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)

The myopathy associated with vitamin D deficiency has not been well characterized, and it is not known if weakness is a result of a specific effect of vitamin D deficiency on skeletal muscle. Chicks were raised from hatching on a vitamin D-deficient diet, and by 3 wk of age were hypocalcemic and appeared weak. Tension generated by triceps surae during repetitive stimulation of posterior tibial nerve was significantly less than that developed by chicks given vitamin D(3) supplements (309 g tension/g wet weight of triceps surae, SD 60, for vitamin D-deficient chicks; 470, SD 77, for vitamin D(3)-treated chicks, P < 0.01). Histochemical and electron microscopic examination of skeletal muscles of these chicks showed no abnormalities, and there were no electrophysiologic evidences of motor nerve or neuromuscular junction dysfunction. The concentration of ATP in skeletal muscle of the vitamin D-deficient chicks (5.75 mumol/g wet weight, SD 0.17) was not significantly different from that in vitamin D-treated chicks (5.60, SD 0.50). There was no correlation between strength and serum calcium, serum inorganic phosphate, or skeletal muscle inorganic phosphate. Relaxation of tension after tetanic stimulation was slowed in the vitamin D-deficient chicks (20.6 ms, SD 1.7, vs. 15.4, SD 1.3, in vitamin D-treated chicks and 15.3, SD 1.0, in normal control chicks), and in vitro (45)Ca(++) transport by sarcoplasmic reticulum from the vitamin D-deficient chicks was reduced. Calcium content of mitochondria prepared from leg muscles of vitamin D-deficient chicks (24 nmol/mg mitochondrial protein, SD 6) was considerably lower than that of mitochondria from normal control chicks (45, SD 8) or from chicks treated with vitamin D for 2 wk or more (66-100, depending upon level and duration of therapy). Treatment of the vitamin D-deficient chicks from hatching with sufficient dietary calcium to produce hypercalcemia did not significantly raise skeletal muscle mitochondrial calcium content (31 nmol/mg mitochondrial protein, SD 7) and did not prevent weakness. These studies demonstrate objective weakness as a result of myopathy in vitamin D-deficient chicks, and provide evidence that vitamin D deficiency has effects on skeletal muscle calcium metabolism not secondary to altered plasma concentrations of calcium and phosphate.
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PMID:Skeletal muscle calcium metabolism and contractile force in vitamin D-deficient chicks. 22 25

Two groups of weanling pigs, injected with 45Ca, were fed diets containing optimal calcium and phosphorus, and vitamin D3 at 1320 IU/kg feed in the control group, and 825,000 IU/kg feed in the test group. The groups were further subdivided with 2 pigs in each subgroup, with survival times of 1, 2, 3, 4, 7, and 14 days. Pigs fed the high level of vitamin D3 lost weight and anorexia, weakness, rough hair coat and labored breathing were observed. Hypercalcemia began at 12 hours and progressed rapidly after 2 days. Radioisotope sutdies interpreted in the light of histopathologic findings indicated that bone was the primary source of increased plasma calcium. Calcium was released at a rapid rate into blood from prelabeled bone which was undergoing necrosis; it was also removed from blood and deposited into bone at a slower rate due to decreased apposition. Histopathologic examination of bones from test pigs showed regressive changes in the osteocytes, chondrocytes and osteoblasts which bean within 1 day of treatment and resulted in evidence osteopenia within 7 days. Arrested osteocytic osteolysis led to the appearance of cementing lines and to chondroid core retention. Further regressive changes in the osteocytes resulted in osteocytic death and osteonecrosis with subsequent osteoclasia and osteopenia. Retardation and arrest of cartilage maturation as well as osteoblastic deficiency contributed to the osteopenia. The osteopenia was further evidenced by decreased specific gravity and ash content per unit volume of humerus. The initial negative effect on the osteocytes, chondrocytes and osteoblasts is attributed to a direct toxic effect of excessive dietary vitamin D3 since hypoparathyroidism and hypercalcitoninism, which occur secondarily to hypercalcemia, could not account for the rapid appearance of this effect, nor are they known to induce osteocytic death. The release of bone calcium and the resulting hypercalcemia in vitamin D3 toxicosis is therefore due to a direct toxic effect of the vitamin, or its metabolites, on the osteocyte resulting in osteonecrosis. It is not due to increased resorption as has been reported previously from both in vivo and in vitro investigations. Degeneration, with subsequent inflammation, but without calcification, was observed in the kidneys and in the lungs. Epithelial cells, basement membranes, and smooth muscle were affected. This conclusively demonstrates that degeneration is the primary soft tissue lesion in vitamin D3 toxicosis, and that the subsequent calcification is therefore dystrophic. Degenerative changes occurred in the parathyroid glands within 1 day of treatment resulting in necrosis, inflammation and atrophy within 4 days. Relative fibrosis was seen as the parenchyma receded. The parathyroid gland changes were considered a direct effect of vitamin D3 toxicity since they occurred with only mild hypercalcemia and since necrosis of parathyroid cells has not been demonstrated with hypercalcemia either in vivo or in vitro.
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PMID:Vitamin D toxicity. Initial site and mode of action. 66 94

