Investigation of raised ALP

Physiological causes

  • Normal variation – statistically, 2.5% of the population will have levels above the ULN.
  • Analytical variation – combined analytical & biochemical variation is approx 8%. Levels increase by approx 6% if sample stored for 96 hrs at room temp before analysis.
  • Familial (intestinal ALP)
  • Pregnancy
  • Adolescent growth spurt
  • Drugs (see below)
  • Postprandial rise after fatty meals (occurs in people with Types B & O)

In one study, 95% of raised alkaline phosphatases proved to be of no significance.

Common drugs causing ALP rises

May act via enzyme induction or hepatic cholestasis.

  • Antibiotics: penicillins, erythromycin, aminoglycosides
  • Antiepileptics: carbamazepine, phenobarbital, phenytoin
  • Cetirizine
  • Antihypertensives: captopril, diltiazem, felodipine
  • DMARDs: penicillamine, sulfas
  • COC
  • Steroids
  • Psychotropics: MAOIs, chlorpromazine

Pathological causes other than liver or bone

  • CCF
  • ESRF
  • Hyperthyroidism
  • Acute phase reactant in extrahepatic infection
  • Intestinal disease


History: Abdominal pain/swelling, bone pain, appetite/weight loss, clinical features of hepatic failure/ESRF/CCF.

Bloods: Repeat within 4 weeks, together with calcium profile, gamma-GT, U&Es, FBC, & TSH.

Any other abnormalities – follow up as appropriate.

Raised ALP + GGT – ALP assumed to be of hepatic origin. If ALP <1.5 x ULN repeat in 3/12. If >1.5 x ULN, or persistently raised, then proceed to:

  • Liver USS (for cholestasis or infiltrative lesion)
  • Antimitochondrial antibodies (primary biliary cirrhosis)

If tests negative and ALP persistently > 1.5 x ULN, refer to hepatologist. If tests negative and ALP < 1.5 x ULN, evaluate for symptoms in 6/12 – liver biopsy tends not to be very helpful, further Ix not cost-effective.

Raised ALP with normal GGT/other tests – ALP non-hepatic, probably bony origin. Causes include:

  • Vitamin D deficiency
  • Paget’s disease of bone
  • Adolescent growth spurts
  • Healing fractures
  • Bone tumours (these and fractures should be clinically evident)

If asymptomatic, check Vitamin D levels and treat any deficiency. If Vitamin D normal and ALP <1.5 x ULN, investigate only if symptoms develop. If ALP >1.5 x ULN, possibly worth doing bone scintigraphy to identify early asymptomatic Paget’s disease (opinion divided on whether worthwhile to treat this prior to symptoms developing).

Moderately impressive flowchart


About Dr Sarah

I'm a GP with a husband and two young children.
This entry was posted in BMJ, Clinical biochemistry, Credits 2013, Gastroenterology, Liver, Liver. Bookmark the permalink.

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