Hypercalcemia of Malignancy Attributed to Cosecretion of PTH and PTHRP in Lung Adenocarcinoma

Abstract

Introduction: Hypercalcemia of malignancy (HCM) portends a very poor prognosis, and no established guidelines exist regarding its management. Most instances of HCM are due to local osteolysis or secretion of parathyroid hormone related-peptide, while less than 1% of all cases are due to ectopic secretion of parathyroid hormone.

Case report: We present an unusual case of HCM due to proposed cosecretion of both parathyroid hormone and parathyroid hormone-related protein in a 36-year-old man with a poorly differentiated lung adenocarcinoma. The patient's hypercalcemia was refractory to conventional measures, including intravenous bisphosphonate therapy (zoledronic acid), and was improved with administration of denosumab.

Conclusion: This is the youngest and first case of hypercalcemia of malignancy attributed to cosecretion of PTH and PTHrP from an adenocarcinoma. In refractory cases of HCM, denosumab is a potential option when other conventional measures are unsuccessful.

Keywords: 1,25 vitamin D, 1,25-dihydroxy vitamin D; HCM, hypercalcemia of malignancy; HD, hospital day; Hypercalcemia of malignancy; PTH, parathyroid hormone; PTHrP, parathyroid hormone-related peptide; ZA, zoledronic acid; cosecretion of PTH and PTHrP; ectopic PTH; hypercalcemia of malignancy.

Fig. 1

Tissue from a brain metastasis resected a month prior to admission, showing positive nuclear staining for PTHrP (dark brown). Paraffin sections were dewaxed, rehydrated, and antigen retrieval was performed in 10 mM sodium citrate, pH 6.0, for 10 minutes using an electric pressure cooker. Sections were cooled, blocked with 3% hydrogen peroxide, then for endogenous biotin (Biocare Medical Kit #AB972), and incubated with 10% goat serum. Rabbit polyclonal antibody to PTHrP (sc-20728; Santa Cruz Biotechnology, Santa Cruz, CA) was used at 1:200 with overnight incubation at 4^oC. PTHrP antibody binding was detected using the Vectastain Elite ABC HRP Kit (Vector Labs, Burlingame, CA) and developed with Dako Liquid DAB substrate (Dako Corp, Carpinteria, CA). PTHrP = parathyroid hormone-related peptide.

Fig. 2

Time course of serum calcium levels prior to and in response to different treatments during hospitalization. The serum calcium trend is illustrated graphically with the various treatment measures the patient received throughout. Please note that the patient received doses of calcitonin on HD#10, 11, 12, 14, and 15, which are not represented in this figure. HD = hospital day.