Alcohol Biomarkers - Proper use and interpretation
2012 SAMHSA advisory warning regarding false-positive tests
from extrensic ethanol exposure
Proper use of alcohol markers EtG and EtS in forensic settings.
from extrensic ethanol exposure
Proper use of alcohol markers EtG and EtS in forensic settings.
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For additional consultation or information regarding EtG/EtS testing contact Gregory Skipper, MD at
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Facts about EtG/EtS testing:
History
Ethylglucuronide (EtG) was described as early as the 1950's, however, clinical use of the test as an alcohol marker began in 2001 when Dr. Friedrich Wurst, in Switzerland, and Dr. Gregory Skipper, in the USA reported a study of alcoholics in a psychiatric facility in Germany. Their findings demonstrated that EtG was a more sensitive and reliable indicator of both drinking and abstinence than was urine alcohol. Dr. Skipper recognized that urine EtG would be a valuable test in monitoring professionals. The Federation of State Physician Health Programs estimates that over 9,000 physicians are in monitoring in the USA and a majority have abused alcohol. An essential issue in justifying the continued safe practice of recovering physicians involves the ability to reliably document their abstinence.
As EtG and EtS testing gained wider use, several important issues began to emerge that frame the complexities of interpreting these tests. It's important to understand their limitations, as with all tests, to use them properly. Some of these issues are discussed in more depth elsewhere on this site and include:
Ethylglucuronide (EtG) was described as early as the 1950's, however, clinical use of the test as an alcohol marker began in 2001 when Dr. Friedrich Wurst, in Switzerland, and Dr. Gregory Skipper, in the USA reported a study of alcoholics in a psychiatric facility in Germany. Their findings demonstrated that EtG was a more sensitive and reliable indicator of both drinking and abstinence than was urine alcohol. Dr. Skipper recognized that urine EtG would be a valuable test in monitoring professionals. The Federation of State Physician Health Programs estimates that over 9,000 physicians are in monitoring in the USA and a majority have abused alcohol. An essential issue in justifying the continued safe practice of recovering physicians involves the ability to reliably document their abstinence.
As EtG and EtS testing gained wider use, several important issues began to emerge that frame the complexities of interpreting these tests. It's important to understand their limitations, as with all tests, to use them properly. Some of these issues are discussed in more depth elsewhere on this site and include:
- Incidental Exposure: Claims of "false positive EtG tests" from incidental exposure to alcohol began to occur. An online registry was developed for those who claimed they'd been falsely accused of drinking. This phenomenon of incidental or extraneous exposure to alcohol is very similar to the phenomenon of poppy seeds causing positive tests for morphine and is discussed in more depth in a separate section of this website. A factor that makes incidental exposure to alcohol a concern is that there are literally thousands of items used every day that contain ethanol and exposure can occur from multiple sources and can be additive.
- Elevated Concentration of Urine Artificially Increases EtG and EtS (and other analyte) levels: Because determination regarding the possibility of incidental exposure is in part inferred by the concentration of EtG and/or EtS (i.e., higher levels are more likely due to alcoholic beverage consumption) it is very important to consider the effects of concentration on reported levels. Few labs automatically adjust or correct ("normalize") EtG or EtS levels for concentration. Urine creatinine has traditionally been used as a measure of concentration. The higher the creatinine the more concentrated the urine. Therefore, to adjust for the effect of concentration one can apply the same multiplier times EtG and/or EtS as would be used to reduce or increase creatinine to a given level. The standard most often used is a creatinine of 100mg/dl. For example, if urine EtG is reported at 2,000ng/ml and the urine creatinine is 400mg/dl the U100EtG would be 500ng/ml because the mulitplier of 1/4th would be needed to reduce the creatinine to 100 and 1/4 times 2000 equals 500. The actual formula is U100EtG = 100/Urine Creatinine x Urine EtG. Obviously normalizing reported values to adjust for concentration can make significant changes and are important to consider, especially for lower levels of EtG/EtS.
- Variation in amount of EtG produced for a given exposure to alcohol: There appears to be significant intersubject variation in the amount of EtG produced from a given exposure to alcohol. This is quit evident in exposure studies. Levels of EtG can vary dramatically between individuals who consume the same amount of alcohol, sometimes as much as 200 fold. This is important to keep in mind. This means that any study designed to assess EtG levels will need a large population of test subjects. Many reports regarding EtG levels have been from studies with very few subjects making them suspect as representing the entire population.
- No Cutoff Known that Distinguishes Between Incidental Exposure and Drinking Alcohol: There is no known level of EtG or EtS which if exceeded proves drinking. It is logical to assume that higher levels are more likely to be from drinking but there is no "bright line" that can distinguish between drinking and incidental exposure. SAMHSA guidelines state that an EtG level over 1,000ng/ml is likely due to drinking.
- Informed Consent: Individuals being tested with EtG and/or EtS should be thoroughly and carefully informed regarding items to avoid. A statement or contract addendum can be useful. (Download sample addendum used by some drug courts.) Even with this it is extremely difficult to avoid all sources of ethanol.
- Topical Alcohol as a Source of Incidental Exposure: Volunteer exposure trials have demonstrated that alcohol-based handsanitizing gel causes positive EtG/EtS tests. A surprise finding has been that alcohol absorbed through inhalation of vapor, rather than through skin, is the chief cause of these positives EtG and EtS levels.
- Stability and Synthesis of EtG: It was known that EtG could occasionally disappear (or be degraded) in urine stored at room temperature but not if frozen or heated. Researchers in Scandinavia further clarified this phenomenon when they reported that EtG (but not EtS) could be degraded in urine due to certain bacteria (explaining why heating or cooling samples, which would inhibit bacterial activity, resulted in less degradation). Furthermore, they then reported that in the presence of alcohol (fermented or added to urine) EtG but not EtS could be synthesized by bacteria in-vitro. This finding supported the likelihood that ethylsulfate (EtS) may be a superior marker in that it is more sensitive and specific.
- Reliability: Despite the possibility of incidental exposure most people who test positive for EtG actually did drink as the cause of the positive test. In one programs review, approximately 50% of individuals admitted drinking when supportively confronted. Another 40% subsequently admitted drinking at a later date. Those who initially deny drinking should receive more careful monitoring, testing, or other treatment, however, without other proof, and especially for EtG levels <1,000ng/ml, they should not be presumed to have been drinking. SAMHSA advisory warning against over reliance on a positive EtG as sole proof of drinking.)
- Auto-Brewery Syndrome: The question of whether sugar can ferment to alcohol within the body, in the GI tract, has been questioned. Recently, this question has achieved new importance as a study in Europe has shown that volunteers consuming sugar and baker's yeast orally produced elevated EtG/EtS levels.
