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Query: UMLS:C0221002 (primary hyperparathyroidism)
 4,921 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

Measurement of parathyroid hormone-related peptide (PTHrP) associated with that of parathyroid hormone, allows to establish, in most cases, diagnosis of hypercalcemia of malignancy and more exactly of patients with Malignancy Humoral Hypercalcemia (MHH). Because of the variety of molecular forms of PTHrP, linked to its catabolism, its immunoassay remains difficult. After a study evaluating the methodological reliability, we measured the contribution of PTHrP to the hypercalcemia by 2 assays: a N-terminal RIA and a 1-72 IRMA in samples from 47 control subjects, 10 patients with chronic renal failure (IRC), 13 patients with primary hyperparathyroidism (HPT), and 48 patients with solid tumors classified by their level of calcemia: 48 normocalcemia and 23 hypercalcemia. We noted a strong correlation (r = 0.92) between the two assays. They do not show increases in renal insufficiency; they have a good diagnostic discrimination between HPT, normal subjects and patients with MHH. Elevated levels of PTHrP are similar in both assays. However, IRMA appears to be more sensitive and more practical than RIA. Moreover, it shows the best correlation between serum calcium and phosphorus in patients with MHH.
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PMID:[Performances of two kits for parathyroid hormone-related peptide (PTHrP) assay in the additional study of malignant hypercalcemias]. 874 2

Brown tumour is one of the forms in which fibrous-cystic osteitis, which represents the terminal stage of the bone remodelling processes during primary or secondary hyperparathyroidism, is manifested. For years brown tumour was regarded as a typical lesion of primary hyperparathyroidism, but cases of brown tumours in patients with hyperparathyroidism secondary to renal failure were increasingly often reported in the literature. From an epidemiological point of view, the frequency of brown tumours in patients with renal insufficiency is extremely variable, as is the bone site affected. Several bone segments can be affected at once, but the ethmoid and frontal sinus are rarely reported. Symptoms are caused by the considerable dimensions of the brown tumour and its localisation: in the jawbones it may present sometimes painful, hard and clearly palpable swellings; if large, the tumour may deform the appearance of the bone segments affected or alter the function of the masticatory apparatus. In other cases, there is a complete absence of clinical symptoms and diagnosis may be totally coincidental during the radiological examinations. In histological terms, brown tumours are made up by a cell population consisting of rounded or spindle-like mononucleate elements, mixed with a certain number of plurinucleate giant cells, resembling osteoclastic cells, among which recent haemorrhagic infiltrates and hemosiderin deposits (hence the brown colour) are often found. The aim of this study was to report three cases from a population of 107 patients undergoing haemodialysis at the Turin University Centre. In conclusion, the localisation of maxillary brown tumours appears to prefer a young, female population; brown tumours are rarely an early sign of hyperparathyroidism in haemodialysis patients, but they often appear in conditions of advanced hyperparathyroidism which have escaped medical control either owing to unsuitable therapy or scant patient compliance; they are rapidly evolving lesions whose regression may be very slow or not occur even after total parathyroidectomy; the severity of the lesion caused by a brown tumour may lead to evident osteolysis in the maxillofacial district, thus suggesting the need for early and regular radiological screening; in the event of lesions which are already present, from the authors' point of view, the choice of treatment must be oriented towards parathyroidectomy.
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PMID:[Brown tumor of the jaws]. 902 91

During recent decades, primary hyperparathyroidism (pHPT) has appeared as one of the more common endocrine disorders. Previously, the disease was the obvious cause of severe, symptomatic bone disease, recurrent renal stones, and sometimes devastating muscular weakness. The condition often progressed rapidly and ultimately ended in renal insufficiency. Today, pHPT is frequently recognized in patients with less obvious symptoms and markedly slower disease progression. However, if thoroughly examined, many of these patients will also present typical symptoms and complications of the disease. Surgery in pHPT has also developed as a highly efficient procedure with low failure rate and few complications. Further, successful operation is likely to decrease the risk of developing long-term disturbances of calcium metabolism and recently recognized cardiovascular complications of the disease. However, in a group of generally elderly patients with especially mild hypercalcemia and no obvious symptoms, disease progression may be slow, and it is possible that some of these patients can be followed safely without surgery. These patients also constitute a majority of cases detected in population surveys. Pathophysiological studies of pHPT have revealed more or less disturbed secretory regulation as a characteristic feature of pathological parathyroid glands, and this accounts principally for the patients' hypercalcemia. This abnormality has been related to decreased expression or capacity of parathyroid cell surface receptors executing a crucial calcium-sensing function. Recent progress has also led to the identification of causes of a growth regulatory disturbance in pathological parathyroid glands. Exploration of molecular mechanisms behind these abnormalities are likely to further unveil disease characteristics and help explain differences in clinical symptoms and disease progression among the patients with pHPT.
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PMID:Non-familial primary hyperparathyroidism. 908 66

