Test Catalog

Test Id : ORXNA

Orexin-A/Hypocretin-1, Spinal Fluid

Useful For
Suggests clinical disorders or settings where the test may be helpful

Aiding in the diagnosis and differentiation of type 1 narcolepsy from other causes of hypersomnolence


This assay is not intended for use as a screening test.


Orexin-A (hypocretin-1) is a neuropeptide involved in the sleep/wake cycle in humans. An abnormally low concentration of orexin-A (hypocretin-1) in cerebrospinal fluid (CSF) indicates type I narcolepsy.


CSF concentrations have been found to almost always be above 200 pg/mL in healthy individuals and those with non-type 1-narcoleptic sleep disorders, such as narcolepsy type 2 and idiopathic hypersomnia.

Method Name
A short description of the method used to perform the test

Radioimmunoassay (RIA)

NY State Available
Indicates the status of NY State approval and if the test is orderable for NY State clients.


Reporting Name
Lists a shorter or abbreviated version of the Published Name for a test

Orexin-A/Hypocretin-1, CSF

Lists additional common names for a test, as an aid in searching





Specimen Type
Describes the specimen type validated for testing


Ordering Guidance

Orexin-A (hypocretin-1) deficiency is the hallmark of narcolepsy type 1. The diagnostic criteria for type 1 narcolepsy include the presence of cataplexy and/or measured cerebrospinal fluid orexin-A/hypocretin-1 concentrations less than or equal to 110 pg/mL. Alternative testing for narcolepsy type 1 includes mean latency of 8 minutes in the clinical multiple sleep latency test, with evidence of sleep-onset rapid eye movement periods and cataplexy.

Specimen Required
Defines the optimal specimen required to perform the test and the preferred volume to complete testing

Patient Preparation: Patient should not have recently received radioisotopes, either therapeutically or diagnostically, due to potential assay interference.

Collection Container/Tube: Sterile vial

Submission Container/Tube: Plain vial with no additives

Specimen Volume: 1.5 mL

Pediatric Volume: 0.5 mL minimum volume

Collection Instructions:

1. Obtain aliquot from second collection vial (preferred, not required).

2. Hemolyzed specimens will give false-positive results. Specimens should be centrifuged to remove any red cells prior to shipping.


If not ordering electronically, complete, print, and send a Neurology Specialty Testing Client Test Request (T732) with the specimen.

Specimen Minimum Volume
Defines the amount of sample necessary to provide a clinically relevant result as determined by the Testing Laboratory

0.5 mL

Reject Due To
Identifies specimen types and conditions that may cause the specimen to be rejected

Gross hemolysis Reject

Specimen Stability Information
Provides a description of the temperatures required to transport a specimen to the performing laboratory, alternate acceptable temperatures are also included

Specimen Type Temperature Time Special Container
CSF Frozen 120 days

Useful For
Suggests clinical disorders or settings where the test may be helpful

Aiding in the diagnosis and differentiation of type 1 narcolepsy from other causes of hypersomnolence


This assay is not intended for use as a screening test.

Clinical Information
Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

Narcolepsy affects 0.02% to 0.05% of the population and the onset of symptoms often occurs in adolescence. Orexin (also known as orexin-A or hypocretin-1) is a neuropeptide produced in the hypothalamus and is involved in the sleep/wake cycle in humans. Impairment of orexin production and orexin-modulated neurotransmission is associated with narcolepsy with cataplexy (episodes of muscle weakness in response to emotional stimuli). An abnormally low concentration of orexin-A/hypocretin-1 in cerebrospinal fluid (CSF) is indicative of what is termed type 1 narcolepsy.


