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)

Although urinary measurements of collagen degradation provide valid estimates of bone resorption, their clinical application is hampered by pronounced analytical and biological variability. Therefore, immunoassays for the determination of such parameters in serum have been developed. In this study, we assessed the performance of three new serum markers of bone turnover, i.e., C-terminal and N-terminal telopeptides of type I collagen (S-CTX and S-NTX) and bone sialoprotein. Results were compared with urinary total pyridinoline, total deoxypyridinoline, and urinary C-terminal telopeptides of type I collagen (U-CTX) and urinary N-terminal telopeptides of type I collagen (U-NTX). The study population included healthy men (n = 27), premenopausal (n = 30) and postmenopausal (n = 31) women, patients with hepatic dysfunction (HF, n = 24), renal failure (RF, n = 30), breast cancer without (BC-, n = 24) and with (BC+, n = 30) bone metastases, primary vertebral osteoporosis (OPO, n = 27), primary hyperparathyroidism (PHPT, n = 16), active Paget's disease of bone (n = 18), multiple myeloma (MM, n = 18), and patients with hypercalcemia of malignancy before and after treatment with pamidronate (HOM, n = 28). Changes in urinary and serum markers were similar in most metabolic bone diseases. However, differentiation between healthy controls and OPO, or PHPT, was improved by the serum markers. In MM, all serum and urinary markers were elevated (p < 0. 05 vs. controls). In BC+, skeletal involvement was reflected by significant increments in all indices (p < 0.01 vs. BC-), except U-CTX and S-CTX. In HOM, pamidronate-induced changes in biomarkers were most pronounced for U-CTX and S-CTX and S-NTX. HF and RF were associated with elevated levels of all serum markers (p < 0.05 vs. controls). In conclusion, measurements in serum reflect bone resorption to the same extent as the urinary indices. Since serum markers circumvent some of the limitations of urinary measurements, their use potentially improves the assessment of skeletal disorders.
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PMID:Novel serum markers of bone resorption: clinical assessment and comparison with established urinary indices. 1032 May 28

Calciphylaxis is a rare disorder associated with calcification of small- and medium-sized blood vessels, and progressive skin necrosis usually seen in the setting of end-stage renal disease (ESRD) and secondary hyperparathyroidism. It has also been observed in primary hyperparathyroidism, hypercalcemia of malignancy (extensive bony metastasis of breast cancer), and an isolated case reported with end-stage liver disease. We report an unusual case of calciphylaxis associated with metastatic breast carcinoma in the absence of renal or parathyroid disease. Calciphylaxis has generally been associated with end-stage renal disease and hyperparathyroidism. One previous case report described calciphylaxis occurring in a patient with metastatic adenocarcinoma of the breast and hypercalcemia. Our case represents the second reported case of calciphylaxis associated with osteolytic, metastatic breast cancer. Although ESRD with secondary hyperparathyroidism is the most common presentation of calciphylaxis, this case demonstrates that other conditions that alter normal calcium metabolism must be considered in the differential diagnosis.
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PMID:Calciphylaxis associated with metastatic breast carcinoma. 1042 13

The purpose of the study was to give an overview over the usefulness of ultrasonographic examination of parathyroid glands in dogs. By means of a 10 MHz high-resolution linear transducer it was possible to visualize parathyroid glands in healthy dogs. There was a positive correlation between body weight and size of the parathyroid glands, additionally the likelihood to detect 4 glands increased with an increase in body weight. Dogs with chronic renal failure had significantly larger parathyroid glands than healthy dogs and dogs with acute renal failure. In dogs with hypercalcemia of malignancy either none or parathyroids which were small in relation to body weight were detected. In contrast visualisation of parathyroid masses in dogs with primary hyperparathyroidism was easy due to their increased size and anechoic appearance. In dogs with severe azotemia the ultrasonographic examination of the parathyroid glands is helpful to differentiate between acute and chronic renal failure, in dogs with hypercalcemia to differentiate between hypercalcemia of malignancy and hypercalcemia due to primary hyperparathyroidism.
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PMID:[Ultrasonography of the parathyroid glands in dogs--a review]. 1123 25

