficiency and thymusaplasia. Prominent facial features are widely spread eyes, superior placement of eyebrows, downwardslanting palpebral fissures with or without ptosis (droopy upper eyelid), mild micrognathia (small jaw),and a long, narrow face. FISH studies are highly specific and do not exclude other chromosomeabnormalities.

Useful For: Establishing a diagnosis of 22q deletion/duplication syndromes Detecting crypticrearrangements involving 22q11.2 or 22q11.3 that are not demonstrated by conventional chromosomestudies

Interpretation: Any individual with a normal signal pattern in each metaphase is considerednegative for this probe. Any patient with a FISH signal pattern indicating loss of the critical region (1signal) will be reported as having a deletion of

rochester 2020 interpretive handbook · 2020-01-03 · and are not necessarily correct....

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