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Epic Code LAB398 Heavy Metals Screen, with Reflex, 24 Hour, Urine

Important Note

Patient Preparation:

1. High concentrations of gadolinium and iodine are known to interfere with most metals tests. If either gadolinium- or iodine-containing contrast media has been administered, a specimen should not be collected for 96 hours.

2. Patient should not eat seafood for a 48-hour period prior to start of, or during, collection.

Reporting Name

Heavy Metal Scrn w/Reflex, 24 Hr, U

Performing Laboratory

Mayo Clinic Laboratories in Rochester

Clinical Information

Arsenic:

Arsenic is a naturally occurring element that is usually found in the environment combined with other elements such as oxygen, chlorine, and sulfur. Arsenic combined with these elements is called inorganic arsenic. Arsenic combined with carbon and hydrogen is referred to as organic arsenic. The organic forms (eg, arsenobetaine and arsenocholine) are relatively nontoxic, while the inorganic forms are toxic. The toxic inorganic forms are arsenite (As[3+]/As[III]) and arsenate (As[5+]/As[V]). Inorganic As(V) is readily reduced to inorganic As(III) which is then primarily broken down to less toxic methylated metabolites monomethylarsinic acid (MMA) and subsequently dimethylarsinic acid (DMA).

 

People are exposed to arsenic by eating food, drinking water, or breathing air. Of these, food is usually the largest source of arsenic. The predominant dietary source of arsenic is seafood, followed by rice/rice cereal, mushrooms, and poultry. While seafood contains the greatest amounts of arsenic, for fish and shellfish, this is mostly in an organic form of arsenic called arsenobetaine, which is much less harmful. Some seaweed may contain arsenic in the inorganic form, which is more toxic. In the United States, some areas also contain high natural levels of arsenic in rock, which can lead to elevated levels in the soil and drinking water. Occupational (eg, copper or lead smelting, wood treating, or pesticide application) exposure is another source where people may be introduced to elevated levels of arsenic. Lastly, hazardous waste sites may contain large quantities of arsenic and if not disposed of properly may get into the surrounding water, air, or soil.

 

A wide range of signs and symptoms may be seen in acute arsenic poisoning including headache, nausea, vomiting, diarrhea, abdominal pain, hypotension, fever, hemolysis, seizures, and mental status changes. Symptoms of chronic poisoning, also called arseniasis, are mostly insidious and nonspecific. The gastrointestinal tract, skin, and central nervous system are usually involved. Nausea, epigastric pain, colic abdominal pain, diarrhea, and paresthesias of the hands and feet can also occur.

 

Since arsenic is excreted predominantly by glomerular filtration, measurement of arsenic in urine is the most reliable means of detecting arsenic exposures within the last several days.

 

Cadmium:

The toxicity of cadmium resembles the other heavy metals (arsenic, mercury, and lead) in that it attacks the kidney; renal dysfunction with proteinuria with slow onset (over a period of years) is the typical presentation. Measurable changes in proximal tubule function, such as decreased clearance of para-aminohippuric acid also occur over a period of years, and precede overt renal failure.

 

Breathing the fumes of cadmium vapors leads to nasal epithelial deterioration and pulmonary congestion resembling chronic emphysema.

 

For nonsmokers, the primary source of cadmium exposure is from the food supply. In general, leafy vegetables such as lettuce and spinach, potatoes and grains, peanuts, soybeans, and sunflower seeds contain high levels of cadmium. For smokers, the most common source of cadmium exposure is tobacco smoke, which has been implicated as the primary sources of the metal leading to reproductive toxicity in both males and females.

 

The concentration of cadmium in the kidneys and in the urine is elevated in some patients exposed to cadmium.

 

Mercury:

The correlation between the levels of mercury (Hg) excretion in the urine and the clinical symptoms is considered poor.

