Serum Parathyroid Hormone-related Protein Research Articles

Parathyroid Hormone-Related Protein and Serum Calcium in Patients with Renal Cell Carcinoma

Objective: To evaluate serum parathyroid hormone-related protein (PTHrP) in relation to serum calcium and clinical outcome of patients with renal cell carcinoma.Methods: Sera from 243 patients with renal cell carcinoma were collected prior to therapy. Serum PTHrP was analyzed using an immunoradiometric assay. Tumour stage, nuclear grade, corrected serum calcium, and survival were assessed. Results: Serum PTHrP was detectable in 37/243 sera (15%) and hypercalcaemia (≧2.60 mmol/l) in 32/220 (15%). A positive correlation between serum PTHrP and serum calcium was found (r = 0.326; p < 0.01). Following subdivision of the material, based on storage time, the frequency of detectable serum PTHrP seemed to decrease with time. Serum calcium, but not serum PTHrP, was correlated to tumour stage (p < 0.001). Survival was similar for patients with detectable and undetectable PTHrP, but those with hypercalcaemia had a significantly shorter survival time compared to those with normal serum calcium (p < 0.001). A multivariate analysis showed that tumour stage and serum calcium were independent prognostic factors, but not grade or PTHrP. Conclusions: A positive relation of serum PTHrP to serum calcium was demonstrated in patients with renal cell carcinoma. Hypercalcaemia but not serum PTHrP predicted a worse prognosis.

Laryngeal squamous cell carcinoma with ectopic production of granulocyte colony-stimulating factor and parathyroid hormone-related protein

It is known that malignant tumors occasionally produce hormone-like substances. However, they rarely produce two or more kinds of hormonal factors simultaneously. We describe the clinical, biochemical, and immunohistochemical findings in a patient with squamous cell carcinoma of the larynx associated with leukocytosis and hypercalcemia, without bone metastasis. The serum granulocyte colony-stimulating factor (G-CSF) level was 222 pg/ml (normal, < 38 pg/ml), and decreased to 15 pg/ml after surgery. The serum parathyroid hormone-related protein (PTHrP) level was 5.6 pmol/l (normal, < 0.5 pmol/l), and this also decreased, to less than 0.5 pmol/l. G-CSF and PTHrP increased again with tumor recurrence. The production of G-CSF from the tumor was confirmed by immunohistochemical staining with monoclonal antibody against human recombinant G-CSF. The tumor was revealed to produce both G-CSF and PTHrP. In this article, we describe this very rare case of primary squamous cell carcinoma of the head and neck with the simultaneous ectopic production of more than one hormone-like substance.

Metastatic Medulloblastoma Presented with Hypercalcemia: A Rare Case

Parathyroid hormone related protein (PTH-rP) is the major mediator of humoral hypercalcemia of malignancy which is elevated in most patients with humoral hypercalcemia of malignancy. We report a patient with medulloblastoma presenting with hypercalcemia associated with elevated PTH-rP level. Thus, PTH-rP may play a significant role in hypercalcemia in patients with metastatic medulloblastoma. To the best of our knowledge, this is the first reported case of a PTH-rP secreting metastatic medulloblastoma. We illustrate dramatic changes in serum calcium, parathormone and PTH-rP levels after chemotherapy and radiothrerapy.

Parathyroid hormone-related protein measured at the time of first visit is an indicator of bone metastases and survival in lung carcinoma patients with hypercalcemia.

