INVESTIGATION OF ELEVATED SERUM FERRITIN AND POSSIBLE IRON OVERLOAD
- A raised serum ferritin is a common laboratory abnormality
- Only a minority of pts with an elevated ferritin will have evidence of true iron overload and thus possible haemochromatosis
- Serum ferritin is raised in a variety of conditions with no evidence of actual iron overload
Table 1:
CAUSES OF RAISED SERUM FERRITINConditions with no iron overload / Conditions with true iron excess
1. Any acute inflammation/infection (acute phase reactant)
2. Liver disease eg viral hepatitis, fatty liver*
3. Alcohol excess with or without evidence of liver damage*
4. Chronic inflammatory conditions eg Rheumatoid Athritis, SLE, Inflammatory bowel disease
5. Thyrotoxicosis
6. Malignancy ( very unlikely to manifest as an isolated finding without other obvious clinical or laboratory abnormalities)
7. Familial hyperferritinaemia and cataract syndrome (rare congenital abnormality characterised by early onset cataracts)
IN ALL OF THESE CASES THE SERUM FERRITIN IS NOT A SIGN OF TRUE IRON ACCUMULATION AND DOES NOT REQUIRE FURTHER ACTION. / Primary:
- Hereditary Haemochromatosis
- Transfusion iron overload (chronic marrow failure)
- Ineffective red cell production (eg sideroblastic anaemia, thalassaemia)
- Porphyria cutanea tarda
(*in cases with evidence of liver damage you may need to formally exclude hereditary haemochromatosis - see page 3 )
Hereditary Haemochromatosis (HHC)
Genetic Haemochromatosis is characterised by iron accumulation due to the inheritance of mutations in the HFE gene. In the UK >90% of cases are homozygous for C282Y/C282Y mutation and 4% are compound heterozygotes (C282Y/H63D). Clinical penetrance is highly variable.
Early symptoms are non specific and include weakness, lethargy, abdominal pain and weight loss. Hepatic fibrosis/cirrhosis, diabetes mellitus, impotence and cardiac failure are delayed features of untreated patients.
The diagnosis of HHC should be considered in patients with:
- Unexplained liver disease
- Type II diabetes mellitus especially in those diagnosed at early age +/-abnormal LFTs/hepatomegaly/ early onset sexual dysfunction
- Chronic unexplained fatigue/weakness and abdominal pain
- Early onset athralgia/atypical arthropathy
- Early onset male impotence, early menopause or loss of libido in women
- Early onset arrhythmias and cardiomyopathy
- Asymptomatic individuals with incidental elevated LFTs/hepatomegaly +hyperferritinaemia
- First degree relatives aged >20 yrs of a confirmed case of HHC
In primary care the major concern is usually selecting which patients with a raised serum ferritin need investigating further for haemochromatosis. It is important to appreciate that an elevated ferritin is common in other conditions (see above),typically a late event in haemochromatosis and that true iron overload is preceded by an elevated Transferrin Saturation. This is established by requesting a serum iron and TIBC (Total Iron Binding Capacity) from biochemistry. To improve sensitivity this must be on a FASTING sample.
This document is designed to assist in the investigation of those patients with a raised serum ferritin. Some additional tests are essential before the patient is considered for referral to secondary care. For guidance on the appropriate tests please refer to the additional documentation below and then to the suggested referral pathway for those patients with evidence of true iron overload or those with a combination of equivocal results.
Remember if there is a strong clinical suspicion of haemochromatosis (e.g. family history, unexplained liver disease) you should request a serum Fe/TIBC plus serum ferritin at the outset – the latter may not be raised in early iron loading.
NOTE: GP’s are advised to read the ‘Raised Ferritin flowchart’ first and then the ‘Haemochromatosis referral pathway’ document last, as numbered below.
Dr M. Hamblin, Consultant Haematologist CHUFT, Department of Haematology: Feb 2015