Poster Presentation ESA-SRB 2023 in conjunction with ENSA

A rare case of hypercalcaemia secondary to advanced chronic liver disease (#354)

Rachael Zuzek 1 , Tegan Van Gemert 1 , Jane Zhang 1
  1. Wollongong Hospital, Figtree, NSW, Australia

Background: Hypercalcaemia in patients with chronic liver disease (CLD) without hepatocellular carcinoma (HCC) is rare and a diagnosis of exclusion.

Case: A 30-year-old previously well male initially presented with severe COVID pneumonitis, complicated by secondary sclerosing cholangitis resulting in CLD. He developed new hypercalcaemia which correlated with increasing liver enzymes and bilirubin (peak 278µmol/L). Peak corrected calcium (CorCa) was 3.47mmol/L with suppressed PTH 1.0pmol/L. There was no personal/family history of calcium disorders and no contributing medications. There was no bony abnormality or underlying malignancy on imaging; AFP was negative. IgG was mildly raised with no other features consistent with myeloma. He had normal renal and thyroid function. His urine calcium-to-creatinine ratio was normal. Vitamin D toxicity was excluded with a low vitamin D 27nmol/L. 1,25-dihyroxyvitamin-D was undetectable <12pmol/L and ACE was normal, ruling out granulomatous disease. There was no prolonged immobilisation. IV pamidronate and rehydration lead to initial improvement, however, his hypercalcaemia recurred (CorCa 2.7-3.12mmol/L). After successful liver transplantation his hypercalcaemia fully resolved and remained normal months later, leading to the diagnosis of hypercalcaemia of CLD.

Discussion: CLD is more often associated with hypocalcaemia due to hypoalbuminaemia. Hypercalcaemia in CLD associated with and without HCC was first described by Gerhadt in 1987 [1]. There are few reported cases and the cause is not clear. Elevated inflammatory markers (eg: TNF-1, IL-1) [2] and hyperbilirubinaemia may lead to upregulation of RANKL/OPG which increases bone resorption and downregulation of osteogenic factors such as RUNX2 [3]. Whether bilirubin is pathogenic or an indicator of disease severity is not certain [4]. CLD may also impair catabolism of metabolites involved in bone resorption [4]. The hypercalcaemia can be transient and responds to bisphosphonates and hydration [2,5], and in advanced cases, resolves with liver transplantation. Further research is needed to understand this rare cause of hypercalcaemia.

  1. [1] Gerhadt A, Greenberg A, Reilly J, Van Thiel D. Hypercalcaemia: a complication of advanced chronic liver disease. Arch Intern Med. 1987;147:274-277.
  2. [2] Ragate D, Taneja S, Roy A et al. Idiopathic hypercalcaemia in decompensated cirrhosis: reexploring an entity in oblivion. Journal of Clinical and Experimental Hepatology. 2021;11(2):270-272.
  3. [3] Zulfikar R, Silodia A. Hypercalcaemia in chronic liver disease: a rare entity. American Journal of Gastroenterology. 2013;108:s354.
  4. [4] Marius C, Fillaus J, Groggel G. A rare case of liver disease induced hypercalcemia. Case presentation and review of the literature. The Internet Journal of Nephrology. 2008;5(1)
  5. [5] Kuchay M, Mishra S, Farooqui K et al. Hypercalcaemia of advanced chronic liver disease: a forgotten clinical entity! Clinical Cases in Mineral and Bone Metabolism. 2016;13(1):15-18.