Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0221002 (primary hyperparathyroidism)
 4,921 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hypercalcemia of malignancy is due either to local osteolysis at the site of bone metastases or to production by the malignancy of parathyroid hormone-related peptide, which shares some of the effects of parathyroid hormone. We used a radioimmunoassay (antiserum specific to the amino-terminus) to measure serum parathyroid hormone-related peptide levels in controls (n = 61), chronic renal failure patients (n = 10), patients with primary hyperparathyroidism (n = 19), cancer patients with (n = 35) or without (n = 57) hypercalcemia and/or bone metastases (n = 53 and n = 39, respectively), and patients with hematologic malignancies (n = 15). We set the upper limit of normal of the parathyroid hormone-related peptide assay at 2.7 pmol/L. The peptide was undetectable in two-thirds of healthy controls. Renal failure did not interfere with the assay. Eighteen of the 19 patients with primary hyperparathyroidism had normal levels. In contrast, 82% of patients with humoral hypercalcemia of malignancy (i.e., without detectable bone metastases) had increased levels; in this subgroup there was a significant inverse correlation between serum levels of the peptide and phosphorus. Elevation of parathyroid hormone-related peptide levels was less common among hypercalcemic patients with metastatic bone disease (38%). Four of the seven hypercalcemic patients with hematologic malignancies had elevated parathyroid hormone-related peptide levels. In our overall study population, serum calcium levels were weakly but significantly correlated with parathyroid hormone-related peptide levels. In conclusion, elevated parathyroid hormone-related peptide in a patient with hypercalcemia suggests a malignant disease.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Contribution of parathyroid hormone-related peptide to the evaluation of hypercalcemia. 778 31

Severe hypercalcemia is mainly caused by inappropriately high concentrations of compounds which promote bone resorption, in particular PTH, PTHrP, or 1,25 (OH)2D3. The major consequences are impaired central nervous system and kidney function (polyuria/dehydration); the latter, in turn, aggravate hypercalcemia via decreased fluid intake, mobility, and renal calcium clearance. The most common causes of hypercalcemia are primary hyperparathyroidism and tumors, drugs (in particular thiazides, lithium, vitamin D and vitamin A and their derivatives), granulomatous and infectious diseases. The patient with mild hypercalcemia should be controlled (and if necessary operated on for adenoma of the parathyroid glands), while the patient with acute severe hypercalcemia needs to be treated immediately by (1.) 0.9% NaCl i.v. to restore plasma volume, (2.) bisphophonates i.v. to block bone resorption, and (3.) therapy for the underlying disorder.
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PMID:[Hypercalcemia]. 802 86

Hypercalcemia is most commonly associated with primary hyperparathyroidism and malignancy due to parathyroid hormone-related protein (PTHrP). Primary hyperparathyroidism is characterized by excessive secretion of parathyroid hormone in association with hypercalcemia. The modern presentation of primary hyperparathyroidism is as an asymptomatic disorder. Diagnostic tools such as bone mineral densitometry, bone histomorphometry, and the measurement of markers of bone turnover, as well as other clinical assessments, have all led to the development of guidelines to help direct decisions for parathyroid surgery or for medical management. Hypercalcemia of malignancy is often distinguishable from primary hyperparathyroidism by the presence of an obvious tumor. Primary hyperparathyroidism is excluded by the immunoradiometric assay for parathyroid hormone, which is suppressed. A number of clinical characteristics of hypercalcemia of malignancy can be explained on the basis of the tumor product, PTHrP, which directly causes hypercalcemia in many cases. Assays for PTHrP show elevated levels in patients in whom hypercalcemia is associated with the classic syndrome. Recent recognition that PTHrP is found ubiquitously in virtually all normal tissues and that it is possibly involved in a number of normal physiologic processes, apart from its pathologic role, provides an exciting basis for future research.
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PMID:Primary hyperparathyroidism and parathyroid hormone-related protein. 806 Jul 69

Ectopic tumoral secretion of authentic PTH is rare, as only four cases have been convincingly documented by demonstrating the presence of PTH messenger ribonucleic acid in tumor tissue. We report the case of a 25-yr-old male with biochemical alterations typical of primary hyperparathyroidism (elevated calcemia and renal tubular reabsorption of calcium, decreased phosphatemia and maximal tubular reabsorption of phosphate, and increased intact PTH serum levels). Extensive cervical exploration did not reveal any abnormally enlarged parathyroid tissue, but excision of a palpable superior retrosternal mass led to the correction of all abnormal biochemical values. Histological analysis showed a predominantly epithelial thymoma, without any detectable parathyroid gland on serial slices. Tumor extracts contained immunoreactive PTH material, with serial dilutions paralleling PTH standards in an immunoradiometric assay. By contrast, immunoreactive PTH-related protein was absent. Furthermore, on Northern blot analysis, there was a PTH messenger ribonucleic acid transcript with a size similar to that found in parathyroid adenoma or hyperplasia. The thymoma epithelial cells stained positively with antiserum against PTH-(1-34), but negatively with antichromogranin-A antiserum. These results support the ectopic production of authentic PTH by a thymoma and indicate a novel tumoral cause of primary hyperparathyroidism.
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PMID:A thymoma as a cause of true ectopic hyperparathyroidism. 807 82