Primary hyperparathyroidism (PHPT) was the most likely diagnosis in 68 non-thiazide-treated patients with hypercalcaemia detected in a health screening. The group comprised 55 females and 13 males, with a mean age of 55.0 +/- 0.7 (S.E.M.) years. On a pair basis these patients (the observation group) were compared with a series of 68 age- and sex-matched normocalcaemic subjects (the control group) selected from the health screening register. Renal calcui and reduced creatinine clearance were encountered less frequently in the observation group than in many reports of hospitalized patients with PHPT. Compared with the control group, the observation group comprised a greater number of subjects with renal calculi (usually multiple and bilateral), constipation, mental depression and reduced creatinine clearance. The ECG Q-T interval was shorter in the observation group than in the control group. No differences were found with respect to the occurrence of gastritis and/or peptic ulcer, poly-dipsia, polyuria and general muscle weakness. On the basis of this and a previous study it was concluded that at least 3% of the 15903 subjects participating in the health screening suffered from "asymptomatic" hypercalcaemia and most probably from "asymptomatic" PHPT.
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PMID:Clinical and laboratory findings in subjects with hypercalcaemia. A study including cases with primary hyperparathyroidism detected in a health screening. 98 6

Thirteen muscle biopsy specimens (mainly the gluteus maximus) from 12 patients with laboratory confirmation of osteomalacia and proximal muscle weakness in 10 were examined by light and electron microscopy. Light microscopy revealed mild diffuse non-specific atrophy of the muscle fibres in 10 cases, severe generalised atrophy in one and patchy group atrophy in one. There was no myopathic change in specimens from cases with either a nutritional aetiology, or a mixed aetiology. The former, mostly women gave a history of severe chronic malnutrition often accompanied by repeated pregnancies and prolonged lactation; those with a mixed aetiology gave, in addition, evidence of a metabolic or endocrine disorder such as hyperparathyroidism, hyperthyroidism, uraemia, or treatment with anti-epileptic drugs or were of uncertain origin. Electron-microscope examination of muscle from the nutritional group showed atrophic changes in the fibres, such as loss of myofibrils, prominence of mitochondria and glycogen, loosening and folding of the basement-membrane but good preservation of the remaining myofibrils. In contrast muscle from cases of mixed aetiology showed, in addition to the atrophic features, clear degenerative changes in the myofibrils and the mitochondria, accumulation of amorphous material at the site of myofibrillar loss and of lipofuscin in muscle fibres, vascular endothelium and satellite cells. The earliest degenerative change was in the "I" band, involving actin filaments and "Z" line. The triads were generally preserved but the sarcoplasmic reticulum appeared affected in a patient with tetany and severe mitochondrial degeneration. In a patient with thyrotoxicosis, proliferation of central nuclei, "Z" line streaming and formation of "T" tubular aggregates were seen. In one patient with hyperparathyroidism and hypercalcaemia, severe myofibrillar degeneration and mitochondria showing osmiophilic deposits, possibly of calcium phosphate, were encountered. It is concluded: (1) that all osteomalacic muscle weakness is not myopathic but a non-specific atrophy occurring probably on the basis of disuse and malnutrition, and (2) patients with an added metabolic or endocrinological disorder show in addition to the atrophy, degenerative changes in the muscle fibre and its sub-cellular components consistent with myopathy, and these patients should be clearly distinguished from those with a background of malnutrition only.
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PMID:Nature of muscular change in osteomalacia: light- and electron-microscope observations. 121 91

