Test Catalog

Test ID: MET    
Methemoglobin and Sulfhemoglobin, Blood

Useful For Suggests clinical disorders or settings where the test may be helpful

Diagnosing methemoglobinemia and sulfhemoglobinemia


Identifying cyanosis due to other causes, such as congenital heart disease

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test


When iron in hemoglobin is oxidized from the normal divalent state to a trivalent state, the resulting brownish pigment is methemoglobin. Methemoglobin cannot combine reversibly with oxygen and is associated with cyanosis.


Methemoglobinemia, with or without sulfhemoglobinemia, is most commonly encountered as a result of administration of medications such as phenacetin, phenazopyridine, sulfonamides, local anesthetics, dapsone, or following ingestion of nitrites or nitrates. Congenital methemoglobinemias are rare. They are either due to:

-Deficiency of methemoglobin reductase (also called cytochrome B5 reductase or diaphorase) in erythrocytes, an autosomal recessive disorder.

-One of several intrinsic structural disorders of hemoglobin, called methemoglobin-M, all of which are inherited in the autosomal dominant mode.


Methemoglobinemia responds to treatment with methylene blue or ascorbic acid.



Sulfhemoglobin cannot combine with oxygen. Sulfhemoglobinemia is associated with cyanosis and often accompanies drug-induced methemoglobinemia. Sulfhemoglobinemia can be due to exposure to trinitrotoluene or zinc ethylene bisdithiocarbamate (a fungicide), or by ingestion of therapeutic doses of flutamide.


In contrast to methemoglobinemia, sulfhemoglobinemia persists until the erythrocytes containing it are destroyed. Therefore, blood level of sulfhemoglobin declines gradually over a period of weeks.


Patients with sulfhemoglobinemia often also have methemoglobinemia. There is no specific treatment for sulfhemoglobinemia. Therapy is directed at reversing the methemoglobinemia, if present.

Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.


0-11 months: not established

> or =1 year: 0.0-1.5% of total hemoglobin



0-11 months: not established

> or =1 year: 0.0-0.4% of total hemoglobin

Interpretation Provides information to assist in interpretation of the test results

In congenital methemoglobinemia, the methemoglobinemia concentration in blood is about 15% to 20% of total hemoglobin. Such patients are mildly cyanotic and asymptomatic.


In acquired (toxic) methemoglobinemia, the concentration may be much higher. Symptoms may be severe when methemoglobin is >40% of hemoglobin. Very high concentrations (>70%) may be fatal.

Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

Methemoglobin is unstable and is reduced to hemoglobin at a rate of about 40% per day at 0 to 4 degrees C.


A normal methemoglobin value obtained with stored or shipped specimens does not exclude prior mild methemoglobinemia. However, significant methemoglobinemia will still be demonstrable.


Sulfhemoglobin is stable and does not change in stored or shipped specimens.

Clinical Reference Recommendations for in-depth reading of a clinical nature

Beutler E: Methemoglobinemia and other causes of cyanosis. In Hematology. Sixth edition. Edited by WJ Williams, E Beutler, AJ Erslev, MA Lichtman. New York, McGraw-Hill Book Company, 2001, pp 611-614