Association of primary hyperparathyroidism and humoral hypercalcemia of malignancy in a patient with clear cell renal carcinoma

Abstract

SUMMARYHypercalcemia is found frequently in patients with cancer. Besides the etiology related to the malig nancy, other causes should be considered in the differential diagnostic, as primary hyperparathyroid ism, granulomatous diseases and the use of thiazide diuretics. We present a case report of a severe hypercalcemia due to a rare association and review the relevant literature. A female patient, 57 years old, sent to the Endocrinology Service of Hospital das Clínicas da Universidade do Paraná (SEMPR) in order to investigate severe hypercalcemia with frequent need of hospitalization. The patient was in chemotherapy treatment for recurrence of clear cell renal cancer. During the investigation she presen ted high level of parathyroid hormone (PTH) and parathyroid scintigraphy suggestive of hyperplasia/ adenoma of parathyroid, histopathological diagnosis was confirmed after parathyroidectomy. After surgery the patient presented undetectable levels of PTH. However, she continued with progressive increase of serum calcium, with no signs of bone metastases or change in vitamin D metabolism. The investigation showed high levels of PTHrelated protein (PTHrP), leading us to the diagnosis of hypercalcemia of malignancy. The patient presented severe hypercalcemia due to the rare association of primary hyperparathyroidism and humoral hypercalcemia of malignancy due to secretion of PTHrP by tumor cells. The presence of isolated primary hyperparathyroidism, as a cause of hypercalcemia in cancer patients, has been described in approximately 510% of the patients. However, the association of primary hyperparathyroidism and humoral hypercalcemia of malignancy (which means with con comitant elevation of PTH and PTHrP) is rare, only three cases have been described in the literature.

Cancer-Related Hypercalcemia

“…29 There are also reports of concurrent primary hyperparathyroidism and humoral hypercalcemia of malignancy. [30][31][32] WORK-UP Obtaining a serum calcium is the first step in the work-up of suspected hypercalcemia. Total serum calcium, which measures both bound and unbound calcium, is most commonly used.…”

Ovarian cancer presenting with hypercalcemia: two cases with similar manifestations but different mechanisms

“…PTH-mediated hypercalcemia is another common cause, in addition to PTHrP-induced HHM. Although ectopic hyperparathyroidism caused by tumor cells is extremely rare, primary hyperparathyroidism, due to parathyroid adenoma or hyperplasia, occurs more frequently 15 . Related research has shown that 8 cases of 133 patients with cancer-related hypercalcemia were caused by primary hyperparathyroidism 16 .…”

Pazopanib as salvage therapy in metastatic renal cell carcinoma with hypercalcemic crisis and renal insufficiency: a case report and literature review

“…Furthermore, about 40% of patients with locoregional RCC experience recurrence and develop metastasis after surgery ( 1 , 2 ). Up to 20–30% of metastatic RCC (mRCC) patients present with hypercalcemia and renal function failure, but only 1.6% patients experience crisis ( 3 , 4 ). Some systemic symptoms resulting from metastatic disease, such as fever, weight loss, anemia, local bone pain, and pulmonary symptoms have been associated with a poor prognosis.…”