Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020437 (hypercalcemia)
 10,293 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Primary hyperparathyroidism is a relatively common disease in elderly women. Many of its clinical presentations may be confused with normal aging. Among the elderly, renal dysfunction and skeletal disease, particularly osteoporosis, are the two aspects of the disease likely to cause the most morbidity. It is increasingly apparent, however, that a large group of patients with hyperparathyroidism are asymptomatic or only mildly symptomatic. When symptoms are present, or repeated serum calcium levels all exceed 11.0 mg/dL, surgery is considered the treatment of choice. Success of surgery and of postoperative recovery are not affected by the age of the patient, but are enhanced by the experience of the surgeon performing the parathyroidectomy. There are difficult management decisions to be made concerning the elderly asymptomatic patient with mild hypercalcemia. A conservative approach to therapy for these individuals would include maintenance of adequate hydration, and involvement in physical activity. Dietary restriction of calcium should be recommended only as long as there is no evidence that it is exacerbating negative calcium balance. Drugs likely to worsen hypercalcemia, such as thiazides, must be avoided, and blood chemistries should be monitored at regular intervals. Because the bone loss of hyperparathyroidism may develop insidiously, serial bone density measurements are probably reasonable in older women already at risk for osteoporosis. Accelerated bone loss is an indication for surgical intervention. A wide variety of medications have been proposed for the treatment of primary hyperparathyroidism, but none stands out as a particularly desirable therapeutic alternative. Future research in this area, particularly with the use of estrogens in postmenopausal women with hyperparathyroidism, may eventually lead to greater acceptance of this alternative to surgery.
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PMID:Primary hyperparathyroidism in the elderly. 304 33

Many factors, such as interleukin 1, transforming growth factor alpha, tumour necrosis factor alpha and beta, and prostaglandins, have been implicated in the pathogenesis of the humoral hypercalcaemia of malignancy (Mundy and Martin, 1982; Martin and Mundy, 1987; Mundy et al, 1984). Much interest in the past has also centred upon the likelihood of ectopic secretion of PTH in this condition. We have purified a protein (PTHrP) implicated in HHM from a human lung cancer cell line (BEN). Full-length cDNA clones have been isolated and found to encode a pre-pro-peptide of 36 amino acids and a mature protein of 141 amino acids. Eight of the first 13 amino acids were identical with human PTH, although antisera directed to the aminoterminus of PTHrP do not recognize PTH; this homology is not maintained in the remainder of the molecule. PTHrP therefore represents a previously unrecognized hormone, possibly related to the PTH gene by a gene duplication mechanism. In support of this notion, the PTHrP gene has been localized to the short arm of chromosome 12; it is believed that chromosome 11, containing the PTH gene, and chromosome 12 are evolutionarily related. In addition, the human PTHrP gene has been isolated, characterized, and shown to have an intron-exon arrangement that is more complex than the PTH gene. It is possible that the original ancestral gene is indeed the PTHrP gene; resolution of this question awaits studies in lower species. Peptides synthesized to the predicted protein sequence have allowed detailed structure-function studies that have identified aminoterminal sequences to be responsible for the biological effects of the molecule. Antibodies raised against the various synthetic peptides have led to the immunohistochemical localization of PTHrP in many human squamous cell carcinomas as well as in a subpopulation of keratinocytes of normal skin. The availability of these antibodies has opened the way for the development of a radioimmunoassay to detect PTHrP in the sera of cancer patients at risk of developing hypercalcaemia. The recent characterization of PTHrP-like activity in the ovine fetus suggests some physiological function for PTHrP. It is possible that PTHrP, as the fetal counterpart of PTH, has the role of maintaining the maternal-fetal calcium gradient. The isolation and characterization of PTHrP has added to our understanding of the mechanisms of hypercalcaemia and may contribute to the understanding of other metabolic bone diseases, such as osteoporosis and Paget's disease. Finally, and perhaps most importantly, PTHrP may play a hitherto unrecognized role in normal cell physiology.
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PMID:Parathyroid hormone-related protein: a novel gene product. 307 45