In humans plasma parathyroid hormone (PTH) fluctuates episodically at a frequency of 6-7 bursts per hour. Approximately 30% of circulating PTH is attributable to pulsatile secretion and 70% to tonic secretion. PTH release is tightly controlled by Ca2+. Acute hypocalcaemia elicits a biphasic wave of PTH release, with an initial selective amplification and acceleration of the pulsatile component followed by proportionate stimulation of pulsatile and tonic secretion. Acute hypercalcaemia submaximally suppresses the frequency and mass of PTH bursts as well as tonic PTH release. Patients with primary hyperparathyroidism exhibit proportionate increases in pulsatile and tonic secretion, with no change in pulse frequency. In secondary hyperparathyroidism due to renal insufficiency, tonic secretion and pulsatile burst mass are also proportionately amplified, and burst frequency is increased. Moreover, the hypocalcaemia-induced increase in burst frequency and mass as well as their suppression during hypercalcaemia is diminished, suggesting partial uncoupling of hyperplastic parathyroids from physiological regulatory mechanisms. While the secretory pattern of PTH and its dysregulation in disease states is now well defined, the functional significance of pulsatile PTH signalling for target tissues is still largely unexplored. Preliminary work indicates that intermittent, in contrast to continuous, PTH administration stimulates bone formation. Cell culture studies suggest PTH receptor down-regulation with tonic exposure.
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PMID:Pulsatile parathyroid hormone secretion in health and disease. 1075 73

Alterations of arterial vessel wall function are associated with increased cardiovascular morbidity and can be measured by noninvasive ultrasound techniques. There is increasing evidence that hyperparathyroidism contributes not only to structural changes of the cardiovascular system but to disturbances in functional arterial vessel wall properties. It has been shown that elevated concentrations of parathyroid hormone are associated with decreased arterial distensibility and increased intima-media thickness in patients with renal insufficiency. A permissive role of parathyroid hormone in the pathogenesis of uremic vessel wall changes has been discussed. The endothelium is a newly recognized target organ of parathyroid hormone. In patients with primary hyperparathyroidism endothelial dysfunction has been demonstrated, that seems to be reversible after parathyroidectomy. Effects on arterial vessel wall function may contribute to increased blood pressure observed in hyperparathyroidism. The complex cardiovascular effects of parathyroid hormone and changes in vascular tone, arterial distensibility and endothelial function in hyperparathyroidism are discussed.
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PMID:[Alterations of arterial vessel wall properties in hyperparathyroidism]. 1085 65

Hypercalcemia may develop as a consequence of a disturbance of one or more links within the feedback system of calcium homeostasis. Hypercalcemic diseases may be caused by the parathyroid glands as well as by their dependent end organs, the kidneys, the intestine, the skeleton. Partial parathyroid hormone activity can be produced by many tumour factors in a paraneoplastic way. Hypercalcemia induces the symptoms of the so-called hypercalcemic syndrome which should be familiar to the physician. Hints towards the cause may be the organ manifestation in case of primary hyperparathyroidism, in case of the other causal diseases they may present with typical components of their clinical picture. Diagnostics should start with the differentiation between parathyroid-related hypercalcemia (autonomous, primary hyperparathyroidism and variants) and the broad spectrum of non-parathyroid hypercalcemia, mainly accompanying malignancies. Symptomatic treatment of hypercalcemia often has to start before the definite diagnosis is confirmed. Later on, this merely symptomatic treatment may be replaced by causal treatment, as far as possible. Symptomatic treatment of hypercalcemia may follow the 'diuretic', the 'antiresorptive', or the 'antiabsorptive' way--the 'extractive' way by hemodialysis is the treatment of choice in case of hypercalcemic crisis accompanied by renal insufficiency.
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PMID:[Hypercalcemia]. 1089 25

