A 60-year-old woman comes to the office due to progressive fatigue over the past 6 months. She has no weight loss, joint pain, hematochezia, vomiting, dyspnea, cold intolerance, anxiety, or depression. Medical history is significant for hyperlipidemia, for which the patient has been taking simvastatin for 5 years. Family history is unremarkable. She does not use tobacco, alcohol, or illicit drugs. Temperature is 37.6 C (99.7 F), blood pressure is 142/80 mm Hg, pulse is 80/min, and respirations are 12/min. Sclera are anicteric and mucosal membranes are moist. Heart and lung sounds are unremarkable. The abdomen is nontender and nondistended. Hepatomegaly is present. Skin and musculoskeletal examinations are unremarkable. Laboratory results are as follows:
| Complete blood count | |
| Hemoglobin | 14.1 g/dL |
| Platelets | 435,000/mm3 |
| Leukocytes | 7,000/mm3 |
| Liver function studies | |
| Albumin | 3.9 g/dL |
| Total bilirubin | 0.7 mg/dL |
| Alkaline phosphatase | 90 U/L |
| Aspartate aminotransferase (SGOT) | 175 U/L |
| Alanine aminotransferase (SGPT) | 192 U/L |
| Blood, plasma, and serum | |
| Ferritin | 1625 ng/mL |
Serology for viral hepatitis is negative. Right upper quadrant ultrasound reveals an enlarged liver with normal echotexture and no evidence of cirrhosis. This patient would most benefit from which of the following?
Hereditary hemochromatosis | |
Clinical manifestations |
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Diagnosis |
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Management |
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This patient has clinical features suggestive of hereditary hemochromatosis (HH), including hepatomegaly, elevated liver transaminases, and a striking elevation in serum ferritin. HH is an autosomal recessive disorder caused by an HFE genetic mutation and is characterized by increased intestinal iron absorption, tissue iron deposition, and ultimately multisystem end-organ damage. HH is most common in men and postmenopausal women; premenopausal women are less severely affected due to menstrual blood (and iron) loss.
Excessive iron stores in HH can be demonstrated by an elevated transferrin saturation (ie, serum iron/total iron binding capacity × 100). The diagnosis is confirmed by testing for HFE genetic mutations.
The treatment of choice is therapeutic phlebotomy, which helps keep ferritin levels low enough to avoid complications. Patients with extreme hyperferritinemia (eg, serum ferritin >1000 ng/mL) must not wait for genetic testing results before receiving urgent phlebotomy because they are at exceptionally high risk for immediate and irreversible end-organ damage (eg, cardiomyopathy, cirrhosis, arthritis, diabetes).
(Choice A) Statins (eg, simvastatin) can cause hepatotoxicity with elevated liver transaminases, but serum ferritin is not affected. Although this patient's statin may be suspended temporarily, either now or in the future if liver enzymes do not normalize, phlebotomy must be initiated immediately.
(Choice B) Autoimmune hepatitis can be treated with prednisone. Although it can cause mild elevations in ferritin, levels typically do not exceed 1000 ng/mL.
(Choice C) Penicillamine is used to treat Wilson disease. This inherited disorder can cause elevated liver enzymes, but clinical manifestations are generally apparent at age <35, and most patients have neuropsychiatric symptoms (eg, psychosis, tremors).
(Choice E) Patients with HH who are at low risk for end-organ damage (eg, ferritin <500 ng/mL, normal liver function tests) may be closely followed with periodic laboratory testing; phlebotomy is initiated if laboratory values worsen or the patient develops symptoms of end-organ damage.
(Choice F) Ursodeoxycholic acid is used to treat primary biliary cholangitis, which presents with fatigue and pruritis. Mild elevations in transaminases may occur, but profound alkaline phosphatase elevations and direct hyperbilirubinemia are more typical findings.
Educational objective:
Hereditary hemochromatosis is characterized by increased intestinal iron absorption, tissue iron deposition, and multisystem end-organ damage (eg, hepatotoxicity). The diagnosis is confirmed by testing for HFE genetic mutations, but patients with extreme hyperferritinemia (eg, serum ferritin >1000 ng/mL) should receive urgent therapeutic phlebotomy without waiting for genetic testing results.