A patient with severe hypercalcemia in multiple organ dysfunction syndrome: Role of elevated circulating 1α,25(OH)2vitamin D levels

Abstract

A 54-year-old man was transferred to our ICU because of systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction syndrome (MODS). He died after 38 days of intensive care. During treatment, his serum calcium (Ca) levels continued to increase and reached 3.95 mmol/L, while the ionized Ca levels reached 2.30 mmol/L before his death. He presented with severe kidney injury, pancreatitis, and hemorrhagic gastric erosion that worsened his prognosis; these were possibly associated with the hypercalcemia. His circulating 1a,25-dihydroxyvitamin D [1,25(OH) 2 D] level was elevated (75.7 to 204 pg/mL), whereas the levels of 25-hydroxyvitamin D, parathyroid hormone, and parathyroid hormone-related peptide were not. Liver histology revealed immunoreactivity for 25-hydroxyvitamin D 1a-hydroxylase (CYP27B1) in some of the hepatocytes, in which the localization pattern was similar to that of lysozyme-positive hepatocytes. Our ICU has previously encountered 22 similar MODS patients who presented with hypercalcemia over the last 8 years. SIRS with severe kidney and liver injuries are common clinical findings in hypercalcemic patients with MODS. Of the 23 hypercalcemic MODS patients, including the present patient, 17 had circulating 1,25(OH) 2 D levels exceeding 70 pg/mL despite severe kidney injury. Extrarenal activation of CYP27B1 seems to play a role in the development of hypercalcemia in this disease condition. Clinicians need to be aware that severe hypercalcemia may occur in MODS patients. ß

Association of 25‐hydroxyvitamin D levels with liver dysfunction and mortality in chronic liver disease

“…25(OH)D is the main circulating vitamin D metabolite and is used for classification of the vitamin D status . 1‐alpha‐hydroxylase in the kidney converts 25(OH)D to 1,25‐dihydroxyvitamin D (1,25[OH]2D), which has a higher affinity for the vitamin D receptor (VDR) compared to 25(OH)D. Interestingly, local conversion of 25(OH)D to 1,25(OH)2D has recently been observed in many extra‐renal tissues including the liver . Finally, 25(OH)D or 1,25(OH)2D bind to the ubiquitously expressed VDR, which regulates approximately three percent of the human genome .…”

Hypercalcemia in the Intensive Care Unit

“…Seventeen had high 1,25-dihydroxy vitamin D levels with low or normal serum PTH and PTHrP levels. 58 All 23 had the systemic inflammatory immune response syndrome (SIRS) and acute kidney injury, and all were recipients of partial liver transplantation or had severe liver injury.…”