 

It had always been thought that urine was a more appropriate marker of inorganic mercury, because organic mercury represented only a small fraction of urinary mercury. Based on possible demethylation of methylmercury within the body, urine may represent a mixture of dietary methylmercury and inorganic mercury. Seafood consumption can contribute to urinary mercury levels (up to 30%),(1) which is consistent with the suggestion that due to demethylation processes in the human body, a certain proportion of urinary mercury can originate from dietary consumption of fish/seafood.(2)

 

For additional information, see HG / Mercury, Blood

 

Lead:

Increased urine lead excretion rate indicates significant lead exposure. Measurement of urine lead excretion rate before AND after chelation therapy has been used as an indicator of lead exposure. However, the American College of Medical Toxicology (ACMT 2010) position statement on post-chelator challenge urinary metal testing states that "post-challenge urinary metal testing has not been scientifically validated, has no demonstrated benefit, and may be harmful when applied in the assessment and treatment of patients in whom there is concern for metal poisoning."

 

Blood lead is the best clinical correlation of toxicity.

 

For additional information, see PBDV / Lead, Venous, with Demographics, Blood.

Useful For

Detecting arsenic, cadmium, mercury, and lead exposure and toxicity using 24-hour urine specimen

Specimen Type

Urine


Specimen Required


Patient Preparation:

1. High concentrations of gadolinium and iodine are known to interfere with most metals tests. If either gadolinium- or iodine-containing contrast media has been administered, a specimen should not be collected for 96 hours.

2. Patient should not eat seafood for a 48-hour period prior to start of, or during, collection.

Supplies: Urine Tubes, 10 mL (T068)

Collection Container/Tube: Clean, plastic aliquot container with no metal cap or glued insert

Submission Container/Tube: Plastic, 10-mL urine tube

Specimen Volume: 10 mL

Collection Instructions:

1. Collect urine for 24 hours.

2. Refrigerate specimen within 4 hours of completion of 24-hour collection.

3. See Trace Metals Analysis Specimen Collection and Transport in Special Instructions for complete instructions.

Additional Information: See Urine Preservatives-Collection and Transportation for 24-Hour Urine Specimens in Special Instructions for multiple collections.


Laboratory Test Directory Note:

24H/NP/R+PO/R

Specimen Minimum Volume

3 mL

Laboratory Test Directory Note:

SPECTRUM HEALTH LABORATORY MINIMUM VOLUME 10 mL

Specimen Stability Information

Specimen Type Temperature Time Special Container
Urine Refrigerated (preferred) 7 days
  Frozen  7 days

Reject Due To

All specimens will be evaluated at Mayo Clinic Laboratories for test suitability.

Day(s) Performed

Monday through Friday

Reference Values

ARSENIC:

0-17 years: not established

≥18 years: <35 mcg/24 hour

 

CADMIUM:

0-17 years: not established

≥18 years: <0.7mcg/24 hour

 

MERCURY:

0-17 years: not established

≥18 years: <2 mcg/24 hour

Toxic concentration: >50 mcg/24 hour

 

The concentration at which toxicity is expressed is widely variable between patients.

50 mcg/24 hour is the lowest concentration at which toxicity is usually apparent.

 

LEAD:

0-17 years: not established

≥18 years: <2 mcg/24 hour

Interpretation

Arsenic:

Mayo Clinic uses the American Conference of Governmental Industrial Hygienists (ACGIH) biological exposure index (BEI) as the reference value. The BEI is the sum of all the toxic species (inorganic arsenic plus methylated arsenic metabolites).

 

Physiologically, arsenic exists in a number of toxic and nontoxic forms. The total arsenic concentration reflects all the arsenic present in the sample regardless of species (e.g. inorganic vs. methylated vs. organic arsenic). The measurement of urinary total arsenic levels is generally accepted as the most reliable indicator of recent arsenic exposure. However, if the total urine arsenic concentration is elevated, arsenic speciation must be performed to identify if it is the toxic forms (e.g. inorganic and methylated arsenic forms) or the relatively non-toxic organic forms (e.g. arsenobetaine and arsenocholine).

