Practice Rational Testing

Interpreting an isolated raised serum alkaline phosphatase level in an asymptomatic patient

BMJ 2013; 346 doi: http://dx.doi.org/10.1136/bmj.f976 (Published 03 April 2013) Cite this as: BMJ 2013;346:f976
  1. Kate Elizabeth Shipman, specialist trainee year 4, metabolic medicine,
  2. Ashley David Holt, foundation year 2 doctor,
  3. Rousseau Gama, consultant chemical pathologist
  1. 1New Cross Hospital, Clinical Chemistry, Wolverhampton WV10 0QP, UK
  1. Correspondence to: K E Shipman kate.shipman@doctors.net.uk

This article discusses the most common causes of raised alkaline phosphatase levels in an asymptomatic patient and provides advice on the relevant investigations.

Learning points

If alkaline phosphatase is raised in an asymptomatic patient and serum bilirubin, liver transaminases, creatinine, adjusted calcium, thyroid function, and blood count are normal:

  • 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 γ-glutamyltransferase (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

A 51 year old asymptomatic woman presented to her general practitioner for cascade screening for familial hypercholesterolaemia. Blood tests revealed a normal full blood count, renal function, thyroid function, lipid profile, glucose levels, bone profile, and liver profile except for an isolated increased alkaline phosphatase (ALP) concentration at 171 U/L (reference interval 30-130).

What is the next investigation?

ALP is found in high concentrations in liver, bone, kidney, intestine, and placenta. In adults, circulating ALP is predominantly of hepatic and bony origin. Serum ALP levels increase in pregnancy and by the third trimester can be twofold to fourfold higher as a result of a physiological increase in placental ALP. Reference intervals are age and sex related, gradually increasing from age 40 to 65 years, especially in women, and can be up to threefold to sevenfold higher in rapidly growing adolescents.1 Reference intervals contain 95% of the population, therefore 2.5% of the normal population have values above the upper reference limit. The combined analytical and biological variation for serum ALP is around 8%,1 2 and levels increase by up to 6% if analysis is delayed for 96 hours in samples stored at room temperature.3 For example, …

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