Hypercalcemia and Overexpression of CYP27B1 in a Patient With Nephrogenic Systemic Fibrosis: Clinical Vignette and Literature Review

Authors

  • Vivian Y Pao,

    1. Endocrine-Metabolism Section, Department of Veterans Affairs Medical Center, University of California, San Francisco, California, USA
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  • Sandra Chang,

    1. Endocrine-Metabolism Section, Department of Veterans Affairs Medical Center, University of California, San Francisco, California, USA
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  • Dolores M Shoback,

    1. Endocrine-Metabolism Section, Department of Veterans Affairs Medical Center, University of California, San Francisco, California, USA
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  • Daniel D Bikle

    Corresponding author
    1. Endocrine-Metabolism Section, Department of Veterans Affairs Medical Center, University of California, San Francisco, California, USA
    • Address correspondence to: Daniel Bikle, MD, PhD, Endocrine Unit, 111N, VA Medical Center, 4150 Clement Street, San Francisco, CA 94121, USA
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  • The authors state that they have no conflicts of interest.

  • Published online on December 29, 2008

Abstract

Nephrogenic systemic fibrosis (NSF) is a disease of thickened, hard, hyperpigmented skin lesions with or without systemic fibrosis occurring in patients with renal insufficiency and associated with the administration of gadolinium-containing contrast. The pathogenesis of this disease is unclear, and there is no definitive treatment. We describe a 71-yr-old patient with stable chronic lymphocytic leukemia (CLL), end-stage renal disease (ESRD), and NSF who presented with hypercalcemia in 2006. Before onset of renal insufficiency in 2002, serum calcium, phosphorus, and PTH levels were normal. In 2004, the patient began hemodialysis, and he was diagnosed with NSF in 2005, shortly after undergoing an MRI with gadolinium contrast administration. Over the next 6 mo, albumin-corrected serum total calcium levels rose from 9.9 to 13.1 mg/dl (normal range, 8.5–10.5 mg/dl) with normal serum phosphorus levels. On admission in September 2006, 1,25-dihydroxyvitamin D [1,25(OH)2D] levels were elevated at 130.7 pg/ml (normal range, 25.1–66.1 pg/ml). Biopsy of an NSF lesion showed increased 25-hydroxyvitamin D3–1-α hydroxylase (CYP27B1) immunostaining compared with the biopsy from a normal control. This is the first reported association of NSF with hypercalcemia caused by elevated 1,25(OH)2D levels. This metabolic disturbance should be sought in future cases to determine a connection between NSF, 1,25(OH)2D metabolism, and CYP27B1 activation in the skin, which may shed light on the pathogenesis of this unusual local and systemic fibrosing disorder.

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