Parathyroid hormone-related protein (PTH-rP) is a major cause of tumor-induced hypercalcemia (TIH) and frequently is found to be elevated in serum of patients with TIH. In the current study, the authors examined the usefulness of PTH-rP measurement at the time of first presentation in the follow-up of lung carcinoma patients with TIH. The authors retrospectively studied 23 of 1149 lung carcinoma patients who were found to have TIH at the time of first presentation for the correlation between serum PTH-rP and the development of bone metastases and survival compared with lung carcinoma patients without TIH who were matched by gender, age, Eastern Cooperative Oncology Group performance status, histological type of tumor, and stage of the disease. Twenty-three lung carcinoma patients with TIH demonstrated significantly increased serum levels of PTH-rP (mean +/- standard error [SE], 84.1 +/- 16.5 pmol/L) compared with control patients without TIH (mean +/- SE, 36.2 +/- 2.0 pmol/L) at the time of first presentation, (P < 0.001). In these hypercalcemic patients, patients whose serum PTH-rP was > 150 pmol/L (n = 16) were found to have a significantly increased rate of bone metastases (71.4% vs. 12.5%; P = 0.01) and decreased survival (median survival of 1.4 months vs. 5.4 months; P < 0.015) compared with patients whose serum PTH-rP was < 150 pmol/L (n = 7). The data from the current study suggest that serum PTH-rP as determined at the time of first presentation is a useful indicator of not only hypercalcemia but also bone metastasis and eventual survival in patients with lung carcinoma.

Parathyroid hormone-related protein as a novel tumor marker in pancreatic adenocarcinoma.

Parathyroid hormone-related protein (PTHrP) can act as an oncoprotein to regulate the growth and proliferation of many common malignancies, including pancreatic cancer. Previous studies have shown that PTHrP is produced by human pancreatic cancer cell lines, can be shown in the cytoplasm and nucleus of paraffin-embedded pancreatic adenocarcinoma tumor specimens, and is secreted into the media of cultured pancreatic adenocarcinoma cells. We hypothesized that PTHrP could serve as a tumor-marker for growth of pancreatic cancer in vivo. To test this hypothesis, we used an orthotopic model developed in our laboratory of the PTHrP-producing human pancreatic cancer line, BxPC-3. This tumor was stably transduced with green fluorescence protein (GFP) to facilitate visualization of tumor growth and metastases. At early (5 weeks) and late (13 weeks) time points after surgical orthotopic implantation, serum PTHrP was measured and primary and metastatic tumor burden was determined for each mouse by assessing GFP expression. By 5 weeks after surgical orthotopic implantation (early group), the mean serum PTHrP level was 33.3 pg/mL. In contrast, by 13 weeks after surgical orthotopic implantation (late group), the mean serum PTHrP level increased to 158.5 pg/mL. These differences were highly significant (p < 0.001, Student t test). Numerous metastatic lesions were readily visualized by GFP in the late group. Serum PTHrP levels measured by immunoassay correlated with primary pancreatic tumor weights and serum calcium levels (p <0.01). PTHrP levels were not detectable (<21 pg/mL) in any of the 10 control mice with no tumor. Western blotting of BxPC-3-GFP tumor lysates confirmed the presence of PTHrP. BxPC-3-GFP tumor tissue stained with antibody to PTHrP. These results indicate that PTHrP can serve as a tumor marker in animal models of pancreatic cancer and may be a useful tumor marker for clinical pancreatic adenocarcinoma.

Higher expression of K-ras is associated with parathyroid hormone-related protein-induced hypercalcaemia in renal cell carcinoma.

To determine whether the K-ras oncogene is associated with parathyroid hormone-related protein (PTHrP) production in renal cell carcinoma (RCC) and whether the serum value of PTHrP is related to the patients' survival. The serum levels of PTHrP and corrected serum calcium levels were analysed in 51 consecutive patients (29 men and 22 women, mean age 63.7 years, range 33-82) with newly diagnosed RCC. Matched pairs were analysed of the mRNA levels of K-ras and PTHrP in tumour and in corresponding non-tumour tissue originating from the same patient, using the polymerase chain reaction after reverse transcription. Seven patients had elevated serum PTHrP values at the diagnosis of RCC. The mRNA expression of K-ras and PTHrP were detected in both tumour and non-tumour tissues, with K-ras mRNA levels being higher in the former than the latter (P < 0.05), and correlated with tumour stage (P < 0.05). There were no differences in PTHrP mRNA levels between the tissues. Furthermore, the mRNA levels of K-ras and PTHrP in seven tumours from patients with high serum values of PTHrP were higher than in tumours from those with normal values (both P < 0.01). The expression of mRNAs of K-ras and PTHrP was positively correlated (r = 0.771, P < 0.001). In seven patients with high serum PTHrP values the mRNA levels of PTHrP correlated with serum values of PTHrP and calcium (r = 0.875, P < 0.01 and r = 0.762, P < 0.05, respectively). Kaplan-Meier plots of survival rate in patients with elevated or normal serum PTHrP showed that high serum PTHrP was associated with a shorter overall survival (P < 0.05). The Cox proportional hazards model showed that serum PTHrP was an independent predictor of overall survival (P < 0.05). These findings suggest that K-ras may be associated with PTHrP-induced hypercalcaemia and that PTHrP levels may reflect the aggressiveness of tumour cells through the K-ras oncogene in RCC.