The etiology, pathophysiology, and diagnosis of hypercalcemia associated with malignant diseases are discussed. In humans, calcium is controlled by three mechanisms: parathyroid hormone, which regulates bone resorption and renal reabsorption of calcium; calcitonin, an antagonist of parathyroid hormone; and cholecalciferol, which regulates calcium absorption from the gastrointestinal tract. Hypercalcemia of malignancy (HCM) results primarily from increased bone resorption by osteoclasts and, to a lesser extent, from increased renal tubular reabsorption. In most tumors, parathyroid hormone-related protein (PTHrP) is the primary mediator of calcium. PTHrP stimulates increased bone resorption by osteoclasts. This stimulation also activates transforming growth factor-beta (TGF-beta), which stimulates tumor cells, thus perpetuating the cycle. Hypercalcemia is usually defined as a serum calcium concentration greater than 12 mg/dL, corrected for the serum albumin concentration. In diagnosing HCM, it is important to rule out other causes of hypercalcemia, such as primary hyperparathyroidism.
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PMID:Overview of hypercalcemia of malignancy. 1175 5

Bisphosphonates (BP) are pyrophosphate analogs that include very potent inhibitors of bone resorption. BPs act directly on the osteoclast, suppressing isoprenylation by inhibiting farnesyl diphosphate synthase in the cholesterol pathway, which causes osteoclast inactivation. BPs should therefore reduce the bone loss produced by any cause, including hyperparathyroidism and hypercalcemia of malignancy (MIH), caused by parathyroid hormone (PTH) and PTH-related protein (PTHrP), respectively. BPs at higher doses than used in osteoporosis are indeed the treatment of choice for malignancy-induced hypercalcemia. Limited, but convincing, data show that BPs at doses effective in osteoporosis also reverse bone loss associated with mild primary hyperparathyroidism (PHPT).
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PMID:Bisphosphonates and primary hyperparathyroidism. 1241 93

Calciphylaxis is a poorly understood and highly morbid syndrome of vascular calcification and skin necrosis. Hypercalcemia, hyperphosphatemia, and secondary hyperparathyroidism are the factors implicated in the pathogenesis of calciphylaxis, which is generally identified in patients with hyperparathyroidism secondary to end-stage renal disease. It has also been observed in primary hyperparathyroidism, end-stage liver disease, and rheumatoid arthritis, in the absence of renal disease. There are few case reports of calciphylaxis occurring in hypercalcemia of malignancy. An unusual case is reported of calciphylaxis associated with malignant melanoma of the soft parts in the absence of renal or parathyroid disease. This is the first reported case of this soft tissue sarcoma showing calciphylactic changes.
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PMID:Malignant melanoma of the soft parts showing calciphylaxis. 1255 24

For the present, bisphosphonates are widely applicable;secondary osteoporosis, metastatic bone diseases, primary hyperparathyroidism, osteogenesis imparfecta, inflammatory bone and joint disorders besides primary osteoporosis, hypercalcemia of malignancy, Paget's disease of bone, and so on. More expansion of its clinical application in the future is greatly expected with elucidation of the mechanism of action.
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PMID:[Clinical application of bisphosphonates, present and future]. 1577 49

The two most common causes of hypercalcemia are primary hyperparathyroidism and neoplastic disease. Parathyroidectomy is the only curative intervention for the former condition. In the rare cases of patients with primary hyperparathyroidism who present with clinical symptoms due to their hypercalcemia, pharmacological treatment may be required. Fluid repletion and intravenous (IV) administration of bisphosphonates are recommended in the literature. Calcium receptor agonists (calcimimetic agents) are at the present time only available for use within clinical trials. Cancer patients usually present with symptoms of hypercalcemia. Rapid institution of antihypercalcemic treatment is essential in preventing life-threatening deterioration. Fluid repletion and administration of bisphosphonates are the treatment mainstays in hypercalcemia of malignancy. Five bisphosphonates are currently licensed in Europe for treatment of tumor-associated hypercalcemia: etidronate, clodronate, pamidronate, ibandronate, and zoledronate. In the US, pamidronate and zoledronate are licensed for use in this indication. Bisphosphonates containing nitrogen atoms (e.g. pamidronate, ibandronate, and zoledronate) are more potent than those without (e.g. etidronate, clodronate, and tiludronate). In patients with malignant hypercalcemia, the efficacy of the individual bisphosphonate depends on dose administered and initial serum calcium concentration. At present, pamidronate has been studied in the greatest number of investigations and in the largest number of patients. In the literature, the efficacy of pamidronate in restoring normocalcemia ranges between 40% and 100%, depending on the dose used and baseline serum calcium concentration. More recently, one study reported that pamidronate was inferior to zoledronate. In this study, the duration of response was also longer in the two zoledronate groups (30 and 40 days) than in the pamidronate group (17 days). The most serious adverse events of bisphosphonates concern renal function. Increases in serum creatinine levels have been more frequently reported following treatment of tumor-associated hypercalcemia with etidronate (8%) and clodronate (5%) than with the nitrogen-containing bisphosphonates pamidronate (2%) and ibandronate (1%). The frequency of increases in serum creatinine levels following treatment with zoledronate is difficult to estimate. Administration of the nitrogen-containing bisphosphonates has been associated with transient (usually mild) fever, lymphocytopenia, malaise, and myalgias. These events occur within 36 hours of the first dose and are self-limiting. Hypocalcemia occurs in up to 50% of patients treated with bisphosphonates for hypercalcemia of malignancy, although symptomatic hypocalcemia is rare. The toxicity and low efficacy of plicamycin (mithramycin) mean that use of this agent should be restricted to patients with hypercalcemia of malignancy who fail to respond to IV bisphosphonates. Calcitonin is characterized by good tolerability but poor efficacy in normalizing the serum calcium level. However, a major advantage of calcitonin is the acute onset of the hypocalcemic effect, which contrasts with the delayed but more pronounced effect of bisphosphonates. Combination calcitonin and bisphosphonate treatment may therefore be of value when rapid reduction of serum calcium is warranted. Gallium nitrate may be a valuable treatment for hypercalcemia of malignancy. It is characterized by high efficacy and few adverse events apart from renal toxicity (10% of cases). However, data are very limited and further trials are necessary.
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PMID:Current management strategies for hypercalcemia. 1596 62

