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1.
Hypercalcemia induced with the plasma levels of parathyroid hormone-related peptide in multiple myeloma 总被引:1,自引:0,他引:1
Shionoiri A Horiuchi T Onouchi T Tsutsumi H Ohta M Hosoi T Ito H Orimo H 《Internal medicine (Tokyo, Japan)》2000,39(10):810-813
A 69-year-old man visited our department of neurology with symptoms of paresthesia on the lower extremities and lumbago. Biochemical examination of serum samples showed hypercalcemia (serum concentration 15.6 mg/dl). The levels of intact parathyroid hormone (i-PTH) and 1,25-dihydroxyvitamin D were suppressed, whereas parathyroid hormone-related peptide (PTHrP) was elevated up to 5.4 pM (normal range: below 0.6 pM). Additionally, bone survey revealed a punched-out lesion in radiological examinations of the skull. Bone marrow aspiration demonstrated many atypical plasma cells suggesting multiple myeloma. Nephrogenous cyclic adenosine monophosphate (cAMP), urinary deoxypyridinoline, plasma interleukin 6 (IL-6) and transforming growth factor beta (TGF beta) concentrations were elevated, whereas % of renal tubular reabsorption of phosphate (%TRP) was decreased. The immunohistochemical results demonstrated the expression of PTHrP in atypical plasma cells. These data indicated that hypercalcemia complicating multiple myeloma causes an elevation of renal calcium reabsorption and an increase of bone resorption mediated by PTHrP action. 相似文献
2.
T J Rosol L A Nagode C G Couto A S Hammer D J Chew J L Peterson R D Ayl C L Steinmeyer C C Capen 《Endocrinology》1992,131(3):1157-1164
Circulating N-terminal PTH-related protein (PTHrP), N-terminal PTH, and 1,25-dihydroxyvitamin D [1,25-(OH)2D] concentrations were measured in normal dogs and dogs with cancer-associated hypercalcemia (CAH), parathyroid adenomas, and miscellaneous tumors. PTHrP was undetectable (less than 1.8 pM) in normal dogs and increased in dogs with CAH due to adenocarcinomas derived from apocrine glands of the anal sac (44.9 +/- 27 pM), lymphoma (8.3 +/- 4.4 pM), and miscellaneous carcinomas (13.3 +/- 11.4 pM). The PTHrP concentration decreased in dogs with lymphoma and anal sac adenocarcinomas after successful treatment of CAH. The PTHrP concentration had a significant linear correlation with total serum calcium in dogs with anal sac adenocarcinomas and hypercalcemia, but not in dogs with lymphoma and hypercalcemia. Serum N-terminal PTH concentrations were usually in the normal range (12-34 pg/ml) for all groups of dogs except dogs with parathyroid adenomas (83 +/- 38 pg/ml). The serum PTH concentration increased after successful treatment of CAH. Serum 1,25-(OH)2D concentrations were decreased, normal, or increased in dogs with CAH, and 1,25-(OH)2D levels decreased after treatment of CAH. In summary, circulating concentrations of PTHrP are consistently increased in dogs with CAH, and PTHrP appears to play an important role in the induction of hypercalcemia. 相似文献
3.
Takasaki H Kanamori H Takabayashi M Yamaji S Koharazawa H Taguchi J Fujimaki K Ishigatsubo Y 《American journal of hematology》2006,81(6):439-442
We report a rare case of a patient with non-Hodgkin's lymphoma who developed multiple bone lesions and hypercalcemia. A 50-year-old woman complained of drowsiness and multiple bone pain on admission. Radiographic examination revealed multiple bone fractures and osteolytic lesions. She was diagnosed with diffuse large B cell lymphoma by biopsy of an inguinal lymph node. Elevation of parathyroid hormone-related protein (PTHrP) and hypercalcemia were confirmed pretreatment, and those serum levels decreased during chemotherapy for lymphoma. However, the disease was resistant to chemotherapy combined with rituximab. These findings suggest that hypercalcemia is associated with PTHrP and the prognosis of patients with bone lymphoma in advanced stage is poor, although it is thought to be a relatively favorable prognosis in localized primary lymphoma of bone. 相似文献
4.