Bone metastasis model with multiorgan dissemination of human small-cell lung cancer (SBC-5) cells in natural killer cell-depleted SCID mice.

Lung cancer is commonly associated with multiorgan metastasis, and bone is a frequent metastatic site for lung cancer. Nevertheless, no bone metastasis model of lung cancer with multiorgan dissemination is available, which could provide opportunity to study the molecular pathogenesis. We examined the abilities of eight human lung cancer cell lines injected intravenously into natural killer (NK) cell-depleted SCID mice to generate metastatic nodules in bone and multiple organs, and explored the correlation of the parathyroid hormone-related protein (PTHrP) with the bone metastasis. Although all the small-cell carcinoma cell lines (SBC-5, SBC-3, SBC-3/ADM, H69, H69/VP) formed metastatic nodules in multiple organs (liver, kidney, and lymph nodes), only SBC-5 cells reproducibly developed bone metastases. Squamous cell carcinoma (RERF-LC-AI) cells metastasized mainly into the liver and kidneys, whereas adenocarcinoma (PC-14, A549) mainly produced colonies in the lungs. As assessed by X-ray photography, the osteolytic bone metastases produced by SBC-5 cells were detected as early as on day 28, and all recipient mice developed bone metastasis by day 35. The expression of PTHrP in eight cell lines was directly correlated with the formation of bone metastasis. No correlation was observed between the formation of bone metastasis and the expression of other metastasis-related cytokines (IL-1, IL-6, IL-8, IL-10, IL-11, TNF-alpha, VEGF, M-CSF). Consistent with the formation of bone metastasis by SBC-5 cells, the levels of PTHrP and calcium in the mouse serum were increased in a time-dependent manner, suggesting that PTHrP produced by human lung cancer may play a crucial role in the formation of bone metastasis and hypercalcemia. These findings indicate that a bone metastasis model of SBC-5 cells may be useful for clarifying the molecular aspects of the metastatic processes in different organ microenvironments and the development of therapeutic modalities for lung cancer patients with bone metastases.

Technical and Clinical Validation of an Immunoradiometric Assay for Circulating Parathyroid Hormone-related Protein

Parathyroid hormone-related protein (PTHrP) plays a key role in hypercalcemia of malignancy (HM), particularly in humoral HM (HHM) (1)(2). Serum PTHrP is increased in 47–100% of HM patients (3)(4)(5)(6) and in almost all patients with HHM. In up to two-thirds of hypercalcemic patients with bone metastases, serum PTHrP is increased (5)(7). PTHrP assays may aid in the diagnosis of HHM (8). IRMAs that measure large N-terminal regions appear to be optimal for HM evaluation (9). With the first commercially available IRMA (Nichols Institute), PTHrP concentrations were found to be increased in 40 of 81 (49%) HM patients. Moreover, healthy subjects had detectable values up to 2.6 pmol/L (10), contrary to some reports (5)(8)(11). With an IRMA from Mitsubishi Petrochemical Co (12), PTHrP was increased in all 46 studied patients with hypercalcemia and solid tumors, and most healthy subjects had values <1 pmol/L. However, almost all patients had HHM, and the specificity toward normocalcemic cancer (C.NoCa) patients was not thoroughly investigated. We have evaluated a commercially available PTHrP IRMA. We particularly studied the assay specificity for HM patients compared with normocalcemic patients presenting an active cancer, with patients in complete remission from their cancer, and with patients suffering from osteopenia, osteoporosis, or chronic renal failure (CRF). The first control group included 94 patients (88 women and 6 men), median age 61 years (range, 26–80 years), referred to our bone clinic for a low bone mass or established osteoporosis. The patients were classified (13) as follows: 39 osteopenic (T score at the lumbar spine of −1.78 ± 0.09, mean ± SE); 29 osteoporotic (T score −3.16 ± 0.10); 26 established osteoporosis (low bone mass and presence of one or more fragility fractures). The second control group included …

