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Query: UMLS:C0020437 (hypercalcemia)
 10,293 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A variety of tumors and nontumorous lesions were used to illustrate some of the biologic, clinical, and pathologic aspects of inappropriate or ectopic endocrine and metabolic syndromes that have musculoskeletal repercussions. It is clear, both from the discussion and case material, that many mechanisms of ectopic endocrine syndromes have yet to be clarified. Elaborate techniques are available for hormonal estimations, but their routine use is prohibitively expensive and relatively unrewarding. Cells of a given lesion may be functionally heterogeneous or may fail to elaborate active products in substantial amounts. Different cells may produce similar peptides, while the same cells can produce more than one. Despite these difficulties, recognition of ectopic endocrine syndromes remains crucial to diagnosis and patient management, and thus corroboration or correlation must often rest on a cruder basis. In fact, the clinical significance of basic laboratory data, e.g., PTH elevation, may vary, as PTH may be immunoreactive but biologically inactive. As another example, hypercalcemia associated with myeloma may be variously related to coexistent hyperparathyroidism, renal disease, dehydration, or humoral osteolysis. Therefore, roentgenographic evidence of bone destruction or skeletal stigmata of hyperparathyroidism imbues laboratory data with greater significance. Paraneoplastic syndromes are of particular concern to the radiologist, as multiple systemic manifestations, occurring either synchronously or metachronously, may suggest the presence of an underlying or unifying lesion or even of a specific type of neoplasm. They may precede detection of neoplasms by months to years and can develop at any time during their course. Paraneoplastic syndromes may, furthermore, parallel the course of a lesion and be used as indicators of remission or recurrence. Conversely, those unassociated with overt symptoms possess endocrine markers that can reinforce sometimes silent skeletal stigmata. Familiarity with representative secretory products influencing the musculoskeletal system per se may often clarify seemingly innocuous and sometimes asymptomatic skeletal findings. Alert imagers may, therefore, detect, infer, or suspect particular syndromes when they present in a specific sequence or mosaic. Conversely, when apprised of their existence, imagers should know where their related effects may be sought or anticipated. Such relationships, sometimes serendipitously discovered, may be valuable assets in clinical diagnosis and patient management in both suspected and unsuspected cases.
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PMID:Skeletal manifestations of ectopic or inappropriate endocrine and metabolic syndromes. 198 23

Paraneoplastic hypercalcemia associated with adenosquamous carcinoma of the endometrium is described. This is the first reported case of a gynecologic cancer in which the paraneoplastic syndrome has been conclusively shown by immunohistochemical analysis to be due to ectopic parathormone.
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PMID:Paraneoplastic hypercalcemia associated with adenosquamous carcinoma of the endometrium. 198 23

Hypercalcemia and leukocytosis may occur in conjunction as paraneoplastic syndromes associated with malignant disease. Here we describe a human squamous cell carcinoma of the maxilla that was associated with hypercalcemia and leukocytosis, and also cachexia. The primary tumor was surgically removed and established in permanent cell culture. When either primary tumors or cultured tumor cells were inoculated into nude mice, the nude mice developed the same paraneoplastic syndromes as those which occurred in the patient from whom the tumor was originally derived. The plasma calcium was increased two and one-half-fold and the WBC count 30-fold, and the body weight was decreased by 45% in tumor-bearing animals. Each of these paraneoplastic syndromes was alleviated by surgical excision of the tumor, indicating that the paraneoplastic syndromes were due to a factor or factors produced by the primary tumor. The development of each of these paraneoplastic syndromes in nude mice correlated positively with the other two syndromes. We examined the organs of tumor-bearing mice and found striking histopathologic abnormalities in the bones, spleen, and liver, but no infiltration with tumor cells. The bones showed marked evidence of osteoclastic bone resorption. This model of a human tumor associated with the hypercalcemia-leukocytosis paraneoplastic syndrome, together with cachexia, should make it possible to determine the mechanisms responsible for these paraneoplastic syndromes and their relationship to each other.
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PMID:Occurrence of hypercalcemia and leukocytosis with cachexia in a human squamous cell carcinoma of the maxilla in athymic nude mice: a novel experimental model of three concomitant paraneoplastic syndromes. 199 18