This is a report of six patients with cirrhosis of the liver in whom primary hyperparathyroidism occurred due to a solitary parathyroid adenoma 3 months to 9 years after undergoing emergency portacaval shunt for hemorrhage from esophageal varices. The presenting symptoms in all six patients were weakness and bone pain. Three patients had a bone fracture after insignificant trauma, one and probably two passed kidney stones, and a duodenal ulcer developed in two. Bone x-ray films showed generalized osteoporosis in all patients. Renal function and arterial blood pH were within normal limits in every patient. The diagnosis of primary hyperparathyroidism in each patient was based on repeated demonstrations of hypercalcemia, hypophosphatemia, and markedly elevated serum immunoreactive parathyroid hormone concentrations. In all six patients, removal of the parathyroid adenoma resulted in disappearance of symptoms; normalization of serum calcium, phosphorus, and immunoreactive parathyroid hormone levels; and in four of the six, improvement in radiographic evidence of osteoporosis during follow-up of from 1 to 6 years. The association of cirrhosis, portacaval shunt, and primary hyperparathyroidism has not been documented previously. Our six patients with primary hyperparathyroidism constitute 3.4 percent of 174 survivors of emergency portacaval shunt in a series of 264 unselected, consecutive patients with cirrhosis and bleeding esophageal varices. Hepatic osteodystrophy is known to have occurred in only 11 of these 174 survivors. Primary hyperparathyroidism may be a more common cause of hepatic osteodystrophy than has been previously recognized, and should be considered in patients with cirrhosis in whom weakness, bone pain, and bone demineralization develop, particularly if they have a portacaval anastomosis.
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PMID:Hyperparathyroidism, cirrhosis, and portacaval shunt. A new clinical syndrome. 325 57

Calcitriol was compared with placebo in the treatment of postmenopausal osteoporosis in a double-blind, randomized, parallel clinical trial of 24 months' duration. Adjustment was made in dietary calcium to maximize the dose of calcitriol. The study was completed by 15 patients who received placebo and 12 patients who received calcitriol. The calcitriol group had positive slopes (compared with negative slopes for the placebo group) for total body calcium, bone mineral content of the radius, bone mineral density of the lumbar spine, and radiographic absorptiometry of the middle phalanges. The difference between the two groups was statistically significant for each of these measurements. The fracture rate in the treatment group was 250 per 1,000 patient-years as compared with 333 for the placebo group. The mean dose of calcitriol was 0.8 micrograms per day. Hypercalcemia, hypercalciuria, and perhaps nephrolithiasis were observed as complications of treatment. Calcitriol increased bone mineral density by decreasing bone resorption, but not by increasing bone formation. Future studies should concentrate on treatment with oral calcitriol in lower doses. It would also be of interest to examine parenteral administration of calcitriol. It is possible that bone formation can be increased by achieving higher serum levels of the drug, whereas complications may be avoided by using a non-oral route of administration.
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PMID:Calcitriol in the treatment of postmenopausal osteoporosis. 327 69

