The Asymptomatic Iron

Elise Krejci

A 65-year-old Caucasian male presented to his primary care physician for a routine physical exam prior to retiring. He had enjoyed excellent health throughout his life, and did not report any new symptoms at the time. His past medical history included elevated prostate-specific antigens that had been evaluated with multiple negative prostate needle biopsies, and hypercholesterolemia treated with diet and medication. Family history was notable for cardiovascular disease, hypertension, and breast cancer. He did not smoke, and consumed less than one beer or glass of wine per week. On direct questioning, he did not acknowledge chest pain, shortness of breath, arthralgias, fatigue, cold intolerance, or decreased libido.

Physical exam showed a healthy-appearing white male weighing 208 lb with a blood pressure of 147/81 and a regular pulse of 72 bpm. Head, eye, ear, nose, throat (HEENT) exam was unremarkable. Heart and lung exams were normal. The abdominal exam was unremarkable with no evidence of hepatosplenomegaly. Scrotal exam showed normal testes. Skin exam showed normal distribution of a summer tan and male pattern facial and body hair.

His internist ordered the following laboratory studies as part of a general health screening:

Reference

Reference

Value,

Interval,

Interval,

Conventional

Conventional

Value,

Conventional

Analyte

Units

Units

SI Units

Units

WBC

8.2 x 103/mL

4-11

8.2 x 109/L

4-11

Hemoglobin

15.2 g/dL

13.5-16.5

152 g/L

135-165

Platelet count

297 x 103/mL

140-400

297 x 109/L

140-400

aPTT

28 s

23-36

Same

Prothrombin time

13.2 s

11-15.5

Same

Glucose

119 mg/dL

70-110

6.6 mmol/L

3.9-6.1

Creatinine

0.7 mg/dL

0.7-1.2

62 mmol/L

62-106

Protein, total

7.9 g/dL

6-8

79 g/L

60-80

Albumin

3.8 g/dL

3.5-5.0

30 g/L

35-50 g/L

Bilirubin, total

0.5 mg/dL

0.2-1.2

8.6 mmol/L

3-21

Alkaline phosphatase

42 U/L

35-120

0.71 mkat/L

ALT AST

Serum iron Total iron binding capacity Transferrin saturation Ferritin

Value, Conventional Units

Reference Interval, Conventional Units

Value, SI Units

Reference Interval, Conventional Units

8-47 10-42 45-160 220-420

0.71 fraction 0.21-0.50

450 ng/mL

20-323 450 mg/L

20-323

Serum iron and total iron binding capacity (TIBC) were repeated on a morning blood specimen after overnight fasting: iron 194 mg/mL, TIBC 298 mg/mL, and transferrin saturation 65%. Hepatitis B and C serologies were negative.

The patient was referred to a hematologist, who recommended a liver biopsy to confirm and quantify excess tissue iron deposition and to assess liver damage due to mildly elevated transaminases. Steatosis and mild portal inflammation, but no fibrosis or architectural abnormalities were seen on trichrome and reticulin stains. In addition, there was moderate periportal and pericanalicular iron deposition, primarily in the hepato-cytes. The total liver iron was reported as 4896 units (normal = 200-2400) and the hepatic iron index was 1.3. Molecular diagnostic testing for the two most common HFE gene mutations associated with hereditary hemochromatosis was performed, and the patient was compound heterozygous for a mutation that coded for substitution of tyrosine for cysteine at amino acid 282 (C282Y), and a second mutation that coded for substitution of aspartate for histidine at amino acid 63 (H63D).

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