Draft 1 urinary porphyrins

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  • Here is the reference for that article:

    Champoux L, Rodrigue J, Trudeau S, Boily MH, Spear PA, Hontela A.Ecotoxicology.(2006) Contamination and biomarkers in the great blue heron, an indicator of the state of the st. Lawrence river.Feb;15(1):83-96. Epub 2006 Jan 7.
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  • Thanks, Elena!

    Not much is out there on humans but I did find this vaguely appropriate answer:
    Herons on the St. Lawrence river were evaluated for toxicity presumed to be due to Hg and PCB exposure. They found that porphyrins (measured in plasma, actually) and thyroid hormones (among other biomarkers) were useful for following the extent of exposure and effects of the toxicity. They were 'sufficiently sensitive to reflect local and regional variations in contamination' and were somehow non-invasively measured, probably because they measured amounts in the birds eggs.
    So, to answer your question, I think that the urinary porphyrin testing may give one cause to evaluate the thyroid seeing as how Hg exposure, at minimum, effects both thyroid hormones and porphyrin production. What a novel idea!
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  • Hi, Dr. Albro! I'm wondering what other conditions would warrant porphyrin testing. For example, mercury blocks the conversion of inactive thyroid hormone T4 to the active form T3 by interfering with the binding of selenium. Could porphyrin testing be used as a way of assessing a patient's thyroid function?
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  • 1. Subject: Metametrix Porphyrins Profile – Urine<br />Autism is garnering a lot of attention in the media. Autism is dramatically increasing in incidence and is now considered an epidemic.4 There are no objective means to diagnose the disorder.4 Diagnosis is made subjectively, based on the perceived behavior of the subject.4 Nevertheless, efforts to objectify the diagnosis have been made and continue to be refined. The urinary profile test is one such objective measure. It is worth noting that this test is not limited to assessing the autistic patient, however.<br />Why use this test? Exposure to mercury can cause immune, sensory, neurological, motor and behavioral dysfunction similar to traits defining or associated with autism spectrum disorder.1 These similarities extend to neuroanatomy, neurotransmitters, and biochemistry.1 Employing a relatively affordable, available, non-invasive (and thus, relatively safe) test to indirectly determine the levels of mercury in the body is desireable.2 It is presumed that the level of kidney mercury that accounts for the output of urinary porphyrins is proportional to the level of burden in the body at large.2<br />According to the Metametrix website the Porphyrins Profile can help identify the severity of heavy metal toxicity or organic chemical exposure in patients (urinary porphyrins are affected by xenobiotics and heavy metals other than mercury).7 Chemical exposure and a heavy toxic burden can have physiological effects resulting in impaired metabolism and cellular function.7 Porphyrin testing helps identify:<br />Levels of biochemical damage caused by toxicant exposure<br />Physiologic burden of a person's level of toxins<br />Levels of porphyrin elevation correlated with levels of toxic interference<br />Toxicity of patients before and during chelation therapy<br />Toxicity of therapeutic drugs<br />Metametrix states that porphyrins are proteins involved in the formation of heme measured in urine. Heme is essential for the proper function of many proteins including oxygen transport, energy production, and detoxification. Proper porphyrin production is essential for our body's capacity to detoxify toxins.7<br />Porphyrins are particularly well suited for assessing heavy metal toxicity. First, the heme production pathway is a constantly-changing pathway that is active in almost every cell of the body.7 However, heme production occurs primarily in the liver, kidneys and erythroid cells.2 Any disturbance in the pathway tends to cause rapid and relatively large accumulations of intermediates, such as porphyrins.7 Second, the enzymes of the pathway are widely distributed in human tissues, and are highly sensitive to the presence of various toxins, creating the large accumulation of porphyrins in the pathway.7 Specific enzymes at various steps in the pathway are more vulnerable to interference by mercury, lead, arsenic and other toxins. Buildup of certain urinary porphyrins provides insights as to where along the pathway the interference is occurring and implicates the most likely suspects that cause this interference.<br />Metametrix claims that urinary porphyrin testing is successful in:<br />
    • Demonstrating the role of mercury in ASD (Autism Spectrum Disorder) populations
    • 2. Identifying the physiologic burden of children and adults exposed to mercury
    • 3. Tracking mercury excretion from affected children undergoing treatment
    Sources of documentation reviewed by me, however, indicate that there is a bit more to the story. It turns out that, in the first claim, while mercury has been shown to affect porphyrin levels in many with ASD, a major factor that renders ASD sufferers vulnerable to the effects of mercury lies in their inability to produce GSH (glutathione) sufficiently to avoid such effects.2 Therein, mercury’s neurotoxic effects are more expressed since GSH is the major binding agent in the processing of mercury for excretion.2 Changes in urinary porphyrin percentages due to unimpeded mercury effects may implicate diminished production capacity for GSH. Insufficient quantities of GSH may render the existing supply more susceptible to oxidation and this has been positively correlated with increasing mercury-associated urinary porphyrins.3 Additionally, a dose-response association was suggested between severity of ASD and [dys]porphyrinuria.1 <br />As for the second point, the experts agree that urinary porphyrin measurements are recommended for estimating the initial status of and tracking the effectiveness of a treatment program designed for lower the toxic