A pt with hepatocellular ca has raised levels of ferritin. What is the most probable cause?
a. Hemochromatosis
b. A1 antitrypsin def
c. Cystic fibrosis
answer: A
Definition
• excessive iron storage causing multiorgan system dysfunction (liver, in particular) with total
body stores of iron increased to 20-40 g (normal 1 g)
Pathology
• primary hemochromatosis
ƒ primarily due to common recessive gene (HFE, 5%); 1/400 patients are homozygotes
ƒ results in ongoing gut absorption of iron despite adequate iron stores
• secondary hemochromatosis
ƒ parenteral iron overload (e.g. transfusions)
ƒ chronic hemolytic anemia: thalassemia, pyruvate kinase deficiency
ƒ excessive iron intake
Clinical Manifestations
• usually presents with trivial elevation in serum transaminases
• liver: cirrhosis (30%), HCC (200x increased risk) – most common cause of death (1/3 of patients)
• pancreas: DM, chronic pancreatitis
• skin: bronze or gray (due to melanin, not iron)
• heart: dilated cardiomyopathy
• pituitary: hypogonadotropic hypogonadism (impotence, decreased libido, amenorrhea)
• joints: arthralgia (any joint, but especially MCP joints), chondrocalcinosis
Investigations
• screening for individuals with clinical features and/or family history (1/4 chance of sibling
having the disease)
ƒ transferrin saturation (free Fe2+/TIBC) >45%
ƒ serum ferritin >400 ng/mL
ƒ HFE gene analysis: 90% of primary hemochromatosis involves C282Y allele, while H63D
and S65C alleles also commonly involved and screened
• liver biopsy (generally used to detect cirrhosis or if potential for other causes of liver disease)
ƒ markers of advanced fibrosis: if any of the following are present at the time of diagnosis →
age >40, elevated liver enzymes, or ferritin >1000
ƒ considered if compound heterozygote and potential other cause of liver injury (e.g. fatty
liver, etc.)
ƒ if C282Y/C282Y and no markers of advanced fibrosis, then biopsy generally not needed
• HCC screening if cirrhosis
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