HIGH FERRITIN, PHOSPHATASE, AND CALCIUM

A 47-year-old black man has had elevated ferritin levels ranging from 500-800 ng/mL for the past two years. Physical examination shows nothing out of the ordinary. His rheumatoid profile is negative. C-reactive protein levels and erythrocyte sedimentation rate are normal. Iron saturation is 30%. Liver enzymes are within normal limits. His alkaline phosphatase is 50% above normal. The patient has chronic hypercalcemia (10.5-11.0 mg/dL).

Potassium, parathyroid hormone, urinary calcium and phosphorus, as well as angiotensin converting enzyme (ACE) levels, are normal. Protein electrophoresis is polyclonal. A hemochromatosis gene study was negative. Until five months ago, the patient had been taking lithium for 10 years. How should I proceed?
—Tai J. Kim, MD, Denton, Tex.

The fact that you checked an ACE level leads me to believe that you considered sarcoidosis in the differential diagnosis. Despite your patient’s normal ACE, sarcoidosis remains a possibility since ACE levels are elevated in only 40%-80% of patients with active disease. Sarcoidosis would also account for the hypercalcemia (due to extrarenal production of calcitriol by activated macrophages), the elevated alkaline phosphatase level (result of diffuse granulomatous involvement of the liver), and the polyclonal gammopathy. A chest x-ray would be useful, as 90% of patients with sarcoidosis have lung involvement. I would also determine the source of the elevated alkaline phosphatase. Elevation of either 5'-nucleotidase or g-glutamyltranspeptidase would suggest a hepatic source and warrant ultrasound of the liver. Normal levels of these substances suggest a bony source, and a bone scan would be appropriate. In addition, inquire carefully about other causes of chronic liver disease that can result in a high ferritin level, such as alcoholic and nonalcoholic fatty liver disease and hepatitis B and C (which can also result in a polyclonal gammopathy), and I would check vitamin D levels to further work up the hypercalcemia.
—Susan Kashaf, MD, MPH (115-24)

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