Serum parathyroid hormone-related protein concentrations in patients with hematologic malignancies or solid tumors

Abstract

S. Serum parathyroid hormone-related protein concentrations in patients with hématologie malignancies or solid tumors. Acta EndocrinolThe clinical significance of parathyroid hormone-related protein in humoral hypercalcemia of malignancy was investigated by determining the serum parathyroid hormone-related protein concentrations in 167 normal subjects, 56 patients with hematologic malignancy and 144 patients with solid tumor. Serum parathyroid hormone-related protein was measured with a radioimmunoassay kit that recognizes the C-terminal portion of the molecule. The serum parathyroid hormone-related protein concentrations were 20.2\p=n-\50.8 pmol/l (mean\m=+-\2sd) in normal subjects, and were elevated in 80% of the patients with malignancies with hypercalcemia, including squamous cell carcinoma and adult T cell leukemia. Moreover, two cases of B cell non-Hodgkin's lymphoma with hypercalcemia had high serum parathyroid hormone-related protein concentrations, which varied in parallel with the tumor size during the clinical course. Of 136 patients with solid tumors with normocalcemia, the serum parathyroid hormone-related protein concentration was slightly elevated in only 5.1%, all of whom were at an advanced stage. These data indicate that determination of the serum parathyroid hormone\x=req-\ related protein concentration is useful for differential diagnosis of humoral hypercalcemia of malignancy and prediction of its development. In 1987, four groups (1-4) purified parathyroid hor¬ mone-related protein (PTHrP) and Suva et al. (5) cloned and sequenced the gene of this protein. In addition, immunoreactive PTHrP was demonstrated in an extract of a humoral hypercalcemia of malignancy tumor (6, 7) by radioimmunoassay (RIA). In 1990, Burtis et al. ( 8) developed an immunoradiometric assay (IRMA) for PTHrP (1-74) and an RIA for PTHrP (109-138). and reported that both their assays were useful in the differential diagnosis of hypercalcemia. The value of determining urinary PTHrP (127-141) was also reported (9). However, the serum PTHrP levels in normal subjects are difficult to measure by these assays, and there have been few reports on the relationship between the clinical course and serum PTHrP level.Recently, Kasahara et al. (10) developed an RIA kit for PTHrP (109-141) with which we could measure the serum PTHrP concentrations in normal subjects and in patients with various diseases. Here we report data on the serum PTHrP concentrations in patients with héma¬ tologie malignancies or solid tumors who had normal serum creatinine levels, and the relationship between the clinical course and change in serum PTHrP. Subjects and methods SubjectsThe subjects examined were 167 normal adults (92M, 75F) aged 20-60 years, 56 patients with hématologie malignancy and 144 patients with solid tumor.Serum calcium was measured using the O-cresolphthalein complexing method after an overnight fast. The serum calcium concentration was corrected by the equation, "corrected calcium = measured calcium (mg/ dl) + 4.0-albumin (g/dl)" and valu...

Serum calcium levels are elevated among women with untreated postmenopausal breast cancer

“…However, even early stage breast cancers may be associated with aberrations in calcium homeostasis that are caused by parathyroid hormone-related protein (PTHrP), the agent of humoral hypercalcemia of malignancy [14]. Serum levels of PTHrP, which are known to increase serum levels of calcium, are reported to increase with tumor size in both hematologic and solid tumors [23]. However, if the increase in serum calcium that we observed were due to PTHrP, it might be expected that serum calcium levels would increase with tumor size and stage, which was not observed.…”

Haematological emergencies managing hypercalcaemia in adults and children with haematological disorders

“…In one study (Firkin et al , 1996) PTHrP was elevated in 3/9 myeloma patients and 2/4 non‐Hodgkin lymphoma (NHL) patients with hypercalcaemia. Nakamura et al (1992) identified hypercalcaemia in 7/56 patients with haematological neoplasms. Of these seven patients, four (two with B cell NHL, one with adult T cell leukaemia and one with myeloma) had high serum PTHrP levels (Nakamura et al , 1992).…”

Utility of measuring serum parathyroid hormone-related protein concentration in leukemic patients with hypercalcemia for assessing disease status

“…These findings suggest that the normal leukocyte response to G-CSF affects serum LDH levels, while the serum PTHrP level may better reflect the status of the leukemia. Nakamura et al (12) have reported that the serum PTHrP concentration started to increase in parallel with tumor enlargement and before an increase in serum calcium. Our finding that elevation of the serum PTHrP concentration correlates better with leukemic cell proliferation than with serum calcium concentration indicates that serum PTHrP concentration may be useful in assessing disease status in leukemic patients with hypercalcemia.…”