Radionuclide imaging with Tc-99m diphosphonates is not an effective method for detecting or ruling out most osteoporotic diseases including senile osteoporosis or accelerated postmenopausal osteoporosis, and the slow loss of bone tissue generally remains undetected by this modality. Nonetheless, it frequently surpasses or supplements radiographic findings in evaluating the focal complications of metabolic bone disease, including fractures, microfractures, stress fractures, vertebral compressions, Milkman-Looser zones, aseptic necrosis, and acute infarction. In contrast to its secondary role in osteoporosis, bone imaging is of prime importance in investigating hypercalcemia, because the major cause of this abnormality is skeletal metastatic malignancy. In defective bone mineralization due to hyperparathyroidism or osteomalacia, a general increase in diphosphonate skeletal uptake is detected more frequently than radiographic abnormalities. However, normal skeletal images do not rule out metabolic bone disease. Biochemical testing is more reliable in detecting primary hyperparathyroidism. On the other hand, in renal osteodystrophy, biochemical abnormalities are variable and bone imaging is helpful in assessing the severity of skeletal involvement, but not its etiology. Many methods of quantitating the kinetics of Tc-99m diphosphonates have been explored, such as plasma clearance, bone-to-soft-tissue ratios, 24-hour total body retention and 24-hour urinary excretion. None of these have been widely accepted. The value of bone imaging is established in other systemic diseases, most notably in Paget's disease, hypertrophic pulmonary osteoarthropathy, sickle cell disease, fibrous dysplasia, and sympathetic dystrophy.
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PMID:Radionuclide imaging in metabolic and systemic skeletal diseases. 331 47

Heart and heart-lung transplant recipients at Stanford (Calif) University Medical Center were routinely prescribed long-term calcium carbonate antacid therapy to aid in the prevention of peptic ulcer disease and osteoporosis associated with glucocorticoid immunosuppressive therapy. Patients consumed 4 to more than 10 g/d of elemental calcium. Since calcium carbonate also provides the essential ingredients for the development of the milk-alkali syndrome, the laboratory flow sheets of 297 heart and heart-lung transplant recipients were reviewed to examine the incidence of hypercalcemia. Sixty-five patients developed significant hypercalcemia after transplantation. Thirty-one patients were alkalotic at the time of hypercalcemia; 37 had impairment in renal function. It is likely that most of these patients had the milk-alkali syndrome. While most patients became eucalcemic by discontinuing calcium carbonate therapy, intravenous hydration and forced diuresis were used to treat severe cases. It is possible that the incidence of the milk-alkali syndrome will increase with the current popularity of prescribing calcium carbonate for the prevention and treatment of osteoporosis.
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PMID:Milk-alkali syndrome in patients treated with calcium carbonate after cardiac transplantation. 353 84

The metabolic manifestations and operative findings in 10 patients with a diagnosis of parathyroid carcinoma were analyzed to determine whether they differ from those in patients with parathyroid adenomas and similar degrees of hypercalcemia. Two groups of patients with parathyroid adenomas were used for comparison. Group A consisted of eight patients with "atypical" benign adenomas (mean preoperative level of serum calcium: 13.4 mg/dl); group B consisted of 13 patients with benign typical adenomas--all with preoperative serum calcium levels greater than or equal to 13.0 mg/dl (mean: 14.2 mg/dl). The patients with carcinoma (mean preoperative level of serum calcium: 15.3 mg/dl) had a frequency of osteoporosis and osteitis fibrosa cystica (50%) comparable with that of group A (33%) and group B (62%). Seventy percent of the patients with carcinoma had renal disease (nephrolithiasis, nephrocalcinosis, or impaired renal function), whereas only 38% of group A and 15% of group B had similar disorders. The patients with carcinomas had the highest frequency of combined bone and renal disease (50% versus 14% in group A and 15% in group B). Anemia, peptic ulcer disease, and hypertension occurred with similar frequencies in the three groups. Three patients with recurrent parathyroid carcinoma died of profound hypercalcemia, renal failure, or cardiac arrhythmia. In general, although patients with parathyroid carcinomas have more profound metabolic abnormalities than do patients with primary hyperparathyroidism, the metabolic manifestations in patients with parathyroid carcinoma are comparable with those in patients with parathyroid adenomas and profound hypercalcemia. Furthermore atypical adenomas share many anatomic and histopathologic features with parathyroid carcinomas, and distinguishing between the two is sometimes possible only in cases of tumor recurrence.
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PMID:Parathyroid carcinoma versus parathyroid adenoma in patients with profound hypercalcemia. 358 61