Shimizu H Monden T Tomotsune T Nakatani Y Domeki N Matsumura M Jojima T Kawagoe Y Kasai K 《Internal medicine (Tokyo, Japan)》2011,50(24):2993-2996
A 62-year-old woman was admitted with dry mouth, general fatigue, and severe back pain. Biochemistry examination showed extreme hypercalcemia (21.2 mg/dL). Bone marrow examination was negative, but needle biopsy of a metastatic lung tumor revealed abnormal plasma cells; thus, multiple myeloma stage III-A was finally diagnosed. Serum concentrations of both parathyroid hormone-related peptide (PTHrP) and macrophage inflammatory protein-1α (MIP-1α) were markedly elevated (PTHrP 7.2 pmol/L, normal <1.1 pmol/L; MIP-1α 84.9 pg/mL, normal <46.9 pg/mL). Her myeloma appeared to have simultaneously caused two mechanisms producing hypercalcemia: humoral hypercalcemia of malignancy (HHM) by PTHrP and local osteolytic hypercalcemia (LOH) by MIP-1α. Therefore, the combination of two calcium-modulating abnormalities likely aggravated her hypercalcemia. 相似文献
5.
Hiroyuki A. Watanabe Hiroshi Matsushita Hideo Matsui Tsutomu Komatsu Susumu Taguchi Hiroshi Sata Nagahisa Amano 《Journal of gastroenterology》1999,34(4):510-515
We report two patients with esophageal carcinoma with high levels of serum parathyroid hormone-related protein (PTHrP). Patient
1 was a 66-year-old man in whom the serum calcium level was also high, and patient 2 was an 81-year-old woman. The serum PTHrP
level was 411 pM (normal range, 13.8–55.3 pM) in patient 1 and 94.5 pM in patient 2 (in whom the serum granulocyte colony-stimulating
factor level was also high). We demonstrated PTHrP immunohistologically in esophageal carcinoma cells in both patients. After
admission, patient 1 died of pneumonia on the 17th day of hospitalization (the 48th day after he had had an episode of frequent
hiccuping) and patient 2 died of acute circulatory failure on the 12th day of hospitalization (the 25th day after she had
vomited after a meal). Neither of these patients died of cancer. Pneumonia in patient 1 was believed to be due to weakened
body defenses, while the acute circulatory failure in patient 2 was due to emaciation. Since esophageal carcinoma with humoral
hypercalcemia of malignancy and leukocytosis is characterized by rapid progression and metastasis, early diagnosis and treatment
are mandatory.
Received: December 10, 1998 / Accepted: February 26, 1999 相似文献
6.
Yoshitaka Imoto Naoki Muguruma Tetsuo Kimura Masako Kaji Hiroshi Miyamoto Seisuke Okamura Susumu Ito Masahiko Nakasono Mitsuyoshi Hirokawa Toshiaki Sano 《Nihon Shokakibyo Gakkai zasshi》2007,104(3):401-406
Humoral hypercalcemia of malignancy (HHM) in neoplastic syndrome has been most commonly reported in squamous cell carcinoma. Gallbladder carcinoma with HHM is uncommon. In this report, we describe a male case of gallbladder carcinoma with marked hypercalcemia and a high level of serum parathyroid hormone-related peptide (PTHrP). An immunohistochemical examination using PTHrP was also positive. 相似文献
7.
Hayashi T Mizuki A Yamaguchi T Hasegawa T Kunihiro T Tsukada N Matsuoka K Orikasa H Yamazaki K 《Internal medicine (Tokyo, Japan)》2001,40(7):631-634
A 55-year-old man was admitted to our hospital with fever and vomiting. Abdominal computed tomography (CT) revealed multiple low density masses in the liver. A diagnosis of primary adenosquamous carcinoma of the liver was confirmed by histological examination of a necropsy specimen. The present case showed leukocytosis and hypercalcemia with high levels of serum granulocyte-colony-stimulating factor (G-CSF) and parathyroid hormone related protein (PTHrP). Recent studies have shown that G-CSF and PTHrP are responsible for the paraneoplastic syndromes with leukocytosis and hypercalcemia. The tumor cells demonstrated positive cytoplasmic immunohistochemistry staining with anti-G-CSF and anti-PTHrP antibodies. This result suggested that the tumor produced G-CSF and PTHrP. 相似文献
8.