Primary hyperparathyroidism (PHPT) is found not uncommonly in patients with cancer. In this report, however, we describe a patient where both humoral hypercalcaemia of malignancy and PHPT were present coincidentally. A 47-year-old man was found to have PHPT due to parathyroid hyperplasia. Serum parathyroid hormone (PTH) levels, which were elevated before parathyroidectomy, were undetectable post-operatively; however, hypercalcaemia persisted. Nephrogenous cyclic adenosine monophosphate was elevated along with this undetectable PTH, indicative of the presence of a PTH-like factor in the serum. This was confirmed by the finding of an elevated level of PTH-related protein (PTHrP) in plasma (9.1 pmol/l, normal < 2.6 pmol/l). Secondary carcinoma was identified in a lesion in the region of the manubrium sternii. This stained positively for PTHrP by immunocytochemistry and PTHrP messenger RNA was detected by in-situ hybridization. This case illustrates the value of sensitive PTH assays in distinguishing PHPT from other causes of hypercalcaemia and also shows the importance of considering primary hyperparathyroidism in the differential diagnosis of the patient with cancer and hypercalcaemia.
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PMID:Coincidental occurrence of primary hyperparathyroidism and cancer-associated hypercalcaemia in a middle-aged man. 831 76

The principal pathophysiologic alteration in severe hypercalcemia accompanying hyperparathyroidism and malignancy is enhanced osteoclastic bone resorption. Hypercalcemia impairs renal mechanisms that lead to sodium and calcium excretion; PTH and PTHrP acting on renal tubules enhance further calcium reabsorption. Although rehydration is often necessary as an initial therapy of hypercalcemia, the cornerstone of therapy is to inhibit osteoclastic bone resorption. The bisphosphonates, plicamycin, gallium, and calcitonin all inhibit osteoclastic bone resorption. Calcitonin is the most rapidly acting agent. Toxicities of calcitonin are minimal, yet its therapeutic efficacy is limited by lack of potency and tachyphylaxis. The second-generation bisphosphonates such as pamidronate represent a class of compounds that are extremely effective in inhibiting the metabolic function of the osteoclast. Given in a single infusion, a significant majority of patients will have normalization of corrected serum calcium lasting, on average, 1-2 weeks. Therapeutic benefit will be of greater duration because most patients remain only minimally symptomatic until corrected serum calcium rises above 11.5 mg/dL. Side effects of low-grade fever, hypophosphatemia, hypomagnesemia, and hypocalcemia may occur. Gallium nitrate is a potent inhibitor of bone resorption and may be of increased clinical value when more efficient administration protocols can be developed. Plicamycin, available for two decades, has cumulative toxicities and is less potent than the aminobisphosphonates. Renal insufficiency often accompanies severe hypercalcemia. The nephrotoxicity of gallium nitrate and plicamycin should preclude their use when there is moderate impairment of renal function, and amino bisphosphonates become the treatment of choice in these patients. Although several authors have advocated individualized approaches to the management of hypercalcemia, the potency and duration of action of the aminobisphosphonates make them a reasonable treatment choice for most patients with symptomatic hypercalcemia. Most importantly, the most effective therapy for hypercalcemia is to recognize and treat the underlying disease. Acute primary hyperparathyroidism requires surgery. The effective treatment of hypercalcemia of malignancy allows the introduction of tumor-specific therapy, limits morbidity, and shortens and deintensifies hospitalization. At times, the most appropriate and compassionate decision (particularly in patients with malignancy who have exhausted all therapeutic options and have relentless bone pain) is to withhold therapy for hypercalcemia. Future therapies directed at the osteoclast, such as more potent later-generation bisphosphonates; inhibitors of osteoclast attachments and inhibitors of peptides, which stimulate osteoclastic bone resorption, may permit safe, easily administered, outpatient therapies that will improve the quality of life for hypercalcemic patients.
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PMID:Pathophysiology and management of severe hypercalcemia. 832 91

