Hypercalcemia due to ectopic PTH

Hypercalcemia is a relatively common clinical problem. Although PHP occurs in only 5% of patients with cancer Primary hyperparathyroidism (PHP) is the most common cause of hypercalcemia in ambulatory patients ( > 90%) while cancer is the major cause in hospitalized patients (>65%) [1]. Humoral hypercalcemia of malignancy can be caused by parathyroid hormone-related protein (PTHrP) or by one of several other secreted molecules. Although PTHrP production explains most cases of humoral hypercalcemia of malignancy, there are exceptions. Recently, we had a patient in our clinic who showed ectopic PTH production by a bladder carcinoma. On admission the patient had signs and symptoms related to hypercalcemia, the most prominent of which were lethargy and confusion. Turgor was slightly diminished. An abdominal and pelvic CT scan disclosed left hydronephrosis and a hydroureter due to a huge tumor of the bladder (6 cm in diameter). There was clear tumor infiltration in the surrounding tissues outside the bladder. No signs of metastatic disease in bones or the liver and no lymph node enlargement were found. The prostate showed calcifications but no direct relation to the tumor. A diagnostic cystoscopic examination revealed a huge, malignant tumor. Histological examination of a biopsy specimen showed poorly differentiated squamous cell carcinoma of the bladder (pT3G3). Molecular analysis to detect PTHmRNAwas not possible as there was no frozen tumor tissue available. Immunohistochemical analysis with anti-PTH and anti-calcitonin antibodies had been performed using formalin-fixed, paraffinembedded sections of the tumor, but this failed to provide positive staining results. The albumin-corrected calcium value was greater than 3.5 mmol/l and the serum intact parathyroid hormone (PTH) concentration, measured by immunochemiluminometric assay (ICMA), was extremely high: 116 pmol/l (N=0.6–6.7 pmol/l). Cross-reactivity with PTHrP was excluded. Such an elevation of PTH usually indicates the presence of PHP, malignant disease, or lithium administration. Our patient was not taking lithium.