Miyoshi N Tanaka H Ito T Katayama Y Niimi H Hyodo H Kimura A 《International journal of hematology》2005,82(4):333-337
The case of a 72-year-old woman with chronic myelogenous leukemia in blast phase (BP) with hypercalcemia is reported. Bone x-ray examination revealed multiple osteolytic lesions throughout the body. The serum level of parathyroid hormone-related protein (PTHrP) was elevated, and PTHrP messenger RNA (mRNA) was detectable in the peripheral blood mononuclear cells (PBMNC) at BP but was not detectable at chronic phase (CP).Treatment with conventional chemotherapy did not completely control either serum calcium level or serum PTHrP level. Treatment with imatinib mesylate (imatinib) alone rapidly normalized these parameters in parallel with a decrease in the number of blast cells. The treatment also maintained the patient in good condition for approximately 3 months, even though the number of blast cells, serum calcium level, serum PTHrP level, and PTHrP mRNA level increased at the terminal stage. Mutations of the p53, K-Ras, and BCR-ABL genes in PBMNC at BP were absent. A noteworthy feature in this patient was that PBMNC at BP but not at CP showed high Lyn mRNA expression. Taken together the findings showed that production of PTHrP by blast cells was favorably controlled by imatinib therapy alone. Imatinib may prolong survival time at BP even though the patients have the complication of PTHrP-mediated hypercalcemia. 相似文献
9.
Couri CE Foss NT Dos Santos CS de Paula FJ 《The American journal of the medical sciences》2004,328(6):357-359
Despite the high prevalence of leprosy in undeveloped countries, hypercalcemia secondary to leprosy is rare. One of most important mechanisms responsible for this disorder seems to be high serum concentrations of 1,25-dihydroxyvitamin D produced extrarenally by the granulomatous tissue. Serum levels of parathyroid hormone-related protein (PTHrP) have never been analyzed in this disorder. We report here a case of hypercalcemia in a patient with leprosy. Serum levels of 1,25-dihydroxyvitamin D were normal in spite of low levels of 25-dihydroxyvitamin D and acute renal failure. Suppressed serum levels of parathyroid hormone and PTHrP were also remarkable. In this case, PTHrP seems not to play an important role in the pathogenesis of hypercalcemia. Our data indicate that this disorder may be due, at least in part, to abnormal calcitriol overproduction by granulomatous tissue. Further investigations of the prevalence and pathogenesis of this type of hypercalcemia are needed. 相似文献
10.
Hypercalcemia associated with parathyroid hormone-related protein produced by B-cell type primary malignant lymphoma of the kidney 总被引:1,自引:0,他引:1
A patient with primary non-Hodgkin's (B-cell type) lymphoma of the kidney developed hypercalcemia at the terminal stage of
the disease. Although the plasma parathyroid hormone level was low, urinary cyclic AMP excretion was elevated. Serum osteocalcin
(BGP) was suppressed and the plasma level of 1,25(OH)2D was within the normal range. Serum concentrations of PTH-related protein (PTHrP)-like immunoreactivity (PRP-LI) were elevated,
and the tissue concentration of PRP-LI in the postmortem lymph node showed high level along with elevated serum PRP-LI, furthermore
the production of PTHrP by the tumor was demonstrated by immunohistochemistry and Northern blotting analysis. These findings
indicate that the hypercalcemia of the patient was caused by the PTHrP-producing B-cell lymphoma. Hypercalcemia was restored
to normocalcemia by bisphosphonate treatment. Our case will add further information on humoral hypercalcemia in B-cell lymphoma,
which rarely has been demonstrated to produce PTHrP.
Received: 17 July 1997 / Accepted: 2 February 1998 相似文献
11.
