Hypercalcemia of malignancy in metastatic esophageal squamous cell carcinoma with simultaneous PTHrP and calcitriol overproduction: A case report with literature review

Abstract

Introduction and importance hypercalcemia of malignancy is a severe complication of malignancy and associated with poor prognosis. Four mechanisms are implicated in this metabolic disorder, including excess parathyroid-related peptide secretion, focal osteolysis secondary to bone metastasis or multiple myeloma, excess calcitriol production, and ectopic parathyroid hormone production. Humoral hypercalcemia of malignancy secondary to isolated PTHrP or calcitriol overproduction is known; however, hypercalcemia of malignancy due to simultaneous PTHrP and calcitriol overproduction is less well known. Case presentation we report a case of a 63-year-old male who was diagnosed with poorly differentiated esophageal squamous cell carcinoma with simultaneous PTHrP and calcitriol overproduction. Clinical discussion while hypercalcemia of malignancy secondary to simultaneous PTHrP and calcitriol secretion has been reported in other solid cancers, this is the first case of humoral hypercalcemia of malignancy secondary to simultaneous PTHrP and calcitriol secretion associated with esophageal cancer. This phenomenon deserves increased recognition as it has both diagnostic and therapeutic consequences. We discuss the current testing algorithm and its limitations in determining the etiology of hypercalcemia of malignancy since it may miss the diagnosis of simultaneous PTHrP and calcitriol production. Conclusion we propose a revised testing algorithm for hypercalcemia of malignancy, which may improve the identification of simultaneous overproduction of PTHrP and calcitriol. This new algorithm can better characterize the mechanisms of hypercalcemia of malignancy and more appropriately guide treatment.

An Exciting Case of Acute on Chronic Hypercalcemia in the Setting of Chronic Primary Hyperparathyroidism: A Case Report and Diagnostic Approach

“…When utilizing the diagnostic algorithm for hypercalcemia (Figure 1 ), it is crucial to consider the patient’s presentation, including the absence or presence of B-symptoms [ 6 , 7 ]. In our patient, the only symptoms noted on admission were that of hypercalcemia, and no B-symptoms were acknowledged.…”

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Hypercalcemia in Cancer: Causes, Effects, and Treatment Strategies

“…PTHrP, in contrast to PTH, does not influence the 1,25-dihydroxycholecalciferol production [51,56]; therefore, it does not affect intestinal absorption of calcium and phosphorus [4]. However, cases of hypercalcemia with simultaneous overproduction of PTHrP and 25(OH)D have been occasionally reported [57]. Hypercalcemia linked to humoral or local overproduction of PTHrP usually occurs in neoplasms.…”