MCAS Blood Tests and Urine Labs: Which to Ask Your Doctor For

The lab tests Dr. Hoffman recommends for diagnosing mast cell activation syndrome, with specimen handling and medication rules, and why negative results are common even when the history fits.

A calm woman shows the doctor a phone full of photos of her flushed, hive-covered skin while a face-down lab report and a cooler of melted ice sit forgotten on the desk.
In one paragraph: the five tests Dr. Hoffman considers most important are plasma histamine, 24-hour urine N-methylhistamine, plasma and 24-hour urine prostaglandin D2, and chromogranin A, most of which must be chilled. Results fluctuate as symptoms wax and wane and specimens are often mishandled, so positive lab work is obtained only 20% of the time. Tests may need repeating during flare-ups, and false negatives can occur despite a history highly consistent with MCAS.

Which lab tests to ask your doctor for to diagnose MCAS

MCAS can be difficult to diagnose because lab test results may fluctuate as symptoms wax and wane. Many tests may need to be repeated during times of symptom flare-ups. Poor handling of specimens by the laboratory is also a real issue affecting results. Lab testing may thus result in false negatives despite a clinical history highly consistent with MCAS. Furthermore, MCAS doesn’t always cause abnormalities in lab work, adding to the complexity of diagnosis. Positive lab work is obtained only 20% of the time.

If you’re interested in getting lab work done to check for MCAS, I recommend the tests listed below. The top five, in bold, are the most important and necessary to establish a diagnosis:

  1. Histamine – plasma – Quest 36586 – must be chilled. Normal range – 28-51 ug/l.
  2. N-Methylhistamine – 24-hour urine – must be chilled. Normal range – less than 200 mcg/g.
  3. Prostaglandin D2 – plasma – must be chilled. Must be off NSAIDS (Motrin, Advil), aspirin, ASA, anything containing aspirin, for 5 days.
  4. Prostaglandin D2 (PGD2) – 24-hour urine – chilled. Must be off NSAIDS (Motrin, Advil), aspirin, ASA, anything containing aspirin, for 5 days.
  5. Chromogranin A – Quest 16379 – must be off proton pump inhibitors (PPIs) and H2 blockers (Pepcid and Zantac) for 5 days before tests, since they can falsely elevate chromogranin A.
  6. Prostaglandin 11-beta F2 Alpha (PGF2alpha) – 24-hour urine – chilled. Must be off NSAIDS (Motrin, Advil), aspirin, ASA, anything containing aspirin, for 5 days.
  7. Serum Tryptase – Quest 34484. Rarely elevated in MCAS. NR less than 11.5 ng/ml. Positive if increase over baseline of 20% or baseline greater than 15.
  8. Leukotriene E4 – 24-hour urine – chilled. Must be off NSAIDS (Motrin, Advil), aspirin, ASA, anything containing aspirin, for 5 days.
  9. Plasma heparin Anti-XA (must be off heparin products) – chilled. Degrades quickly.
  10. Blood clotting profile – Thrombin/PT/PTT/INR.
  11. Anti-IgE Receptor antibody.
  12. Neuron Specific Enolase – Quest 34476.
  13. Plasma pheochromocytoma workup.
  14. Porphyria workup.
  15. Factor VIII deficiency.
  16. Plasma free norepinephrine – Quest 37562.
  17. Urinary metanephrines – can b done in normal Calgary labs.
  18. Immunoglobulins – IgG, IgM, IgE, IgA
  19. Bone marrow biopsy looking for the following markers: CD117/CD25; CD117/CD2.
  20. Gastrin
  21. Ferritin
  22. CBC – eosinophils, basophils.
  23. Antiphospholipid antibodies.
  24. Genetic testing looking for Phase 1 and Phase II liver detox and methylation defects.
  25. Dunwoody Labs – test zonulin, histamine, DAO enzyme deficiency.

Many of these tests require specimens that are chilled by using a special centrifuge as the mast cell mediators are fleeting and degrade very quickly if not handled properly.

Further tests that may be of help:

  1. MTHFR gene mutations
  2. MAT gene mutations
  3. DAO gene mutations
  4. HNMT gene mutations. The liver plays a role in histamine intolerance. Histamine is not just disassembled in the gut by diamine oxidase (DAO). It is also disassembled in the liver, where it is in high concentrations, by HNMT.
  5. Glutathione levels. If glutathione levels are depleted, the inflammatory mediators released by mast cells may not be adequately neutralized by glutathione, the master antioxidant. This can lead to a vicious circle where oxidative stress results in mast-cells releasing inflammatory chemicals, which need to be detoxified by Phase 1 of the liver. If glutathione is low, the liver will be unable to neutralize them, resulting in further inflammation and oxidative stress.

These tests can help you identify whether MCAS is the cause of your mysterious and seemingly unrelated symptoms.

Frequently asked questions

What lab tests are used to diagnose MCAS?
Dr. Hoffman lists plasma histamine, 24-hour urine N-methylhistamine, plasma and 24-hour urine prostaglandin D2, and chromogranin A as the most important tests for establishing a diagnosis. Further tests include PGF2alpha, serum tryptase, leukotriene E4, plasma heparin Anti-XA, immunoglobulins, a CBC for eosinophils and basophils, and others.
Why are MCAS lab tests often negative?
Results fluctuate as symptoms wax and wane, and poor specimen handling by laboratories affects results. MCAS also does not always cause abnormalities in lab work, and positive lab work is obtained only 20% of the time.
Why do MCAS test samples need to be chilled?
Mast cell mediators are fleeting and degrade very quickly if not handled properly. Many of the tests therefore require specimens chilled using a special centrifuge.
Which medications affect MCAS test results?
NSAIDs such as Motrin and Advil, aspirin and anything containing aspirin are stopped for 5 days before prostaglandin and leukotriene E4 tests. Proton pump inhibitors and H2 blockers such as Pepcid and Zantac can falsely elevate chromogranin A and are stopped for 5 days before that test.
Is tryptase elevated in MCAS?
Serum tryptase is rarely elevated in MCAS. The normal range given is less than 11.5 ng/ml, and it is considered positive with an increase of 20% over baseline or a baseline greater than 15.