Between July 1973 and December 1979, 1171 patients with metastatic breast cancer were treated with doxorubicin-containing chemotherapy. Of those patients, 195 had osseous metastases only. Upon initial diagnosis, 48% had osteolytic metastases; 13% had osteoblastic metastases; 38% had mixed metastases; and 1% had diffuse osteoporosis without any obvious bone destruction. The most common sites of involvement were the dorsal spine (62%), lumbosacral spine (72%), and pelvis (79%). Objective response to chemotherapy was observed in 59% of patients; complete responses were noted in 7%, and partial responses in 52%. The median survival was 28 months (range, 1-118 months). The median time lapse between the start of chemotherapy and disease progression was 14 months (range, 1-109 months). In 32 patients who responded to the treatment, chemotherapy was discontinued after 2 years, and their median duration of continued remission at 39 and 75 months after the completion of therapy. The incidence of pathological fractures was 57%; the most common sites were the spine, which sustained compression fractures, and the ribs. The incidences of hypercalcemia and spinal cord compression due to metastases were 19% and 10%, respectively.
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PMID:Clinical course of breast cancer patients with osseous metastasis treated with combination chemotherapy. 377 9

Depending on their symptomatology 152 cured (i.e., normocalcemic) patients with surgically proven primary hyperparathyroidism (pHPT) showed typical symptoms preoperatively. Besides hypercalcemia and elevated parathyroid hormone levels, 15 patients suffered only from hypertension and/or diffuse osteoporosis and/or complaints caused by the hypercalcemic syndrome (oligosymptomatic patients). Nine patients had no complaints (asymptomatic patients). The long-term clinical course of all patients was analyzed up to 22 years. Although the formation of urinary calculi was stopped in 94% of cases, a deterioration of renal function and hypertension was seen in symptomatic (12.5% and 9.2%, respectively) and oligosymptomatic patients (6.7% and 13.3%, respectively). Renal function and hypertension were unpredictable despite normalization of the hyperactive parathyroid metabolism and were of decisive prognostic significance; 6% died of acute or chronic renal failure, or of the consequences of hypertension. Multiple bone lesions, even large, healed functionally and were of no prognostic significance. In the majority of symptomatic patients gastrointestinal manifestations held postoperatively, but two patients died of acute pancreatitis without gastrointestinal complaints preoperatively. Almost all symptoms of the hypercalcemic syndrome disappeared immediately and permanently in symptomatic and oligosymptomatic patients. No deterioration of renal function and no elevation of blood pressure was observed in cured asymptomatic patients postoperatively. Immediate surgical treatment even in asymptomatic patients may have avoided complications of chronic renal failure or of hypertension. As soon as organic manifestations, even in a mild form, have been established, it seems impossible to predict the course and to prevent an unfavorable clinical outcome.
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PMID:[Clinical experiences following the surgical therapy of asymptomatic, oligosymptomatic and symptomatic parathyroid gland hyperfunction]. 378 42

The authors presented the results of a study of the indices of phosphorocalcium homeostasis, metabolism of osseous tissue and calcium regulating hormones in 44 patients with Icenko-Cushing's syndrome with regard to severity of disease and expression of osteoporosis. It was shown that disturbances of phosphorocalcium homeostasis and an increase in the level of the parathyroid hormone were characteristic for the active stage of Icenko-Cushing's disease and were most noticeable in a severe course of disease accompanied by sharply marked osteoporosis. Hypocalcemia, hypophosphatemia, hypercalciuria, a decrease in phosphate maximum resorption and an increase in AP activity in the blood serum were revealed in this form of disease. Patients with the average gravity of disease and weakly pronounced osteoporosis were characterized by hypercalcemia and an increase in calcium intestinal absorption. Patients with the active stage of hypercorticism were characterized by hypermagnesemia. Secondary hyperparathyrosis was found in 25% of patients with the active stage of Icenko-Cushing's disease.
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PMID:[Phosphorus-calcium metabolism and calcium-regulating hormones in endogenous hypercorticism]. 380 24


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