Hypercalcemia Due to Parathyroid Hormone-Related Protein Produced by Primary Ovarian Clear Cell Adenocarcinoma: Case Report

Objective. Amongovarian carcinomas, clear cell adenocarcinoma is one of the most common histologic subtypes associated with hypercalcemia. However, the mechanisms of hypercalcemia in clear cell adenocarcinoma are still unclear. In the following case report, we tried to determine the etiology of hypercalcemia and also to demonstrate the management of hypercalcemia diagnosed preoperatively.Case. A 49-year-old woman was diagnosed as having a malignant ovarian tumor with hypercalcemia caused by elevated serum parathyroid hormone-related protein (PTHrP) prior to her primary surgery. Treatment with disodium incadronate promptly normalized the serum calcium level. An immunohistochemical study demonstrated PTHrP expression in the primary ovarian lesion, but not in the metastatic lesion. A Northern blot analysis of the cancer cells from the ovarian tumor confirmed the presence of PTHrP mRNA.Conclusion. Humoral hypercalcemia of malignancy in this case has been conclusively shown to be due to the production of PTHrP at the primary ovarian tumor, based on both immunohistochemical and molecular analyses.

Serum Parathyroid Hormone-Related Protein Levels and Response to Bisphosphonate Treatment in Hypercalcemia of Malignancy

Serum Parathyroid Hormone-Related Protein Levels and Response to Bisphosphonate Treatment in Hypercalcemia of Malignancy

Hypercalcaemia in melanoma patients associated with increased levels of parathyroid hormone-related protein.

We analysed serum levels of calcium and parathyroid hormone-related protein (PTH-rP) in 59 patients with melanoma by immunoradiometric assay, since only a few studies have been conducted on hypercalcaemia and serum levels of PTH-rP in patients with melanoma. Hypercalcaemia was found in seven of the 59 patients with melanoma. The serum level of PTH-rP was increased in three of the 59 patients and two of the three showed hypercalcaemia. All the patients with hypercalcaemia and/or an increased level of PTH-rP had stage IV melanoma. These findings suggest that hypercalcaemia is much more common than previously reported in patients with advanced stage melanoma and that an increased serum level of PTH-rP is one of the causative factors in hypercalcaemia in melanoma. Analysis of the serum PTH-rP level will contribute to the monitoring of the clinical course of patients with advanced stage melanoma.

Simultaneous elevation of serum parathyroid hormone(PTH) and parathyroid hormone-related protein(PTHrP) in a case of lung cancer with hypercalcemia

The parathyroid hormone related protein(PTHrP) is the most common causative peptide of humoral hypercalcemia of malignancy. In contrast, the serum level of parathyroid hormone(PTH) is low to undetectable in the majority of patients with malignancy associated hypercalcemia. Few cases exist in which the production and secretion of PTH by malignant nonparathyroid tumors have been authenticated. To our knowledge, there is very rare case in which a nonparathyroid tumor expressed simultaneously both the PTH and PTHrP. We report a case of squamous cell carcinoma of the lung with hypercalcemia which presented with simultaneous elevation of serum PTH and PTHrP. Severe hypercalcemia (serum calcium, 7.5mEq/L) was found in a 65-year-old man who had a squamous cell carcinoma of the lung without any body metastasis and detectable parathyroid abnormalities on isotope scintigraphy. The serum level of intact parathyroid hormone (PTH) concentration was markedly elevated as measured in two site radioimmunoreactive PTH assays (intact PTH 150pg/mL ; normal 9~55). The serum level of a PTHrP was also increased as measured in C-terminal region specific radioimmunoassay (PTHrP 99.1 pmol/L ; normal 13.8~55.3). There are no evidences of coincidental primary hyperparathyroidism in parathyroid MIBI scan and other imaging studies including neck ultrasonography and computed tomography. These results suggest that simultaneous elevation of serum PTH and PTHrP in this patient can be caused by production of both PTHrP and PTH in other nonparathyroid lesions such as squamous cell carcinoma.

