Updated: 11/4/2018

Hemochromatosis

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Snapshot
  • A 43-year-old man presents to a primary care physician for the first time complaining of worsening joint pain and decreased libido over the past two years. Basic laboratory workup reveals hyperglycemia. On physical exam, the patient is noted to have a bright tan despite his work as a radiologist. 
Introduction
  • Disease caused by excess iron deposition in nearly all tissues
    • slow disease course with disease presenting in fifth decade (men)
      • appears 10-20 years post-menopause in women
        • see Treatment section
  • May be primary or secondary
    • primary
      • mutation in HFE gene 
        • gene normally controls loading of iron onto transferrin
      • loss of HFE results in dysregulation leading to a maximual transfer of iron from gut mucosal cells into the plasma 
      • may also have a mutation in
        • ferroportin
        • hemojuvulin
    • secondary (hemosiderosis)
      • accumulation of iron secondary to
        • frequent blood transfusions
          • seen in RBC disorders (e.g. sickle cell, thalassemia)
        • alcoholism
          • high iron content in alcohol
        • drinking water sourced from iron pipes
  • Iron is not directly toxic to tissues
    • iron generates free radicals that causes damage
  • AR inheritance on chromosome 6
    • associated with HLA-A3
    • men > women
    • northern Europeans
Presentation
  • Symptoms
    • cirrhosis
    • malabsorption
      • secondary to destruction of the exocrine pancreas
    • amenorrhea/↓ libido
      • secondary to hypogonadism
    • arthritis
      • chondrocalcinosis
  • Physical exam
    • diabetes mellitus
      • secondary to destruction of the endocrine pancreas
    • skin hyperpigmentation
      • "bronze diabetes"
Evaluation
  • Labs
    • ↑ ferritin
    • ↑ iron
    • ↑ transferrin saturation 
    • ↓ TIBC
      • secondary to ↓ transferrin synthesis
    • ↓ LH/FSH
  • Biopsy
    • micronodular cirrhosis
Treatment
  • Medical
    • repeated phlebotomy
      • ↓ total iron stores
      • menses serves this function in women with HFE mutation
        • reason why disease appears post-menopause
    • deferoxamine
      • iron chelating agent
Prognosis, Prevention, and Complications
  • Complicated by  
    • cardiomyopathy due to iron deposition in the heart
      • initially presents with restrictive symptoms
      • later progresses to dilated cardiomyopathy (most common presentation)
    • CHF
    • ↑ risk of hepatocellular carcinoma 
 