Survey of the literature reveals that approximately 85% to 95% of randomly selected individuals with type 1 narcolepsy and typical cataplexy, exhibit low (<110 pg/mL) CSF orexin (hypocretin-1) concentrations.(1) In one large study, the sensitivity of this cutoff was found to be 87% with a specificity of 99%.(2) Orexin deficiency and type 1 narcolepsy are closely associated with HLA (human leukocyte antigen) complex DQB1 *0602. It is estimated that only 1 in 500 HLA DQB1*0602-negative individuals exhibit low CSF orexin concentrations. CSF concentrations have been found to almost always be above 200 pg/mL in healthy individuals and those with non-type 1-narcoleptic sleep disorders such as narcolepsy type 2 and idiopathic hypersomnia.

Reference Values
Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

Normal individuals should be >200 pg/mL


Previous literature has defined cerebrospinal fluid orexin-A/hypocretin-1 concentrations of 110 pg/mL or below as being consistent with narcolepsy type 1-(Mignot E: Arch Neurol 2002:59;1553-1562). Concentrations between 111 to 200 pg/mL are considered intermediate and have limited diagnostic utility for narcolepsy, as they may be representative of other neurological disorders. Concentrations above 200 pg/mL are considered normal.

Provides information to assist in interpretation of the test results

The diagnostic criteria for type 1 narcolepsy in the International Classification of Sleep Disorders (3) include the presence of hypersomnia, cataplexy (episodes of muscle weakness in response to emotional stimuli) and measured cerebrospinal fluid (CSF) orexin (hypocretin-1) concentrations less than or equal to 110 pg/mL.


Orexin (hypocretin-1) CSF concentrations have been classified into 3 categories in the literature. They include low (< or =110 pg/mL), which is indicative of type 1 narcolepsy; intermediate (ranges between 111-200 pg/mL); and normal (>200 pg/mL). Previous studies have shown that 106 of 113 patients with clinically defined type 1 narcolepsy exhibited low (<110 pg/mL) orexin concentrations. In another study, all 48 healthy individuals exhibited orexin (hypocretin-1) CSF concentrations above 200 pg/mL.


In the periodic hypersomnia disorder of Kleine-Levin syndrome, the CSF orexin levels may be low during the sleepy periods, with return to normal when individuals are not sleepy.

Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

Several factors contribute in the decision to measure orexin in cerebrospinal fluid (CSF). Orexin deficiency in HLA (human leukocyte antigen) DQB1*0602-negative patients is rare. This test may be considered for the diagnosis of narcolepsy type 1, after HLA positivity is shown, if a clinical multiple sleep latency test is negative or unavailable due to potential confounding circumstances. It may also be considered if there is suspicion that cataplexy is of psychogenic origin.


Orexin (hypocretin-1) concentrations between 111 to 200 pg/mL are considered intermediate and have limited diagnostic utility for type 1 narcolepsy, as they may be representative of other neurological disorders.


This test should not be requested in patients who have recently received radioisotopes, therapeutically or diagnostically, because of potential assay interference. A recommended time period before collection cannot be made because it will depend on the isotope administered, the dose given, and the clearance rate in the individual patient.


Some patients who have been exposed to animal antigens, either in the environment or as part of treatment or imaging procedures, may have circulating anti-animal antibodies present. These antibodies may interfere with the assay reagents to produce unreliable results.

Supportive Data

In an in-house Mayo Clinic study utilizing this assay on cerebrospinal fluid (CSF) from 100 individuals without type 1 narcolepsy, all samples (100%) exhibited orexin (hypocretin-1) concentrations higher than the 200 pg/mL normal threshold (mean value of 531pg/mL + or - 89). Additionally, all 6 out of 6 patients with confirmed type 1 narcolepsy had measured CSF concentrations below 110 ng/mL by this assay (mean value of <50 pg/mL).