We report the case of a 33-year-old woman who was operated on with the diagnosis of primary hyperparathyroidism (PHP) in 1986. She had bone disease and slight hypercalcemia. Two parathyroid glands were removed with a lack of clinical improvement. Subsequently, the serum calcium levels were normal with occasional slight increases. Depressed phosphorus values and elevated alkaline phosphatases and PTH levels were also present, associated with severe bone involvement and muscular weakness. A second cervical exploration performed in 1989 disclosed only a normal parathyroid gland, which was not removed. In 1990, a thoracic CT scan showed the presence of a 1 cm mediastinal nodule close to the great vessels. A thoracotomy was performed to remove this nodule, which proved to be a parathyroid adenoma. After surgery, the patient presented with a "hungry bone" syndrome, characterized by very low levels of calcium, phosphorus and magnesium, which required enteral and parenteral calcium and magnesium supplements, plus dihydroxyvitamin D. The association of normocalcemia and intermittent hypercalcemia with severe bone disease is very rare, as is the presence of a mediastinal adenoma. This could explain the difficulty in the diagnosis in this case.
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PMID:[Primary hyperparathyroidism caused by a mediastinal adenoma with intermittent hypercalcemia and severe bone disease]. 134 71

We report a case of IgE myeloma in a 78-year-old woman who presented with bone pain in the shoulder and hip and progressive weakness. Except for hypercalcemia, routine chemistry values were within normal limits. Hemoglobin was decreased and the leukocyte count slightly increased. Plasma cells were not observed in the peripheral blood. Serum protein electrophoresis showed a monoclonal protein in the beta-globulin fraction. Immunofixation confirmed the presence of an IgE kappa monoclonal protein. A bone marrow biopsy revealed an interstitial and nodular infiltration of abnormal plasma cells comprising 60% of nucleated cells present. Skeletal roentgenograms and bone scans of this patient showed osteolytic lesions and osteopenia of the thoracic and lumbar spine and osteolytic destruction of the right half of the sacrum. Flow-cytometric analysis of mononuclear cells isolated from peripheral blood showed that 15% of the lymphocytes bound IgE. Using cell-surface markers, we identified 45% of the IgE-positive cells as natural killer cells. Similar results have been found in other diseases marked by increased IgE. The clinical, radiological, and laboratory findings for this patient are compared with previously reported cases of IgE and other types of myeloma.
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PMID:A new case of IgE myeloma. 142 32

We describe a neonate with distal renal tubular acidosis with secondary hyperparathyroidism manifesting as hyperchloraemia, hypercalcaemia, elevated serum parathyroid hormone (PTH) and life-threatening metabolic acidosis. He exhibited general weakness, tachypnoea, dry skin and weight loss. Urinary excretion of titratable acid and ammonium was decreased. Daily alkali (2.5 mEq/kg body weight) was required to maintain a normal plasma bicarbonate (HCO3-). With alkali therapy, the fractional excretion of HCO3- was below 5%. Serum calcium and PTH were restored to normal promptly on initiation of alkali therapy. After 5 months of alkali therapy, normal growth and urine acidifying ability were restored and alkali therapy was discontinued. The acidification defect in this patient was transient. We consider this patient to be consistent with Lightwood's syndrome of "transient infantile renal tubular acidosis".
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PMID:Transient neonatal distal renal tubular acidosis with secondary hyperparathyroidism. 161 37