Kounami S Yoshiyama M Nakayama K Hiramatsu C Aoyagi N Yoshikawa N 《Acta haematologica》2004,112(3):160-163
Among the hematological malignancies, hypercalcemia has often been reported in lymphoid malignancies such as multiple myeloma and adult T cell leukemia/lymphoma, but it has only rarely been described in acute nonlymphocytic leukemia. We describe here a 14-month-old girl with acute monocytic leukemia complicated by severe hypercalcemia (4.6 mmol/l) at presentation. A bone survey showed generalized bone resorption, but no localized osteolytic lesions. A search for the etiology of the hypercalcemia revealed that the serum levels of parathyroid hormone-related protein (PTHrP) and also proinflammatory cytokines with stimulatory effects on osteolytic bone resorption - TNF-alpha, IL-6 and M-CSF - were elevated. The patient achieved complete remission with induction chemotherapy, and the levels of PTHrP and the cytokines became normalized. In this case, PTHrP and cytokines might have acted cooperatively to exacerbate bone resorption, resulting in severe hypercalcemia. 相似文献
12.
Uchimura K Mokuno T Nagasaka A Hayakawa N Kato T Yamazaki N Kobayashi T Nagata M Kotake M Itoh M Tsujimura T Iwase K 《Metabolism: clinical and experimental》2002,51(7):871-875
In general, many cases of malignancy-associated hypercalcemia are due to HHM. In patients with humoral hypercalcemia of malignancy (HHM), it has been reported that plasma parathyroid hormone-related protein (PTHrP) and cyclic adenosine monophosphate (cAMP) levels were elevated, while plasma PTH and active vitamin D(3) levels were suppressed. Our patient showed hypercalcemia with a concurrent increase in plasma and tumor tissue PTHrP and PTH concentrations and also high cAMP and low 1-25(OH)(2)VD(3) levels in the plasma. These data suggest that the hypercalcemia exhibited by our patient was consistent with HHM due to lung cancer and its liver metastasis. Moreover, diagnostic imaging and autopsy findings showed no appreciable lesions of the parathyroid gland. In addition, histopathologic examination of the primary and metastatic tumors revealed the existence of PTH immunohistochemically stained with anti-PTH antibodies, suggesting an ectopic-PTH-producing lung tumor. From these data, our patient was diagnosed with a rare case of lung cancer, which produced both ectopic PTH and PTHrP. 相似文献
13.
Kakihana K Mizuchi D Yamaguchi M Sakashita C Fukuda T Yamamoto K Miki T Tohda S Koyama T Murakami N Miura O 《[Rinshō ketsueki] The Japanese journal of clinical hematology》2002,43(2):102-106
A 45-year-old man with chronic myelogenous leukemia (CML) in the accelerated phase was admitted to our hospital because of lower back pain and hypercalcemia. On admission, he was confused and found to have massive splenomegaly. The hypercalcemia and splenomegaly improved significantly after administration of incadronate, hydroxyurea, vincristine and prednisolone. Splenomegaly recurred after cessation of the chemotherapy, and examination of the peripheral blood showed 31% blasts, positive for both CD13 and CD33, on which basis myeloid blastic transformation was diagnosed. Vindesine, cytarabine and prednisolone were administered, and the splenomegaly improved again. On admission, when the patient's serum calcium level was 16.0 mg/dl, his serum parathyroid hormone-related protein (PTHrP) level was elevated to 118.3 pmol/l. Furthermore, RT-PCR analysis revealed that the patient's CML cells expressed PTHrP mRNA, and a high level of PTHrP was detected in the supernatant of cultured mononuclear cells derived from the patient's peripheral blood. These findings indicated that the hypercalcemia was due to production of PTHrP by the leukemic cells. Several cases of PTHrP. mediated hypercalcemia associated with CML have been reported previously, and are reviewed here. 相似文献
14.