 

The inorganic toxic forms of arsenic (e.g. As[III] and As[V]) are found in the urine shortly after ingestion, whereas the less toxic methylated forms, monomethylarsinic acid (MMA) and dimethylarsinic acid (DMA), are the species that predominate longer than 24 hours after ingestion. In general, urinary As(III) and As(V) concentrations peak in the urine at approximately 10 hours and return to normal 20 to 30 hours after ingestion. Urinary MMA and DMA concentrations normally peak at approximately 40 to 60 hours and return to baseline 6 to 20 days after ingestion.

 

After a seafood meal (seafood generally contains the nontoxic, organic form of arsenic (eg, arsenobetaine), the urine output of arsenic may increase to over 300 mcg/specimen for a day, after which it will decline.

 

This test can determine if the patient has been exposed to above-average levels of arsenic. It cannot predict whether the arsenic levels in their body will affect their health.

 

Cadmium:

In chronic cadmium exposure, the kidneys are the primary target organ. Urine concentrations of cadmium can be useful to assess long-term exposure and determine cadmium body burden. Collection of urine over 24 hours minimizes fluctuations of observed cadmium concentrations in random urine samples.

 

Cadmium excretion above 3.0 mcg/g creatinine indicates significant exposure to cadmium. For occupational testing, the Occupational Safety and Health Administration (OSHA) cadmium standard is <3.0 mcg/g creatine and the BEI is 5 mcg/g creatinine.

 

Mercury:

Daily urine excretion of mercury above 50 mcg/day indicates significant exposure (per World Health Organization standard).

 

Lead:

Measurements of urinary lead (Pb) levels have been used to assess lead exposure. However, like lead blood, urinary lead excretion mainly reflects recent exposure and thus shares many of the same limitations for assessing Pb body burden or long-term exposure.(3,4)

 

Urinary lead concentration increases exponentially with blood lead and can exhibit relatively high intra-individual variability, even at similar blood lead concentrations.(5,6)

Cautions

Consumption of seafood before collection of a urine specimen for arsenic testing is likely to result in a report of an elevated concentration of arsenic found in the urine, which can be clinically misleading.

 

Collection of urine specimens through a catheter frequently results in elevated values because rubber contains trace amounts of cadmium that are extracted as urine passes through the catheter.

 

To avoid contamination by dust, specimen should be collected away from the site of suspected exposure.

Clinical Reference

1. Snoj Tratniid J, Falnoga I, Mazej D, et al: Results of the first national human biomonitoring in Slovenia: Trace elements in men and lactating women, predictors of exposure and reference values. Int J Hyg Environ Health. 2019;222(3):563-582

2. Sherman LS, Blum JD, Franzblau A, Basu N: New insights into biomarkers of human mercury exposure using naturally occurring mercury stable isotopes. Envrn Sci Technol. 2013;47(7):3403-3409

3. Sakai T: Biomarkers of lead exposure. Ind Health. 2000;38(2):127-142

4. Skerfving S:Biological monitoring of exposure to inorganic lead. In: Clarkson TW, Friberg L, Nordberg GF, Sager PR, eds. Biological Monitoring of Toxic Metals. Rochester Series on Environmental Toxicity. Springer; 1988:169-197

5. Gulson BL, Jameson CW, Mahaffey KR, et al: Relationships of lead in breast milk to lead in blood, urine, and diet of the infant and mother. Environ Health Perspect. 1998;106(10):667-67

6. Skerfving S, Ahlgren L, Christoffersson JO: Metabolism of inorganic lead in man. Nutr Res 1985;Suppl 1:601-607

7. Fillol CC, Dor F, Labat L, et al: Urinary arsenic concentrations and speciation in residents living in an area with naturally contaminated soils. Sci Total Environ. 2010 Feb 1;408(5):1190-1191

8. Caldwell KL, Jones RL, Verdon CP, Jarrett JM, Caudill SP, Osterloh JD: Levels of urinary total and speciated arsenic in the US population: National Health and Nutrition Examination Survey 2003-2004. J Expo Sci Environ Epidemiol. 2009 Jan;19(1):59-68