Hypercalcemia is the most frequent paraneoplastic syndrome observed in cancer patients. This morbidity can be divided into two categories: one is hypercalcemia induced by severe bone metastases; the other the elaboration of hypercalcemic factors by solid tumors, termed humoral hypercalcemia of malignancy (HHM). With regard to humoral factors responsible for HHM, a protein with parathyroid hormone (PTH)-like activity, designated PTH-related protein (PTHrP), was isolated from a cancer cell line established from a hypercalcemic patient's lung cancer tissue, and the structure of PTHrP mRNA was identified. Since the biological activity of PTHrP explained most of the clinical and laboratory findings of HHM patients and recent clinical studies indicated the very close relationship between the development of HHM and the production of PTHrP by tumor, PTHrP is now regarded to be the primary candidate for the actual factor responsible for HHM.
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PMID:[Malignancy-associated hypercalcemia]. 200 37

The structure of a novel protein, parathyroid hormone-related protein (PTHrP), secreted by human tumors associated with hypercalcemia has recently been determined. Administration of a synthetic fragment of this protein in vivo reproduces features of the clinical paraneoplastic syndrome of humoral hypercalcemia of malignancy and produces biologic responses closely similar to those obtained with parathyroid hormone (PTH). A PTH antagonist designed to reversibly occupy PTH receptors inhibited major actions of the tumor peptide in vivo, including phosphaturia, urinary cAMP excretion, and increased serum ionized calcium. These studies indicate that PTHrP and PTH mediate their bioactivities through shared receptors in vivo and establish a potential specific mechanism-based approach utilizing PTH antagonists for the therapy of tumor-associated hypercalcemia.
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PMID:The synthetic human parathyroid hormone-related protein is inhibited by a parathyroid hormone antagonist in rats in vivo. 216 20

We have demonstrated that T3M-1 cells and T3M-5 cells, derived from squamous carcinomas of patients with leukocytosis and hypercalcemia, produced excessively G-CSF, IL-1 alpha and a small amount of PTH-like factor. We confirmed that G-CSF and IL-1 alpha (hemopoietin 1) enhanced granulocytopoiesis and caused marked leukocytosis in vivo. Furthermore, we also demonstrated that PTH-rP and IL-1 alpha (a potent osteoclast-activating factor) synergistically stimulated bone resorption in vitro and also synergistically increased serum calcium concentration in vivo. Since we have demonstrated that at least two clonal cell lines derived from patients with hypercalcemia and leukocytosis produced G-CSF and IL-1 alpha, we presume that hypercalcemia and leukocytosis associated with some solid tumors may constitute a new paraneoplastic syndrome.
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PMID:A paraneoplastic syndrome of hypercalcemia and leukocytosis associated with solid tumors: production of interleukin 1 alpha (IL-1 alpha) and granulocyte colony-stimulating factor (G-CSF) by clonal squamous cell carcinoma cells. 247 Jun 24

Previously we reported that a clonal squamous cell carcinoma cell line (T3M-1) derived from a lower jaw cancer of a patient with marked leukocytosis and hypercalcemia produced factors containing a potent bone-resorbing activity (BRA) (Mr 15,000-20,000) and a colony-stimulating activity. To elucidate the pathogenesis of this humoral hypercalcemia, BRA and colony-stimulating activity in both the conditioned medium and cells were characterized. The conditioned medium, when eluted at neutral pH, contained colony-stimulating activity and thymocyte proliferation-stimulating activity, the latter of which comigrated with BRA. Upon elution with acetic acid (pH 2.0), the conditioned medium contained no interleukin 1-like activity but potent parathyroid hormone-like activity, which comigrated with BRA. Northern blot hydridization analysis revealed that T3M-1 cells produced constitutively mRNA for parathyroid hormone-related protein and granulocyte colony-stimulating factor. Furthermore, primer extension analysis revealed that the cells also produced mRNA for interleukin 1 alpha (IL-1 alpha). Since parathyroid hormone-related protein and IL-1 alpha (osteoclast-activating factor) synergistically increase the concentration of serum calcium, and since IL-1 alpha (hemopoietin 1) potentiates granulocyte colony-stimulating factor-induced granulocytopoiesis, we speculate that parathyroid hormone-related protein, granulocyte colony-stimulating factor, and IL-1 alpha are synergistically involved in a paraneoplastic syndrome of hypercalcemia and leukocytosis, at least in some patients with solid tumors.
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PMID:Paraneoplastic syndrome of hypercalcemia and leukocytosis caused by squamous carcinoma cells (T3M-1) producing parathyroid hormone-related protein, interleukin 1 alpha, and granulocyte colony-stimulating factor. 247 71