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Questions (3)
Lab Values
Blood, Plasma, Serum Reference Range
ALT 8-20 U/L
Amylase, serum 25-125 U/L
AST 8-20 U/L
Bilirubin, serum (adult) Total // Direct 0.1-1.0 mg/dL // 0.0-0.3 mg/dL
Calcium, serum (Ca2+) 8.4-10.2 mg/dL
Cholesterol, serum Rec: < 200 mg/dL
Cortisol, serum 0800 h: 5-23 μg/dL //1600 h:
3-15 μg/dL
2000 h: ≤ 50% of 0800 h
Creatine kinase, serum Male: 25-90 U/L
Female: 10-70 U/L
Creatinine, serum 0.6-1.2 mg/dL
Electrolytes, serum  
Sodium (Na+) 136-145 mEq/L
Chloride (Cl-) 95-105 mEq/L
Potassium (K+) 3.5-5.0 mEq/L
Bicarbonate (HCO3-) 22-28 mEq/L
Magnesium (Mg2+) 1.5-2.0 mEq/L
Estriol, total, serum (in pregnancy)  
24-28 wks // 32-36 wks 30-170 ng/mL // 60-280 ng/mL
28-32 wk // 36-40 wks 40-220 ng/mL // 80-350 ng/mL
Ferritin, serum Male: 15-200 ng/mL
Female: 12-150 ng/mL
Follicle-stimulating hormone, serum/plasma Male: 4-25 mIU/mL
Female: premenopause: 4-30 mIU/mL
midcycle peak: 10-90 mIU/mL
postmenopause: 40-250
pH 7.35-7.45
PCO2 33-45 mmHg
PO2 75-105 mmHg
Glucose, serum Fasting: 70-110 mg/dL
2-h postprandial:<120 mg/dL
Growth hormone - arginine stimulation Fasting: <5 ng/mL
Provocative stimuli: > 7ng/mL
Immunoglobulins, serum  
IgA 76-390 mg/dL
IgE 0-380 IU/mL
IgG 650-1500 mg/dL
IgM 40-345 mg/dL
Iron 50-170 μg/dL
Lactate dehydrogenase, serum 45-90 U/L
Luteinizing hormone, serum/plasma Male: 6-23 mIU/mL
Female: follicular phase: 5-30 mIU/mL
midcycle: 75-150 mIU/mL
postmenopause 30-200 mIU/mL
Osmolality, serum 275-295 mOsmol/kd H2O
Parathyroid hormone, serume, N-terminal 230-630 pg/mL
Phosphatase (alkaline), serum (p-NPP at 30° C) 20-70 U/L
Phosphorus (inorganic), serum 3.0-4.5 mg/dL
Prolactin, serum (hPRL) < 20 ng/mL
Proteins, serum  
Total (recumbent) 6.0-7.8 g/dL
Albumin 3.5-5.5 g/dL
Globulin 2.3-3.5 g/dL
Thyroid-stimulating hormone, serum or plasma .5-5.0 μU/mL
Thyroidal iodine (123I) uptake 8%-30% of administered dose/24h
Thyroxine (T4), serum 5-12 μg/dL
Triglycerides, serum 35-160 mg/dL
Triiodothyronine (T3), serum (RIA) 115-190 ng/dL
Triiodothyronine (T3) resin uptake 25%-35%
Urea nitrogen, serum 7-18 mg/dL
Uric acid, serum 3.0-8.2 mg/dL
Hematologic Reference Range
Bleeding time 2-7 minutes
Erythrocyte count Male: 4.3-5.9 million/mm3
Female: 3.5-5.5 million mm3
Erythrocyte sedimentation rate (Westergren) Male: 0-15 mm/h
Female: 0-20 mm/h
Hematocrit Male: 41%-53%
Female: 36%-46%
Hemoglobin A1c ≤ 6 %
Hemoglobin, blood Male: 13.5-17.5 g/dL
Female: 12.0-16.0 g/dL
Hemoglobin, plasma 1-4 mg/dL
Leukocyte count and differential  
Leukocyte count 4,500-11,000/mm3
Segmented neutrophils 54%-62%
Bands 3%-5%
Eosinophils 1%-3%
Basophils 0%-0.75%
Lymphocytes 25%-33%
Monocytes 3%-7%
Mean corpuscular hemoglobin 25.4-34.6 pg/cell
Mean corpuscular hemoglobin concentration 31%-36% Hb/cell
Mean corpuscular volume 80-100 μm3
Partial thromboplastin time (activated) 25-40 seconds
Platelet count 150,000-400,000/mm3
Prothrombin time 11-15 seconds
Reticulocyte count 0.5%-1.5% of red cells
Thrombin time < 2 seconds deviation from control
Volume  
Plasma Male: 25-43 mL/kg
Female: 28-45 mL/kg
Red cell Male: 20-36 mL/kg
Female: 19-31 mL/kg
Cerebrospinal Fluid Reference Range
Cell count 0-5/mm3
Chloride 118-132 mEq/L
Gamma globulin 3%-12% total proteins
Glucose 40-70 mg/dL
Pressure 70-180 mm H2O
Proteins, total < 40 mg/dL
Sweat Reference Range
Chloride 0-35 mmol/L
Urine  
Calcium 100-300 mg/24 h
Chloride Varies with intake
Creatinine clearance Male: 97-137 mL/min
Female: 88-128 mL/min
Estriol, total (in pregnancy)  
30 wks 6-18 mg/24 h
35 wks 9-28 mg/24 h
40 wks 13-42 mg/24 h
17-Hydroxycorticosteroids Male: 3.0-10.0 mg/24 h
Female: 2.0-8.0 mg/24 h
17-Ketosteroids, total Male: 8-20 mg/24 h
Female: 6-15 mg/24 h
Osmolality 50-1400 mOsmol/kg H2O
Oxalate 8-40 μg/mL
Potassium Varies with diet
Proteins, total < 150 mg/24 h
Sodium Varies with diet
Uric acid Varies with diet
Body Mass Index (BMI) Adult: 19-25 kg/m2
Calculator

(M1.GI.202) A 63-year-old female enrolls in a research study evaluating the use of iron studies to screen for disease in a population of post-menopausal women. Per study protocol, past medical history and other identifying information is unknown. The patient's iron studies return as follows:

Serum iron: 200 µg/dL (normal 50–170 µg/dL)
TIBC: 220 µg/dL (normal 250–370 µg/dL)
Transferrin saturation: 91% (normal 15–50%)
Serum ferritin: 180 µg/L (normal 15-150 µg/L)

Which of the following is the most likely cause of these findings? Review Topic

QID: 106248
1

Chronic inflammation

22%

(4/18)

2

Excess iron absorption

67%

(12/18)

3

Iron deficiency

6%

(1/18)

4

Lead poisoning

6%

(1/18)

5

Pregnancy

0%

(0/18)

M1

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PREFERRED RESPONSE 2
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