J D Zajac J Callaghan C Eldridge H Diefenbach-Jagger L J Suva P Hudson J M Moseley V P Michelangeli G Pasquini 《Molecular and cellular endocrinology》1989,67(1):107-112
Parathyroid hormone-related protein (PTHrP), the peptide associated with humoral hypercalcemia of malignancy, has been identified in fetal and adult parathyroid glands. We here report a sub-clone of a rat parathyroid cell line which secretes a single peptide species corresponding in size to PTHrP(1-84). Biological activity of the secretion product was blocked by a specific antiserum against PTHrP, but not by parathyroid hormone (PTH) antiserum. Secretion of PTHrP by these cells was regulated by extracellular calcium in the physiological range. A single messenger RNA species for PTHrP was identified, though PTH mRNA could not be shown in these cells. Hybrid CAT genes containing 700-1000 bp of 5'-flanking DNA from the human PTH or PTHrP genes were transfected into these cells, and the PTHrP gene was expressed at 10-fold higher levels than the PTH gene. These cells thus provide a valuable model system for investigation expression of PTHrP in a non-transformed cell line. 相似文献
15.
Tzu-Chen Yen Shinn-Jang Hwang Ching-Chen Wang Shou-Dong Lee Shin-Hwa Yen 《Liver international》1993,13(6):311-315
ABSTRACT— A two-site immunoradiometric assay (IRMA) of parathyroid hormone-related protein (PTHrP) was employed to react with circulating concentrations of PTHrP in 14 patients with hepatocellular carcinoma (HCC) and hypercalcemia (> 10.6 mg/dl). Eleven of them had unresectable lesions and three received transcatheter arterial chemo-embolization (TACE) treatment. Patients had no evidence of bony metastases and only one had evidence of a parathyroid lesion (by bone scan and serum parathyroid hormone level, respectively). The urinary cAMP level was increased in all patients, but the serum 1,25-dihydroxyvitamin D and plasma cAMP levels varied. Twelve patients had elevated alpha-fetoprotein (AFP) (> 400 ng/ml) and two of them had mildly elevated AFP levels (11 and 147 ng/ml). Their PTHrP concentrations were elevated (7.1 to 33.2 pmol/l), compared with normal levels obtained in our laboratory (< 3.5 pmol/l). A significant decrease in plasma PTHrP (from 27.4 to 5.2 pmol/1), serum calcium concentrations (from 16.3 to 9.4 mg/dl) and AFP levels (from 64 787 to 3129 ng/ml) was observed on the day following TACE treatment. These results, by using an improved technique, extend the findings that hypercalcemia in patients with HCC is associated with increased renal reabsorption of calcium and increased bone resorption of PTHrP generated by HCC. 相似文献
16.
We report a case of a 39-year-old female with active systemic lupus erythematosus who complained of lethargy and weakness with a moderate renal impairment. Hypercalcemia was confirmed by laboratory examination. Her X-ray revealed significant ectopic calcinosis in subcutaneous tissue of bilateral hands, and Tc-99m methylene diphosphonate bone scan revealed a remarkably intense uptake of bilateral lungs. She had no evidence suggestive of other diseases related to hypercalcemia such as hyperparathyroidism and malignancy. She had abnormally high serum parathyroid hormone-related protein (PTHrP) which fell to normal after treatment. Glucocorticoid, cyclophosphamide plus calcitonin and etidronate were administered and the patient improved greatly. Literature review demonstrated that lupus-related hypercalcemia with ectopic calcinosis is a rare complication and increased PTHrP is probably one of the main mechanisms. Lung uptake in bone scan may be a special and reliable clue suggestive of hypercalcemia. 相似文献
17.
Ping Chen Bingzong Li Wenzhuo Zhuang Haiwen Huang Hong Zhang Jinxiang Fu 《International journal of hematology》2010,91(4):716-722
We encountered a 58-year-old female patient who developed hypercalcemia and multiple bone lesions. She complained of lumbodorsal
pain, nausea and vomiting on admission. Radiographic examination revealed multiple osteolytic lesions. She was diagnosed diffuse
large B cell lymphoma (BLBCL) by bone marrow examination and biopsy of cervical lymph node. She underwent eight cycles of
chemotherapy and is now in the stable stage. Osteogenic potential of mesenchymal stem cells from bone marrow was found to
be correlated with the expression of Dickkopf1 (DKK-1) in the bone marrow plasma and lymphoma cells before and after treatment.
