1,25-dihydroxyvitamin D and PTHrP mediated malignant hypercalcemia in a seminoma

Abstract

BackgroundSeminomas have been rarely associated with malignant hypercalcemia. The responsible mechanism of hypercalcemia in this setting has been described to be secondary to 1,25-dihydroxyvitamin D secretion. The relationship with PTHrP has not been determined or studied.The aim of this study is to describe and discuss the case and the pathophysiological mechanisms involved in a malignant hypercalcemia mediated by 1,25-dihydroxyvitamin D and PTHrP cosecretion in a patient with seminoma.Case presentationA 35-year-old man was consulted for assessment and management of severe hypercalcemia related to an abdominal mass. Nausea, polyuria, polydipsia, lethargy and confusion led him to the emergency department. An abdominal and pelvic enhanced CT confirmed a calcified pelvic mass, along with multiple retroperitoneal lymphadenopathy. Chest x-ray revealed “cannon ball” pulmonary metastases. The histopathology result was consistent with a seminoma. Serum calcium was 14.7 mg/dl, PTH was undetectable, 25-dihydroxyvitamin D was within normal values and PTHrP and 1,25-dihydroxyvitamin were elevated (35.0 pg/ml, and 212 pg/ml, respectively). After the first cycle of chemotherapy with bleomycin, etoposide and cisplatin, normocalcemia was restored. Both PTHrP and 1,25-dihydroxyvitamin D, dropped dramatically to 9.0 pg/ml and 8.0 pg/ml, respectively.ConclusionThe association of seminoma and malignant hypercalcemia is extremely rare. We describe a case of a patient with a seminoma and malignant hypercalcemia related to paraneoplastic cosecretion of 1,25-dihydroxyvitamin D and PTHrP. After successful chemotherapy, calcium, PTHrP and 1,25-Dihydroxyvitamin D returned to normal values.

Successful Treatment for Hypercalcemia due to Cosecretion of Parathyroid Hormone-Related Protein and 1,25-Dihydroxyvitamin D3 in Non-Small-Cell Lung Cancer: A Case Report and Literature Review

“…However, calcitriol is rarely secreted from these tumors. Only few previous reports have described elevated levels of both blood serum PTHrP and calcitriol in patients with solid tumors [2][3][4][5][6]. Here, we report the case of a patient with squamous cell lung cancer, who developed hypercalcemia caused by cosecretion of PTHrP and calcitriol, which was improved by corticosteroids.…”

“…To our knowledge, this is a rare case with cosecretion of PTHrP and calcitriol in lung cancer. There are only five previous reports of the cosecretion of PTHrP and calcitriol in cases of solid tumors including ovarian carcinoma, pancreatic neuroendocrine tumor, renal cell carcinoma, seminoma, and lung cancer [2][3][4][5][6], which are summarized in Table 2. In the previous report on lung cancer, the histological type was squamous cell carcinoma [6], as in our case.…”

Hypercalcemia of Malignancy in Thymic Carcinoma: Evolving Mechanisms of Hypercalcemia and Targeted Therapies

“…Hypercalcemia resulting from multiple mechanisms, HHM-CIH and HHM-PTHrP, has been described in rare cases of HTLV-1 positive ATLL [ 5 ], neuroendocrine tumors of the pancreas [ 6 ], seminoma [ 7 ], and ovarian carcinoma [ 8 ]. The mechanism elucidated to cause HHM-SCCBR has been described in conjunction with HHM-PTHrP or OMRH, as observed in multiple myeloma and breast cancer [ 37 , 38 ].…”

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

“…Furthermore, PTHrP activates pathways that enable tumor cells to form bone metastases [1]. Ectopic calcitriol production is a further mechanism of hypercalcemia [12,15,16], sometimes occurring in other tumors as a coexisting mechanism that has to be considered. Further mechanisms include ectopic PTH secretion or cytokine-induced hypercalcemia.…”