Which of the following substances, sometimes used as a tumor marker, is increased two- or threefold in a normal pregnancy?

Alkaline phosphatase (ALP) is an enzyme that is commonly associated with the liver, bones, and placenta. During a normal pregnancy, particularly in the second and third trimesters, ALP levels can increase significantly, often two- to threefold. This rise is primarily due to the placental production of the enzyme, which is a normal physiological response to pregnancy.

Elevated ALP in pregnant individuals is typically not a cause for concern; rather, it is an expected finding and can sometimes be used as a tumor marker, particularly in distinguishing between conditions affecting bone and liver. The increase can sometimes be confused with pathologies affecting these systems; however, the context of pregnancy signifies that this elevation is usually benign and physiological.

The other substances listed do not exhibit the same pattern of elevation during a normal pregnancy. Calcitonin, adrenocorticotropic hormone (ACTH), and neuron-specific enolase do not typically show significant increases solely due to pregnancy, and thus are not relevant to this specific context of increased levels associated with normal gestational changes.