Hypercalcemia in children with rhabdomyosarcoma.

Hypercalcemia complicating malignancy is a serious and frequent occurrence in adults but rare in children. The aim of this study was to determine the incidence, symptoms, outcome, and cause of hypercalcemia in children with rhabdomyosarcoma. Among 93 children with rhabdomyosarcoma, six with hypercalcemia were identified and their clinical course, pathologic findings, treatment, and outcome were evaluated. In addition, serum and intratumor parathyroid hormone-related protein (PTHrP) concentrations were measured to ascertain the potential of hypercalcemia. All six patients with hypercalcemia had bone metastasis, and four with severe hypercalcemia had multiple bone metastases. Serum PTHrP levels were moderately elevated. There were no significant trends detected based on age, gender, primary site, and pathologic type. All patients achieved transient resolution of hypercalcemia after treatment. However, none survived for a long period of time because their original tumor eventually recurred. Hypercalcemia is not an uncommon complication in patients with rhabdomyosarcoma. Bone absorption seems to be the predominant factor that induces the hypercalcemia in rhabdomyosarcoma. However, PTHrP may be a powerful stimulator of bone absorption, which contributes to the growth of bone metastasis.

Mechanisms of bone lesions in multiple myeloma and lymphoma

Bone lesions and hypercalcemia occur rarely in patients with hematologic malignancies, except those patients with multiple myeloma and adult T-cell leukemia/lymphoma (ATL) associated with the human T-cell leukemia/lymphoma virus-1 (HTLV-1) virus. The primary mechanism for bone destruction in patients with myeloma and lymphoma is increased osteoclastic bone resorption. In patients with multiple myeloma, new bone formation is also inhibited. Mediators including lymphotoxin, interleukin-1beta, parathyroid hormone related protein (PTHrP), and interleukin-6, produced by the myeloma cells or by marrow stromal cells in response to myeloma cells, have been implicated as osteoclast-activating factors (OAF) in multiple myeloma. However, most studies to identify OAF produced by myeloma cells have been inconclusive. To try to identify the OAF produced by myeloma cells, we developed an in vivo model of human myeloma bone disease using the ARH-77 myeloma cell line transplanted into severe combined immunodeficiency mice. We found that a novel cytokine(s) may be responsible for bone destruction. Interleukin-1 and PTHrP mediate bone destruction in patients with ATL. These factors can be detected in media conditioned by ATL cells or by lymphocytes infected with HTLV-1. Furthermore, serum PTHrP levels are increased in ATL patients. In patients with Hodgkin's disease or other types of non-Hodgkin's lymphoma, 1,25-(OH)2D3 or PTHrP is produced by the lymphoma cells and mediates bone destruction. Chemotherapy or resection of the lymphoma decreases 1,25-(OH)2D3 levels and hypercalcemia in these patients. Thus, OAF produced locally by the tumor or the marrow microenvironment play an important role in the bone destruction seen in patients with hematologic malignancies.

Parathyroid hormone and parathyroid hormone related protein assays in the investigation of hypercalcemic patients in hospital in a Chinese population.

