Snapshot A 42-year-old woman with a history of polycystic ovarian syndrome and diabetes presents to her primary care physician's office for abdominal pain. She reports that she has experienced this for the past few months. On physical exam, her skin is noted to be hyperpigmented. She also has hepatomegaly. Given these findings, her physician sends her for laboratory testing, which shows elevated transaminases, iron, and ferritin. She is scheduled for regular phlebotomy. Introduction Clinical definition hemochromatosis is a disease of iron accumulation, characterized by the classic triad cirrhosis diabetes mellitus skin pigmentation Epidemiology demographics age > 40 detected in men earlier than women women lose iron through menstruation etiology hereditary hemochromatosis secondary causes repeated blood transfusions Pathogenesis ↑ intestinal absorption of iron, leading to iron overload iron accumulation in organs cause end-organ damage Genetics autosomal recessive HFE gene mutation on chromosome 6 C282Y mutation H63D mutation associated with HLA-A3 Presentation Symptoms cirrhosis abdominal pain hepatomegaly jaundice spider angioma palmar erythema diabetes mellitus hyperpigmentation of skin found in late-stage disease "bronze diabetes" arthropathy calcium pyrophosphate deposition in metacarpophalangeal joints hypogonadism gynecomastia lack of body hair systemic symptoms weakness fatigue heart failure Studies Diagnostic testing imaging magnetic resonance imaging (MRI) of the liver to evaluate iron load studies liver biopsy Prussian blue stain detects iron deposition in hepatocytes ↑ liver enzymes iron studies ↑ transferrin saturation > 45% ↑ ferritin ↑ iron ↓ TIBC genetic testing for HFE mutation confirms the diagnosis Diagnostic criteria based on clinical history and exam with ↑ transferrin saturation or ferritin Differential Nonalcoholic fatty liver disease (NAFLD) distinguishing factor increased ferritin levels are also found in NAFLD, but transferrin saturation levels are normal and imaging will not show increased iron deposition in the liver Vibrio vulnificus infection distinguishing factors associated with hemochromatosis and bullous skin lesions associated with exposure to seafood Treatment First-line regular phlebotomy indication to maintain ferritin levels 50-100 mcg/L iron chelation therapy deferasirox deferoxamine deferiprone Second-line liver transplant indication decompensated cirrhosis Complications Hepatocellular carcinoma patients should undergo regular screening Cardiomyopathy dilated > restrictive
QUESTIONS 1 of 3 1 2 3 Previous Next Lab Values Blood Hematologic Cerebrospinal Sweat, Urine, and BMI 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/LFemale: 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/mLFemale: 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/dL2-h postprandial:<120 mg/dL Growth hormone - arginine stimulation Fasting: <5 ng/mLProvocative 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/mm3Female: 3.5-5.5 million mm3 Erythrocyte sedimentation rate (Westergren) Male: 0-15 mm/hFemale: 0-20 mm/h Hematocrit Male: 41%-53%Female: 36%-46% Hemoglobin A1c ≤ 6 % Hemoglobin, blood Male: 13.5-17.5 g/dLFemale: 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/kgFemale: 28-45 mL/kg Red cell Male: 20-36 mL/kgFemale: 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/minFemale: 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 hFemale: 2.0-8.0 mg/24 h 17-Ketosteroids, total Male: 8-20 mg/24 hFemale: 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 ( ) xy AC 7 8 9 ÷ 4 5 6 × 1 2 3 - 0 . = + Sorry, this question is for PEAK Premium Subscribers only Upgrade to PEAK Sorry, this question is for PEAK Premium Subscribers only Upgrade to PEAK You have 100% on this question. Just skip this one for now. Take This Question Anyway (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 Type & Select Correct Answer 1 Chronic inflammation 22% (5/23) 2 Excess iron absorption 70% (16/23) 3 Iron deficiency 4% (1/23) 4 Lead poisoning 4% (1/23) 5 Pregnancy 0% (0/23) M1 Select Answer to see Preferred Response SUBMIT RESPONSE 2