PTH-related protein (PTHrP) expression was detectable in the lymphoma cells and was elevated in the serum. The receptor activator
of nuclear factor κB ligand expression was found to be elevated in the bone marrow plasma and mesenchymal stem cells. These
findings suggest that factors affecting the differentiation of both osteoblasts and osteoclasts involved in the pathogenesis
of hypercalcemia and bone lesions of lymphoma. This was similar to that of multiple myeloma in which bone lesions and hypercalcemia
are frequently observed. 相似文献
18.
Yamada S Sanefuji H Morimoto H Harada Y Mine S Morimoto I Eto S 《Journal of gastroenterology and hepatology》2000,15(12):1442-1446
Humoral hypercalcemia caused by parathyroid hormone-related peptide (PTHrP), associated with cholangiocellular carcinoma (CCC), has rarely been documented. There have been no reports of CCC associated with extensive calcification of the tumor with psammoma body formation. A 66-year-old man was admitted with a large calcified tumor in the liver detected on an abdominal X-ray. An ultrasound-guided fine needle biopsy specimen of the liver tumor showed evidence of adenocarcinoma. He had hypercalcemia with an elevated PTHrP level. The patient died because of disseminated intravascular coagulation and progressive hepatic failure. A postmortem examination revealed a large poorly differentiated CCC in the liver. Immunohistochemical examination showed the presence of PTHrP-positive tumor cells. The calcified lesion consisted of a number of accumulated psammoma bodies. We present a case of PTHrP producing CCC with a marked psammoma formation. 相似文献
19.
Chinen Y Nakao M Sugitani-Yamamoto M Kiyota M Horiike S Kuroda J Taniwaki M 《International journal of hematology》2011,94(6):567-570
Intravascular B-cell lymphoma (IVLBCL) is a rare subtype of extranodal diffuse large B-cell lymphoma, which is characterized
by the growth of lymphoma cells within blood vessel lumina without nodular lesions, and which predominantly affects elderly
patients. IVLBCL is characterized by B-symptoms and a variety of systemic symptoms due to focal obstruction of blood flow,
but may be difficult to diagnose due to its peculiar intravascular localization and the lack of nodular lesions. While hypercalcemia
is one of the complications of various types of cancerous diseases, it has rarely been reported as the first presentation
of IVLBCL. In this report, we present the case of a 71-year-old male with IVLBCL who showed hypercalcemia accompanied by elevation
of serum parathyroid hormone-related protein (PTH-rP) as the initial presentation. Interestingly, immunohistochemical staining
revealed that the intravascular lymphoma cells expressed high levels of PTHrP. Six courses of immunochemotherapy, consisting
of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP), and two courses of high-dose methotrexate
induced complete remission (CR) and retained CR for 4 months. We also reviewed other IVBCL cases in which hypercalcemia was
the initial presentation. We suggest that IVLBCL, although rare, should be considered as a possible causative in hypercalcemia
of unknown underlying disease. 相似文献
20.
目的:探讨骨源性非霍奇金淋巴瘤(NHL)(弥漫型大B细胞性)伴继发性甲状旁腺机能亢进的诊断及机制。方法:对1例全身骨痛伴昏迷患者进行了骨髓图、骨髓病理及免疫组织化学、血液生化和CT检查,并复习文献就其诊治问题进行讨论。结果:CT显示多部位骨质破坏,血钙及甲状旁腺激素水平显著升高,骨髓病理及免疫组织化学检查证实为骨源性NHL(弥漫型大B细胞性),最终诊断为骨源性NHL(弥漫型大B细胞性)伴继发性甲状旁腺机能亢进。结论:骨源性NHL的诊断有赖于病理组织学、免疫学和细胞遗传学检查以及CT及核素扫描。淋巴瘤细胞分泌甲状旁腺激素相关蛋白或相关多肽(PTHrP),细胞因子与PTHrP的释放及溶骨损害是引起高钙血症的原因。 相似文献