In 23 unselected cases of primary hyperparathyroidism (pHPT), muscle strength, morphology and enzymatic activities were studied and electromyography (EMG) performed before and 6 months after surgical treatment. Hypercalcemia was mostly mild or moderate. Nine women undergoing surgery for benign thyroid conditions served as controls regarding muscle strength, while muscle morphologic and enzymatic data were compared with findings in healthy persons of similar age. Only three pHPT patients reported muscle weakness preoperatively, and two were subjectively improved after surgery. Muscle strength did not differ significantly before or after operation between patients and controls: After surgery both groups showed increased isokinetic muscle strength at higher angular velocities. Nor did muscle morphology differ between pHPT patients and controls. No conclusive EMG changes were found before or after surgery for pHPT but postoperatively the pHPT patients showed significant increase in glycolytic but not oxidative muscle enzymes, possibly reflecting early effect of pHPT on especially type II fibers, which previously were shown to be most extensively involved in pHPT. Otherwise no measurable negative effects of mild or moderate pHPT were found on muscle strength or function.
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PMID:Muscle structure and function before and after surgery for primary hyperparathyroidism. 167 75

Several recent articles question whether patients with asymptomatic hyperparathyroidism and minimal hypercalcemia should be treated by parathyroidectomy. We therefore reviewed our experience in 103 consecutive patients with primary hyperparathyroidism who were treated by parathyroidectomy to determine, first, how many of these patients had asymptomatic or symptomatic hyperparathyroidism, and second, did these patients benefit from parathyroidectomy? We also analyzed the safety of parathyroidectomy in 426 consecutive patients, including 79 who required reoperation for hyperparathyroidism, specifically looking for complications and the outcome of these procedures. Our study documents the following: (1) only 2 of 103 (2%) patients referred for parathyroidectomy had "true" asymptomatic hyperparathyroidism; (2) only symptoms of fatigue, bone pain, and weight loss correlated with the degree of hypercalcemia, whereas muscular weakness, psychiatric symptoms, nocturia, polyuria, recent memory loss, constipation, and nephrolithiasis did not; (3) only 1 of 15 patients who were referred as asymptomatic were truly asymptomatic after more thorough questioning, and all 14 improved following parathyroidectomy; (4) 81% of the patients who were referred with symptoms improved following parathyroidectomy; and (5) permanent complications occurred in only 4 patients. All but 1 had reoperations for persistent or recurrent hyperparathyroidism (3 vocal cord paralyses and 1 hypoparathyroidism requiring autotransplantation of cryopreserved parathyroid tissue). There was 1 death of an 84-year-old woman with hypercalcemic crisis. Thus, most patients with hyperparathyroidism are symptomatic and benefit symptomatically and metabolically from parathyroidectomy, which is a safe operation.
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PMID:Diagnosis and management of asymptomatic hyperparathyroidism: safety, efficacy, and deficiencies in our knowledge. 176 65

Primary hyperparathyroidism was thought 30 years ago to be a rare disease, and the diagnosis was most often made in patients presenting with either bone disease or kidney stones. Today the minority of patients with hyperparathyroidism present with such symptoms, a fact accounted for by the introduction into general medical practice three decades ago of laboratory technology for efficiently determining the serum concentrations of various blood minerals, including calcium. Hypercalcemia was detected more frequently, and it was realized that most patients with hyperparathyroidism either had minor symptoms, such as constipation, polyuria, tiredness, and muscle weakness, or they were "asymptomatic" and indistinguishable from normal subjects. It was thought that primary hyperparathyroidism was a progressive disease and that sooner or later all patients would become symptomatic and require parathyroidectomy. Since this operation was curative in a high percentage of cases, it was recommended for virtually all patients once the diagnosis was established. In this contribution the long-term benefits of parathyroidectomy in patients with and without symptoms from primary hyperparathyroidism are reviewed. It is concluded that a multicenter prospective randomized trial is needed to resolve the indications for operative and nonoperative management of patients with this disease.
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PMID:Surgical therapy of patients with primary hyperparathyroidism: long-term benefits. 176 66


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