It is noted that while a wide variety of syndromes have been associated with hypernephroma in the clinical literature, there is clear understanding of the pathophysiology of these effects only in the cases of the endocrine disorders where direct tumor production of hormone can be demonstrated in vitro. Furthermore, this knowledge has done little to alter the care of patients with the disease, except for indications that indomethacin might be of benefit in some patients with hypercalcemia and that one might consider the use of converting enzyme inhibitors in patients with hypernephroma and hypertension. The overall approach to the disease is still surgical. Resection of the tumor also removes the paraneoplastic syndrome. Persistence or recurrence of a syndrome suggests the continued presence of the neoplasm, with the considerations for prognosis which that fact entails. To that degree, at least, these conditions are useful as tumor markers, but such use is limited because they are inconsistent. Further studies of pathophysiology of paraneoplastic syndromes will lead to better understanding of processes of cell differentiation and regulation, and possibly better ways to manage the patients in which they occur.
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PMID:Paraneoplastic syndromes in hypernephroma. 330 61

In order to elucidate the pathogenesis of humoral hypercalcemia and leukocytosis in a 71-year-old patient with squamous cell carcinoma of the thyroid, bone-resorbing activity (BRA) and colony-stimulating activity in the conditioned medium of T3M-5 cells, a clonal cell line established from the tumor, were studied. Gel chromatography of the concentrated conditioned medium revealed respective single peaks of colony-stimulating activity (Mr approximately 27,000) and BRA (Mr 15,000-20,000). BRA did not elicit parathyroid-hormone-like activity but greatly enhanced phytohemagglutinin-induced thymocyte proliferation. This interleukin 1 (IL-1)-like activity exactly coeluted with BRA upon gel chromatography, DEAE-Sepharose ion-exchange chromatography, and isoelectric focusing (pI, 4.7-5.2). BRA was partially inhibited by indomethacin and hydrocortisone, and completely inhibited by anti-IL-1 alpha antiserum, whereas anti-IL-1 beta antiserum had no effect. Furthermore, transplantation of T3M-5 cells into nude mice caused marked hypercalcemia as well as leukocytosis. These findings suggested that excessive production of colony-stimulating factor and IL-1 alpha-like factor by the squamous cell carcinoma was responsible for leukocytosis and hypercalcemia, respectively, in the tumor-bearing nude mice and in the patient. Since several similar cases have been reported in Japan, the syndrome of leukocytosis and hypercalcemia associated with certain solid tumors may constitute a new paraneoplastic syndrome.
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PMID:Production of interleukin 1 alpha-like factor and colony-stimulating factor by a squamous cell carcinoma of the thyroid (T3M-5) derived from a patient with hypercalcemia and leukocytosis. 349 74

Humoral hypercalcemia of malignancy is a common paraneoplastic syndrome which is characterized by hypercalcemia resulting from secretion by tumors of a circulating bone-resorbing factor. Evidence suggests that in many instances this factor is an adenylate cyclase-stimulating protein which shares features with, but is distinct from, parathyroid hormone (PTH). The current report describes the purification to homogeneity from a humoral hypercalcemia of malignancy-associated tumor of a novel, basic, highly potent PTH-like adenylate cyclase-stimulating protein. This factor differs from previously described PTH-like factors with respect to size, amino acid composition, and specific activity.
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PMID:Identification of a novel 17,000-dalton parathyroid hormone-like adenylate cyclase-stimulating protein from a tumor associated with humoral hypercalcemia of malignancy. 358 10


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