investigation of asymptomatic raised alkaline phosphatase

Last edited 09/2019 and last reviewed 10/2023

Baseline investigations for a raised alkaline phosphatase include (1,2):

  • bone profile
    • may include bone isoenzyme of alkaline phosphatase - not widely available
  • LFTs
  • GGT - a marker of cholestasis and biliary disease
    • GGT is abundant in the liver and also present in the kidney, intestine, prostate and pancreas but not in bone - thus can be useful in confirming that an elevated alkaline phosphatase is of liver and not bony origin
  • vitamin D - vitamin D deficiency can be the cause an asymptomatic raised alkaline phosphatase
  • U+Es - renal osteodystrophy can cause a raised alkaline phosphatase
  • TFTs - may be associated with elevation of alanine aminotransferase and alkaline phosphatase, which is mainly of bone origin, in hyperthyroidism (3)
  • FBC, ESR, CRP - raised inflammatory markers would be suggestive of causes such as undiagnosed malignancy or metastatic disease

If a raised alkaline phosphatase level is determined to be of liver origin then first line investigations in a patient include (1):

  • liver ultrasonography, any dilatation should be investigate by ERCP
  • serum antimitochondrial antibodies - to identify possible PBC

If serologic test for antimitochondrial levels is negative and ultrasound is normal but the alkaline phosphatase remains increased more than 50% above the normal level then other investigations such as liver biopsy and either magnetic resonance cholangiopancreatography or endoscopic retrograde cholangiopancreatography are suggested (1). However if the increase in alkaline phosphatase is less than 50% and the patient has no symptoms and the results of all liver-enzymes are normal, then observation alone has been suggested as the appropriate management (1).

Notes:

  • determination whether the elevated alkaline phosphatase is of liver or bone origin:
    • electrophoresis to determine origin of alkaline phosphatase - not widely available
    • measurement of GGT (gamma glutamyltransferase) or 5'- nucleotidase - levels of these enzymes are generally raised in parallel with the elevation in alkaline phosphatase in patients with liver disorders, but they are not increased in patients with bone disorders

  • Sometimes it is useful to look at the relationship of ALP to bilirubin and lactate dehydrogenase (LD) levels (4)

    Pathology Alkaline Phosphatase Bilirubin LD
    Intra or extrahepatic cholestasis Increased Increased Normal
    Focal benign cholestasis Increased Normal Normal
    Focal malignant cholestasis Increased Normal Increased

  • If alkaline phosphatase is raised in an asymptomatic patient and serum bilirubin, liver transaminases, creatinine, adjusted calcium, thyroid function, and blood count are normal (5):
    • consider growth spurts in adolescents, pregnancy in women, drugs, and age related increases
    • as most likely sources are either bone or liver, differentiate by measuring GGT (raised in liver) and investigate accordingly
    • for liver cases investigate with abdominal ultrasound scan (cholestasis and hepatic space occupying lesion) and antimitochondrial antibodies (primary biliary cirrhosis)
    • for bone cases investigate vitamin D

Reference:

Related pages:

antimitochondrial autoantibodies

suggested protocol for investigation and referral of an isolated asymptomatic raised alkaline phosphatase in an adult in primary care