There are many pathological causes and potential mechanisms for hypercalcemia. We measured intact parathyroid hormone (PTH) and parathyroid hormone related protein (PTHrP) in the hypercalcemic in-patients and attempted to evaluate the roles of PTH and PTHrP in hypercalcemia due to malignancy. We performed a prospective study of 178 patients with corrected serum calcium concentrations greater than 2.74 mmol/l in a hospital over a 3-year period. We measured calcium and albumin using a Hitachi 747 autoanalyzer, and we measured PTH and PTHrP by two-site immunoradiometric assays (IRMA). Hypercalcemia was attributed to malignancy alone in 93 patients (52.3%), primary hyperparathyroidism (HPT) alone in 28 patients (15.7%), uremia with hemodialysis in 23 patients (12.9%), unknown in 16 patients (9%), primary HPT coexisting with malignancy in 7 patients (3.9%) and other rare causes (6.2%). Plasma PTHrP levels were elevated in 71/93 (76.3%) patients with hypercalcemia due to malignancy, but the elevated PTHrP percentage differed for each kind of tumor. PTHrP levels were elevated in 100% of patients with squamous carcinomas (CA) in the lung, esophagus, skin, cholangiocarcinoma of liver, and breast CA. The positive bony metastatic rate was 44.1% (41/93). There was no correlation between high PTHrP and bony metastasis. There was a good correlation between the corrected serum calcium and PTHrP levels (r = 0.476, p < 0.001), but no correlation between survival time and serum calcium level or PTHrP level. There was no significant difference in life expectancy after cancer diagnosis between the high PTHrP group and normal PTHrP group, and there was no significant difference in life expectancy after the first occurrence of hypercalcemia between the two groups. Measurement of both PTH and PTHrP levels led to a change in the initial diagnosis in 7 patients. In routine practice, measurement of serum PTH alone is not enough. This study suggests that the appropriate combination of PTH and PTHrP assays results in a more accurate diagnosis of the hypercalcemic causes. In addition, especially high PTHrP levels should be screened for malignancy. However, the prognosis in cancer patients after hypercalcemia with high PTHrP group, as compared to those with the normal PTHrP group is not significantly different.

In situ detection of parathyroid hormone-related protein in ovarian clear cell carcinoma

A case of ovarian clear cell carcinoma associated with hypercalcemia is reported. A 67-year-old woman developed the lung metastasis 8 months after primary surgery. The patient manifested symptoms of humoral hypercalcemia of malignancy (HHM) during the last 3 months of her clinical course. Serum and urinary C-terminus parathyroid hormone-related protein (PTHrP) levels were remarkably high. No increase in interleukin (IL) 1β, tumor necrosis factor (TNF) α, vitamin D 3 metabolites or intact PTH was detected. Pamidronate disodium treatment was transiently suppressed her serum calcium level. The patient died despite seven courses of chemotherapy. Autopsy showed multiorgan metastases and accelerated osteoclastic bone resorption; skeletal metastasis was not detected. Immunohistochemical analysis clearly showed the localization of PTHrP at both the primary and metastatic sites. The transcripts of PTHrP at pulmonary metastatic sites were revealed by in situ hybridization and the reverse transcription polymerase chain reaction (RT-PCR) method. PTHrP was the causative factor for HHM in this case. It is therefore suggested that hypercalcemia may have occurred after PTHrP produc tion had overcome the homeostatic level during the terminal stage, although PTHrP production continued irrespective of the patient's serum calcium level.

Tumor-induced hypercalcemia and parathyroid hormone-related protein in lung carcinoma.