Calciphylaxis is a relatively rare disorder associated with calcification of small- and medium-sized blood vessels, progressive ischemic skin necrosis, and ulcerations. It is usually seen in patients with end-stage renal disease with secondary hyperparathyroidism and is occasionally seen in primary hyperparathyroidism, hypercalcemia of malignancy, and end-stage liver disease. We report an unusual case of calciphylaxis seen in association with metastatic breast carcinoma in the absence of end-stage renal or parathyroid disease. A 73-year-old woman presented with painful leg ulcers. Serum calcium levels and parathormone levels were within normal limits. Skin biopsies from the ulcers revealed small- to medium-sized subcutaneous arteries with calcification of the media. Some of the arteries were narrowed by fibrointimal hyperplasia and fibrin thrombi. Calcification of the subcutaneous fat, fat necrosis, and suppuration were also seen. Calciphylaxis associated with metastatic osteolytic breast carcinoma is rare. Although end stage renal disease with secondary hyperparathyroidism is the most common cause of calciphylaxis, this case demonstrates that less common conditions with normal serum calcium and parathormone levels may also cause it.
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PMID:Unusual case of calciphylaxis associated with metastatic breast carcinoma. 1766 77

Primary hyperparathyroidism and malignancy are responsible for greater than 90% of all cases of hypercalcemia. Compared with the hypercalcemia of malignancy, hyperparathyroidism tends to be associated with lower serum calcium levels (< 12 mg/dL) and a longer duration of hypercalcemia (more than 6 months). The hypercalcemic symptoms are usually fewer and subtle. Hyperparathyroidism tends to cause kidney calculi, hyperchloremic metabolic acidosis, and the characteristics of metabolic bone disease osteitis fibrosa cystica, but no anemia. In contrast, hypercalcemia of malignancy is typically rapid in onset, with higher serum calcium levels, and more severe symptoms. Patients so affected show marked anemia, but they never have kidney calculi or metabolic acidosis. Parathyroid hormone assay is the most useful test for differentiating hyperparathyroidism from malignancy and other causes of hypercalcemia. In hyperparathyroidism, serum parathyroid hormone levels will be elevated. In other cases, the high serum calcium concentration usually results in suppression of parathyroid hormone. Treatment of hypercalcemia should be started with hydration. Loop diuretics may be required in individuals with renal insufficiency or heart failure to prevent fluid overload. Calcitonin is administered for the immediate short-term management of severe symptomatic hypercalcemia. For long-term control of severe or symptomatic hypercalcemia, the addition of biphosphonate is typically required. Among intravenous bisphosphonates, zoledronic acid or pamidronate are the agents of choice. Glucocorticoids are effective in hypercalcemia due to lymphoma or granulomatous diseases. Dialysis is generally reserved for those with severe hypercalcemia complicated with kidney failure.
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PMID:Hypercalcemia: an evidence-based approach to clinical cases. 1939 81


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