Recent reports have described clinical benefits of all-trans-retinoic acid (ATRA) therapy for acute promyelocytic leukemia (APL). This paper describes severe hypercalcemia (serum calcium: 18.7 mg/dl) in association with ATRA treatment in a 14 year old girl with APL. Serum parathyroid hormone (PTH) concentrations were normal (0.21 ng/ml), which precludes the possibility of primary hyperparathyroidism or ectopic PTH secretion as a cause of the hypercalcemia. As for the factors which can accelerate mineral resorption, there were no apparent increases in the levels of PTH-related protein (PTH-rP), prostaglandins and vitamin D metabolites. In our in vitro experiment, ATRA did not stimulate the leukemic cells to produce PTH-rP. We speculate that ATRA, like PTH, may increase osteoclastic activity and induce hypercalcemia.
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PMID:Hypercalcemia associated with all-trans-retinoic acid in the treatment of acute promyelocytic leukemia. 850 72

The occurrence of aluminum-related bone disease should be completely prevented in uremic patients by restricting the use of aluminum-phosphate binders, which can be safely replaced by oral calcium carbonate. Factors other than aluminum may lead to adynamic bone disease in uremic patients. Radiolucent bone cysts are indicative of amyloid deposits, and their occurrence and progression may be influenced by the membranes used for hemodialysis. Bone disease may persist after successful renal transplantation, and the additional deleterious effect of immunosuppressive drugs should be emphasized. Primary hyperparathyroidism is the most frequent cause of hypercalcemia in the general population. Surgery should be undertaken when there is evidence of active disease, even in asymptomatic patients. The consequences of primary hyperparathyroidism on bone mass and bone fragility remain controversial, and histologic bone studies suggest that hyperparathyroidism leads to increased bone turnover without any deleterious effect on bone volume or trabecular architecture. The diagnostic value of a newly developed immunoassay for intact parathyroid hormone and parathyroid hormone-related protein is clearly demonstrated. New bisphosphonates are of major value for the management of hypercalcemia in malignancy.
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PMID:Renal osteodystrophy and hypercalcemia. 851 74

Bone and vitamin D metabolism are examined in patients with primary hyperparathyroidism (1 degree HPT), humoral hypercalcemia of malignancy (HHM), and local osteolytic hypercalcemia (LOH) with normal renal function. Among the bone resorption markers, T scores of total deoxypyridinoline (Dpyd) were highest in HHM and were significantly higher than those in 1 degree HPT. Among the formation markers, T scores of osteocalcin (OC) were highest in 1 degree HPT but were negative in HHM. The elevation in total Dpyd was associated with an increase in OC in 1 degree HPT, and the ratios of total Dpyd/OC were similar to those in controls. In contrast, many patients with HHM and LOH exhibited elevated total Dpyd and suppressed OC with increased total Dpyd/OC ratios, but the ratios varied widely. Serum 1,25-dihydroxyvitamin D [1,25(OH)2D] was elevated in 1 degrees HPT but was suppressed in HHM and LOH at any serum Ca levels. These results demonstrate that increased bone resorption is associated with enhanced bone formation in 1 degrees HPT but are uncoupled in many of the HHM and LOH patients, and that total Dpyd/OC ratio can be a useful index to estimate the coupling state of bone. It is suggested that the reduction in serum 1,25(OH)2D cannot be explained by an elevation in serum Ca in HHM and LOH, and that the differences in bone and vitamin D metabolism in HHM and LOH from those in 1 degree HPT may be caused by a common mechanism such as the secretion of some cytokines from tumors.
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PMID:Differences in bone and vitamin D metabolism between primary hyperparathyroidism and malignancy-associated hypercalcemia. 863 76

Hypercalcemia in patients with cancer may reflect the synthesis and secretion into circulation of parathyroid hormone-related protein (PTHrP) produced by the tumor. In the present study, we have measured circulating PTHrP concentrations in healthy subjects and patients using a new immunoradiometric assay (IRMA) that is specific for the 1-86 amino acid sequence of molecule, and in plasma collected with protease inhibitors. Plasma concentrations of PTHrP(1-86) were greater than the detection limit of the assay (0.3 pmol/l) in healthy subjects. All patients with hypercalcemia-associated cancer had PTHrP(1-86) levels significantly greater (median 7.74 pmol/l, P < 0.05) than healthy subjects or patients with cancer and normal serum calcium, primary hyperparathyroidism and hyperparathyroidism secondary to chronic renal failure. Plasma PTHrP and corrected serum calcium were correlated in patients with hypercalcemia-associated cancer. In one patient, a marked decrease in PTHrP and calcium levels was observed following surgery. Our results suggest that this IRMA for PTHrP(1-86) may be useful for diagnosis and monitoring of PTHrP-producing tumors induced hypercalcemia.
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PMID:Plasma parathyroid hormone related-protein levels in patients with cancer, normocalcemic and hypercalcemic. 871 34


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