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Humoral Hypercalcemia in a Patient with Cholangiocellular Carcinoma – Effective Therapy with Denosumab

Unusual clinical course, Challenging differential diagnosis, Unusual or unexpected effect of treatment, Educational Purpose (only if useful for a systematic review or synthesis)

Igor Alexander Harsch, Peter Christopher Konturek

Department of Internal Medicine II, Division of Endocrinology and Metabolism, Thuringia Clinic Saalfeld, Saalfeld/Saale, Germany

Am J Case Rep 2019; 20:1325-1330

DOI: 10.12659/AJCR.917275

Available online:

Published: 2019-09-07


BACKGROUND: Hypercalcemia in cholangiocellular carcinoma is a highly uncommon event, mainly reported in Asian patients. In the absence of bone metastases, humoral hypercalcemia of malignancy (HHM) can be assumed. This is mostly the consequence of an elevated parathormone-related peptide (PTHrP) level. The standard therapeutic options in HHM are sometimes limited by the underlying disease or concomitant diseases.
CASE REPORT: We report the case of a 65-year-old Caucasian male. A syncope due to a hypercalcemia of 4.16 mmol/L (normal range, 2.19-2.54 mmol/L) was the initial symptom that eventually led to the diagnosis of cholangiocellular carcinoma. He had no metastatic bone disease; HHM was suspected. PTHrP was moderately elevated. Since there were contraindications for the standard therapeutic options, a therapy with 120 mg denosumab was initiated and proved effective, safe, and restored the patient’s quality of life for 11 months.
CONCLUSIONS: The moderate elevation of parathyroid hormone-related peptide (PTHrP) in this case is addressed in context with the recent insights of a substantial underestimation of this parameter by many commercial assays which can explain our observation. Denosumab, a human monoclonal antibody which acts as a RANKL-inhibitor (receptor activator of nuclear factor kappaB ligand) was recently suggested as a therapeutic alternative. In this case, the therapy of the hypercalcemia with denosumab due to contraindications for other therapies led to an effective and long-standing remission of hypercalcemia. Its effectivity should be studied in larger case samples.

Keywords: Cholangiocarcinoma, Hypercalcemia, Parathyroid Hormone



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