burden of mercury.1, 3, 6, 2 Studies that suggest the contrary were found to be of insufficient power to substantiate their recommendations.5 However, one study did suggest that younger children seem to have inherently higher percentages of specific porphyrins in their urine than were previously known and, as such, baseline data derived from a large pool of subjects for each year of life may be of value in estimating “ideal” values for urinary porphyrins in children.6 Studies funded by entities that may have a vested interest in casting mercury in a more favorable light have acknowledged that urinary porphyrin testing is a viable indirect method of detecting subclinical levels of mercury toxicity; levels considered to be “considerably below” those associated with tissue injury in children.6 (Interestingly, this study examined changes in urinary porphyrins presumed to be caused by mercury amalgam presence in children. The average number of mercury amalgams per child was near 17!) While mercury levels capable of injuring tissue are a threat to be taken seriously, the sub-clinical implications and long term sequelae of impaired heme synthesis due to heavy metal interference seem worth investigating, too.<br />The third point given by Metametrix makes utilitarian sense as urinary porphyrin testing is not an invasive test and has been shown to correlate nicely with chelation therapy.1<br />An examination of the marketing materials available via Metametrix reveals several resources. A patient brief provided on the website provides the clinician with a valuable handout that explains clearly why a patient may qualify to have this test done.<br />http://www.metametrix.com/files/test-menu/patient-briefs/Porphyrins-PB.pdf<br />PDF accessible instructions for the appropriate handling and processing of the specimen are also provided to the clinician on the website, thus eliminating the guess work and minimizing confusion. Sample reports and interpretive guides are also given, there.<br />http://www.metametrix.com/files/test-menu/kit-instructions/Porphyrins-KI.pdf<br />http://www.metametrix.com/files/test-menu/sample-reports/Porphyrins-SR.pdf<br />http://www.metametrix.com/files/test-menu/interpretive-guides/Porphyrins-IG.pdf<br />The ease of use and utility of having these documents available and only a “mouse click” away is, in itself, a tremendous marketing tool for this test since other potentially effective analysis companies might not be utilized as much if the ease of accessing their applicable support materials is compromised in some way. Additionally, articles, books and podcasts are made available on the website which affords<br />http://www.metametrix.com/test-menu/profiles/toxicants-and-detoxification/porphyrins-profile?t=resources<br />the researcher further information before delving into the literature on their own to make a more informed decision; an endeavor worth doing since none of their references listed are later than 2007.<br />http://www.metametrix.com/learning-center/references/porphyrins<br />Despite the lack of updates to their collection of credible research articles, the information has proven to be consistent in supporting their claims since 2007.<br />Another great perk to the website is the addition of CPT codes. As clinicians, the subject of reimbursement always comes up. As a consequence, having the applicable codes readily available for billing is a nice convenience. The coverage for this test is, of course, subject to the whims of the 3rd party payer’s determination of medical necessity. Also, as a New York State practitioner, this test is not within my scope of practice and I was not provided with the out-of-pocket expense to have the test run. Instead, I have the option of running the following with their corresponding pre-paid costs:<br /> TestSpecimenCost0155 Toxic Metals - 6-8 hours Urine95.000159 Toxic Metals - 24 hours Urine95.00<br />This is off the main point of this discussion but is worth mentioning, nevertheless.<br />Ultimately, the Porphyrins Profile seems to be a worthwhile means of gleaning the initial status of mercury effects and the effects of its treatment, albeit indirectly. This test should be included for the assessment of autistic persons or for those patients whom clinical insights point to metal toxicity, mercury, in particular. Because mercury’s roll in changing the porphyrin ratios was such a focus in the literature obtained, speaking to the utility of this test for assessing the effects of other metals or xenobiotics on these ratios is outside the limit of what I researched. Finally,depending on the state that one practices in, the Porphyrin Profile may or may not be available for use in accordance with the scope of practice. <br />References:<br />1. Geier DA, Geier MR. (2006). A prospective assessment of porphyrins in autistic disorders: a potential <br />marker for heavy metal exposure. Neurotoxicity Research. Aug;10(1):57-64.<br />2. Geier DA, Geier MR. (2007). A prospective study of mercury toxicity biomarkers in autistic spectrum <br />disorders. Journal of Toxicology and Environmental Health. Part A. Oct;70(20):1723-30.<br />3. Geier DA, Kern JK, Garver CR, Adams JB, Audhya T, Nataf R, Geier MR. (2009) Biomarkers of <br />environmental toxicity and susceptibility in autism. Journal of the Neurological Sciences. May <br />15;280(1-2):101-8.<br />4. Ratajczak HV.(2011). Theoretical aspects of autism: biomarkers--a review. Journal of Immuno-<br />toxicology. Jan-Mar;8(1):80-94.<br />5. Woods JS, Armel SE, Fulton DI, Allen J, Wessels K, Simmonds PL, Granpeesheh D, Mumper E, <br />Bradstreet JJ, Echeverria D, Heyer NJ, Rooney JP. (2010). Urinary porphyrin excretion in <br />neurotypical and autistic children. Environ Health Perspect. Oct;118(10):1450-7.<br />6. Woods JS, Martin MD, Leroux BG, DeRouen TA, Bernardo MF, Luis HS, Leitão JG, Simmonds PL, <br />Echeverria D, Rue TC. (2009). Urinary porphyrin excretion in children with mercury amalgam <br />treatment: findings from the Casa Pia Children's Dental Amalgam Trial. Journal of Toxicology and Environmental Health. Part A. 72(14):891-6.<br />7. http://www.metametrix.com/test-menu/profiles/toxicants-and-detoxification/porphyrins-profile<br />