A prospective study on the natural course of primary hyperparathyroidism has recently been reported. Since hyperparathyroidism in multiple endocrine neoplasia type 1 (MEN 1) is genetically distinct from most forms of sporadic hyperparathyroidism, it is important to know the natural course of hyperparathyroidism in MEN 1 for better clinical management. For this purpose, we retrospectively reviewed clinical parameters of patients with MEN 1 when they were diagnosed as having hyperparathyroidism, and compared them with those of patients with sporadic primary hyperparathyroidism. In patients with MEN 1: 1) levels of intact PTH (i-PTH) gradually increased with age, which accelerated over 40 years; 2) compared to the steep rise in i-PTH levels in aged patients, increase in serum calcium or decrease of serum inorganic phosphate concentration was relatively mild, and 3) the high concentrations of i-PTH in aged patients were not due to renal insufficiency. These features were not observed in patients with sporadic primary parathyroid adenomas. Clinical features of untreated hyperparathyroidism in MEN 1 may be significantly affected by the age of the patient. The effect, if any, of age-dependent deterioration on recurrence rate after subtotal or total parathyroidectomy requires further elucidation.
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PMID:Primary hyperparathyroidism in patients with multiple endocrine neoplasia type 1: comparison with sporadic parathyroid adenomas. 1154 65

Although the kinetics of intraoperative intact parathyroid hormone (iPTH) are well characterised in primary hyperparathyroidism, no data are available for patients with renal hyperparathyroidism and renal insufficiency, partially because of the high costs of intraoperative quick iPTH measurement. Therefore we evaluated an inexpensive laboratory test with a duration of 18 min for intraoperative use and measured iPTH intraoperatively in 34 patients with renal hyperparathyroidism. Samples were taken before and 5 min and 15 min after parathyroid resection. Blood samples were put on ice immediately and sent to the hospital central laboratory via a pneumatic tube system. The first 76 probes were measured in parallel using three assays: the Nichols Quick PTH, the Roche Elecsys and the Biermann Immulite assay. The subsequent samples were only measured using the Elecsys assay. Determination of iPTH from 76 samples showed a correlation coefficient of 0.997 between the Immulite and Elecsys assay and a correlation coefficient of 0.987 for the Nichols Quick PTH and the Elecsys test. In renal hyperparathyroidism the mean iPTH was 26+/-2% of the starting value 5 min after subtotal parathyroidectomy and 18+/-2% after 15 min. Renal function influenced absolute iPTH values in patients with renal hyperparathyroidism but not relative changes. In patients with terminal renal insufficiency iPTH decreased from 615+/-57 pg/m before preparation to 109+/-13 pg/ml 15 min after subtotal resection. In contrast in patients after kidney transplantation iPTH decreased from a lower starting value of 341+/-94 pg/ml to 58+/-9 pg/ml after 15 min. The iPTH kinetics showed a biphasic clearance of iPTH with an initial dominant half-life of 3.2 min and a terminal half-life of 29.2 min. Half-life did not correlate with renal function. All operations were successful as indicated by an adequate drop in PTH (from 709+/-92 pg/ml preoperatively to 22+/-6 pg/ml at discharge) and calcium (from 2.57+/-0.04 mmol/l to 2.32+/-0.04 mmol/l). In conclusion, intraoperative measurement of iPTH is also reliable in patients with renal hyperparathyroidism. Elimination kinetics are similar to that in patients with primary disease. However, the half-life was not influenced by renal function. The availability of a quick, inexpensive, routine iPTH test might expand its use to renal hyperparathyroidism, specifically for surgical decisions in problem cases.
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PMID:Intraoperative measurement of intact parathyroid hormone in renal hyperparathyroidism by an inexpensive routine assay. 1173 18

Severe hypercalcemia is a life-threatening medical emergency. It is most commonly caused by malignant tumors, but can also be caused by primary hyperparathyroidism or less often by a dysregulated production of active vitamin D in granulomatous disorders. Symptoms include nausea, vomiting, renal insufficiency, severe dehydration, lethargy, confusion, and even coma. Severity of symptoms, calcium concentrations, and the overall status of the patient are important considerations in selecting appropriate therapy. Hydration to correct volume depletion is the cornerstone of acute therapy. Loop diuretics may be added to saline hydration after extracellular fluid volume has been replenished to enhance urinary calcium excretion and mitigate fluid overload from rehydration. Calcitonin and intravenous infusion of bisphosphonates reduce serum calcium levels by interfering with calcium release from the skeleton. Dialysis with a low or zero calcium dialysate is reserved for patients who are refractory to these measures. Corticosteroids are effective with hypercalcemia due to increased vitamin D levels and in multiple myeloma.
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PMID:[Hypercalcemic crisis]. 1468 84


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