9. Lee R, Middleton D, Caldwell K, et al. A review of events that expose children to elemental mercury in the United States. Environ Health Perspect. 2009 Jun;117(6):871-878

10. Kosnett MJ, Wedeen RP, Rotherberg SJ, et al: Recommendations for medical management of adult lead exposure. Environ Health Perspect. 2007;115:463-471

11. De Burbane C, Buchet JP, Leroyer A, et al: Renal and neurologic effects of cadmium, lead, mercury, and arsenic in children: evidence of early effects and multiple interactions at environmental exposure levels. Environ Health Perspect. 2006;114:584-590

12. Agency for Toxic Substances and Disease Registry: Toxicological profile for arsenic. US Department of Health and Human Services. 2007. https://www.atsdr.cdc.gov/ToxProfiles/tp2.pdf

13. Strathmann FG, Blum LM: Toxic elements. In: Rifai N, Horwath AR., Wittwer CT, eds. Tietz Textbook of Clinical Chemistry and Molecular Diagnostics. 6th ed. Elsevier; 2018:chap 42

14. Keil DE, Berger-Ritchie J, McMillin GA: Testing for toxic elements: a focus on arsenic, cadmium, lead, and mercury. Lab Med, 2011 Dec:42(12):735–742. https://academic.oup.com/labmed/article/42/12/735/2504927

15. Navas-Acien A, Francesconi KA, Silbergeld EK, Guallar E. Seafood intake and urine concentrations of total arsenic, dimethylarsinate and arsenobetaine in the US population. Environ Res. 2011 Jan;111(1):110-118. doi: 10.1016/j.envres.2010.10.009

16. Tchounwou PB, Yedjou CG, Udensi UK, et al: State of the science review of the health effects of inorganic arsenic: Perspectives for future research. Environ Toxicol. 2019 Feb;34(2):188-202. doi: 10.1002/tox.22673

Method Name

Inductively Coupled Plasma-Mass Spectrometry (ICP-MS)

Method Description

Arsenic (As), cadmium (Cd), mercury (Hg), and lead (Pb) in urine are analyzed by inductively coupled plasma-mass spectrometry (ICP-MS) in kinetic energy discrimination (KED) mode using gallium (Ga), rhodium (Rh), and iridium (Ir) as internal standards and a 5% nitric acid salt matrix calibration.(Unpublished Mayo method)

Report Available

1 to 3 days

Test Classification

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

82175

82300

83825

83655

LOINC Code Information

Test ID Test Order Name Order LOINC Value
HMU24 Heavy Metal Scrn w/Reflex, 24 Hr, U 94575-8

 

Result ID Test Result Name Result LOINC Value
8678 Cadmium, 24 Hr, U 5612-7
48539 Arsenic, 24 Hr, U 5587-1
92408 Mercury, 24 Hr, U 6693-6
92409 Lead, 24 Hr, U 5677-0
TIME4 Collection Duration 13362-9
92215 Total Arsenic Concentration 21074-0
VL16 Total Volume 3167-4

Profile Information

Test ID Reporting Name Available Separately Always Performed
ASHU Arsenic, 24 Hr, U Yes, (order ASU24) Yes
CDHMU Cadmium, 24 Hr, U Yes, (order CDU) Yes
HGHU Mercury, 24 Hr, U Yes, (order HGU) Yes
PBHU Lead, 24 Hr, U Yes, (order PBU) Yes

Reflex Tests

Test ID Reporting Name Available Separately Always Performed
SPASU Arsenic Speciation, 24 Hr, U Yes No

Urine Preservative Collection Options

Note: The addition of preservative or application of temperature controls must occur within 4 hours of completion of the collection.

Ambient

No

Refrigerate

Preferred

Frozen

OK

50% Acetic Acid

OK

Boric Acid

No

Diazolidinyl Urea

No

6M Hydrochloric Acid

OK

6M Nitric Acid

No

Sodium Carbonate

No

Thymol

No

Toluene

No