New Alcohol Markers - Proper use and interpretation


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Notice: New advisory for courts and others who wish to use EtG/EtS testing for proof of drinking!
For additional consultation or information regarding EtG/EtS testing contact Gregory Skipper, MD at
gregory.skipper@gmail.com
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 - Proper use of EtG/EtS and other alcohol markers
 - Assistance setting up monitoring for alcohol use
   (courts, boards, businesses, schools, or individuals)
 - Advice regarding false positive tests 


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. An essential issue in justifying the continued safe practice of recovering physicians involves the ability to reliably document their abstinence.

As the test 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 and listserve was developed for for those who claimed they'd been falsely accussed of drinking. The clamor of concern among this group rose rapidly and became extremely vigorous. This phenomenon of incidental exposure 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 is 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 present in urine it is very important to consider the effects of concentration on reported levels. Few labs automatically adjust or correct EtG 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 level of 20, 50 or 100 can be used. For example, if urine creatinine 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. Obviously correcting reported values to adjust for concentration can make significant changes at times and are important to consider, especially for EtG levels under 20,000ng/ml or so.
  • Variation in amount of EtG produced for a given exposure to alcohol: There appears to be significant intrasubject variation in the amount of EtG produced from a given exposure to alcohol. This is quit evident in exposure studies. Levels can vary dramatically between individuals, sometimes as much as 200 fold. This is important to keep in mind. There are likely individuals in the population that are "hyperproducers" of EtG and have much higher levels following exposure to alcohol, including incidental exposure. 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. 
  • 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 . 
  • 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 could be synthesized by bacteria in-vitro. This finding supported the likelihood that ethylsulfate (EtS), another minor metabolite of alcohol, may be a superior marker to EtG, 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, 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 GI tract has been questioned. Recently, this question has achieved new importance as a study in Europe, soon to be published, has shown that volunteers consuming sugar and baker's yeast orally produced elevated EtG/EtS levels.
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