Clinical Reference
Recommendations for in-depth reading of a clinical nature

1. Bourgin P, Zeitzer JM, Mignot E: CSF hypocretin-1 assessment in sleep and neurological disorders. Lancet Neurol. 2008 Jul;7(7):649-662. doi: 10.1016/S1474-4422(08)70140-6

2. Mignot E, Lammers GJ, Ripley B, et al: The role of cerebrospinal fluid hypocretin measurement in the diagnosis of narcolepsy and other hypersomnias. Arch Neurol. 2002 Oct;59(10):155-162. doi: 10.1001/archneur.59.10.1553

3. Sateia MJ: International classification of sleep disorders-third edition: highlights and modifications. Chest. 2014 Nov;146(5):1387-1394. doi: 10.1378/chest.14-0970

4. Dauvilliers Y, Arnulf I, Mignot E: Narcolepsy with cataplexy. Lancet. 2007 Feb;369(9560):499-511. doi: 10.1016/S0140-6736(07)60237-2

5. Ripley B, Overeem S, Fujiki N, et al: CSF hypocretin/orexin levels in narcolepsy and other neurological conditions. Neurology. 2001 Dec 26;57(12):2253-2258. doi: 10.1212/wnl.57.12.2253

Method Description
Describes how the test is performed and provides a method-specific reference

The orexin-A (hypocretin-1) cerebrospinal fluid assay is a competitive radioimmunoassay. Orexin-A (hypocretin-1) in the patient sample competes with labeled (125)I orexin-A/hypocretin-1 for a limited number of primary antibody binding sites during a 24-hour incubation. Antibody-bound orexin-A/hypocretin-1 is separated from the unbound portion by a goat-anti-rabbit secondary antibody. Centrifugation brings down the heavy antibody complexes while unbound antigen remains in solution and is discarded. The competitive binding to the anti-peptide between endogenous orexin-A/hypocretin-1 and labeled peptide allows for the determination of orexin-A/hypocretin-1 concentration. This is done by measuring bound labeled peptide as a function of orexin-A/hypocretin-1 concentration in a prepared calibration curve.(Unpublished Mayo method)

PDF Report
Indicates whether the report includes an additional document with charts, images or other enriched information


Day(s) Performed
Outlines the days the test is performed. This field reflects the day that the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time before the test is performed. Some tests are listed as continuously performed, which means that assays are performed multiple times during the day.

Twice monthly (Second and fourth Monday)

Report Available
The interval of time (receipt of sample at Mayo Clinic Laboratories to results available) taking into account standard setup days and weekends. The first day is the time that it typically takes for a result to be available. The last day is the time it might take, accounting for any necessary repeated testing.

3 to 32 days

Specimen Retention Time
Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded

90 days

Performing Laboratory Location
Indicates the location of the laboratory that performs the test


Several factors determine the fee charged to perform a test. Contact your U.S. or International Regional Manager for information about establishing a fee schedule or to learn more about resources to optimize test selection.

  • Authorized users can sign in to Test Prices for detailed fee information.
  • Clients without access to Test Prices can contact Customer Service 24 hours a day, seven days a week.
  • Prospective clients should contact their Regional Manager. For assistance, contact Customer Service.

Test Classification
Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR) product.

This test was developed, and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the US Food and Drug Administration.

CPT Code Information
Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Clinic Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.

CPT codes are provided by the performing laboratory.


LOINC® Information
Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the order and results codes of this test. LOINC values are provided by the performing laboratory.

Test Id Test Order Name Order LOINC Value
ORXNA Orexin-A/Hypocretin-1, CSF 91670-0
Result Id Test Result Name Result LOINC Value
Applies only to results expressed in units of measure originally reported by the performing laboratory. These values do not apply to results that are converted to other units of measure.
604230 Orexin-A/Hypocretin-1, CSF 91670-0

Test Setup Resources

Setup Files
Test setup information contains test file definition details to support order and result interfacing between Mayo Clinic Laboratories and your Laboratory Information System.

Excel | Pdf

Sample Reports
Normal and Abnormal sample reports are provided as references for report appearance.

Normal Reports | Abnormal Reports

SI Sample Reports
International System (SI) of Unit reports are provided for a limited number of tests. These reports are intended for international account use and are only available through MayoLINK accounts that have been defined to receive them.

SI Normal Reports | SI Abnormal Reports