A 40-year-old female presented to the physician for evaluation of worsening fatigue. She has no other medical problems. She does not use tobacco, alcohol or drugs. Vital signs are within normal limits. Physical examination is within normal limits. Laboratory evaluation shows an alkaline phosphatase level of 180 U/L. Which of the following should be checked next?

Question

A 40-year-old female presented to the physician for evaluation of worsening fatigue.  She has no other medical problems.  She does not use tobacco, alcohol or drugs.  Vital signs are within normal limits.  Physical examination is within normal limits.  Laboratory evaluation shows an alkaline phosphatase level of 180 U/L.  Which of the following should be checked next?

Quizplus · Accepted Answer

Broadly speaking, laboratory tests used in the evaluation of hepatobiliary disease either assess liver functionality (eg, prothrombin time, bilirubin, albumin, cholesterol) or the structural integrity and cellular intactness of the liver (eg, transaminases) or the biliary tract (eg, alkaline phosphatase, γ-glutamyl transferase). Alkaline phosphatase represents a group of enzymes associated with metabolic activity in a number of tissues, including liver, bone, intestine, kidney, placenta, leukocytes, and some neoplasms. Bone and liver are the primary sources of alkaline phosphatase, with threefold elevations considered a relatively nonspecific finding for many liver diseases. To clarify the importance of a moderately elevated alkaline phosphatase, the hepatic γ-glutamyl transpeptidase (GGTP) should be evaluated. γ-glutamyl transpeptidase is an enzyme predominantly present in hepatocytes and biliary epithelia. While it too can be found in various extrahepatic tissues (organs such as kidney, spleen, pancreas, heart, lung, and brain), GGTP is not present to a significant extent in bone. It is therefore particularly useful in determining whether an elevated alkaline phosphatase is of hepatic or bony origin. (Choice A) Measurement of unconjugated bilirubin (especially in contrast to conjugated bilirubin) can be of assistance in distinguishing hemolytic conditions from hepatic dysfunction or bile duct obstruction. This test is not particularly helpful in following up an elevated alkaline phosphatase. (Choice B) Lactate dehydrogenase is a relatively nonspecific test that can be of some assistance in the evaluation of tissue injury or death. It is not the most helpful test in following up an elevated alkaline phosphatase. (Choice C) Serum ammonia levels can be of assistance in determining the extent of liver failure or gastrointestinal bleeding, among other conditions. It is not the most helpful test in following up an elevated alkaline phosphatase. (Choice D) Prothrombin time is of assistance in assessing coagulative ability and liver functionality, especially in the acute setting. It is not the most helpful test in following up an elevated alkaline phosphatase. (Choice F) Aspartate aminotransferase is of assistance in assessing and monitoring hepatic damage. It is not the most helpful test in following up an elevated alkaline phosphatase. Educational Objective: A moderately elevated alkaline phosphatase of unclear etiology should be followed up with γ-glutamyl transpeptidase.

A 40-Year-Old Female Presented to the Physician for Evaluation of Worsening