Although lung carcinoma is the most common cause of tumor-induced hypercalcemia (TIH), the precise incidence of TIH remains obscure. Furthermore, the role of parathyroid hormone-related protein (PTHrP) has not been clearly elucidated. This study included 690 consecutive patients who were newly diagnosed as having lung carcinoma between 1989 and 1994 (379 adenocarcinomas, 207 squamous cell carcinomas, 75 small cell carcinomas, and 29 large cell carcinomas). All patients were treated for lung carcinoma and were also periodically monitored for their serum level of calcium (Ca). Hypercalcemia was defined as a serum Ca concentration higher than 11 mg/dL. The serum levels of PTHrP (109-141) were measured by a C-terminal-region-specific radioimmunoassay. TIH was observed in 17 of 690 patients (2.5%). All 17 patients demonstrated an advanced stage of lung carcinoma (Stage III or IV), 10 squamous cell carcinomas, 5 adenocarcinomas, 1 small cell carcinoma, and 1 large cell carcinoma. In 15 patients, the serum level of C-PTHrP (109-141) was substantially high, ranging from 99 pmol/L to 890 pmol/L (normal range, 21-50.7 pmol/L). There was no significant difference in the serum PTHrP level between patients with or without bone metastasis. The reduction of tumor burden decreased both the serum level of PTHrP and that of Ca in parallel. The median survival time after diagnosis of TIH was only 27 days. TIH in lung carcinoma was most likely attributable to PTHrP, and its occurrence appears to be an ominous prognostic sign.

Circulating parathyroid hormone-related protein (109-141) in malignancy-associated hypercalcemia.

For differential diagnosis between hypercalcemia-induced bone metastasis and humoral hypercalcemia of malignancy (HHM), serum parathyroid hormone-related protein (PTHrP) concentrations were measured in normal subjects and patients with malignancy-associated hypercalcemia according to the presence or absence of bone metastasis, using a new sensitive PTHrP(109-141) radioimmunoassay system. The serum PTHrP(109-141) levels in all of 14 patients without bone metastasis were significantly higher than those in normal subjects. However, in four patients with hypercalcemia associated with bone metastasis the levels were nearly the same as those in normal subjects. The time course in two hypercalcemic patients with esophageal carcinoma revealed that serum PTHrP(109-141) levels were elevated before hypercalcemia developed and that changes in PTHrP(109-141) and corrected serum calcium levels were significantly correlated. These findings suggest that determination of serum PTHrP(109-141) may be clinically important not only for differential diagnosis of HHM but also as a useful predictive marker of hypercalcemia.

Acute pancreatitis induced by hypercalcaemia associated with adult T‐cell leukaemia: A case report

A 44 year old Japanese woman with adult T-cell leukaemia (ATL) was admitted to Kyushu University hospital to receive a course of alpha-interferon treatment. She experienced a sudden onset of hypercalcaemia and epigastric pain associated with an increase in the level of pancreatic enzymes. Her serum parathyroid hormone related protein level was above normal although her high sensitive PTH level was within the normal range. Ultrasonography and computed tomography (CT) of the abdomen showed enlargement of the pancreas with indistinct margins and massive accumulation of extrapancreatic fluid. Cullen's sign was observed. A few days after the onset of acute pancreatitis, the serum amylase level increased to 3400 IU/L, and the serum calcium level fell to 4.2 mg/dL from 13.3 mg/dl. Her fasting blood glucose level increased to 242 mg/dL. Although the first episode of pancreatitis appeared to respond to treatment, she experienced a second episode of pancreatitis accompanied by an elevation of the serum calcium level. These findings suggest that acute pancreatitis was caused by hypercalcaemia associated with ATL.

Clinical and biological significance of serum tumor markers in adult T-cell leukemia.

As the clinical manifestations of adult T-cell leukemia (ATL) can be quite diverse, useful indicators for the therapy and prognosis are required for the disease. In this review, the clinical and biological significance of serum tumor markers at diagnosis in ATL patients is described. Serum lactic dehydrogenase (S-LDH), serum thymidine kinase (S-TK) and serum parathyroid hormone-related protein (S-PTHrP) at diagnosis of ATL showed a correlation with among leukocyte count, absolute number of abnormal lymphocytes with polymorphic nuclei, platelet count, serum calcium and the length of survival after the initial diagnosis. Serum beta 2-microglobulin (S-beta 2M) correlated with age, platelet count and survival. A statistical correlation existed between these four serum tumor markers. Other serum tumor markers such as immunosuppressive acidic protein (S-IAP), ferritin (S-Ft) and tissue polypeptide antigen (S-TPA) showed no correlation with clinical and histological data in ATL patients.