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Query: UMLS:C0020437 (hypercalcemia)
 10,293 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 7-year-old boy developed acute, severe hypercalcaemia following the partial excision of a cerebellar medulloblastoma. The serum calcium level was extremely high (19.8 mg/100 ml), but a skeletal survey revealed no apparent bone metastatic lesions; such lesions were only detected by X-ray 3 weeks after the onset of hypercalcaemia. Hypercalcaemia was promptly resolved by intravenous mithramycin administration, before which the serum parathyroid hormone level, 1,25-(OH)2-vitamin D level and the nephrogenous cyclic AMP level were low. However, the relation between serum calcium levels and urinary calcium excretions indicated that renal calcium reabsorption was increased in association with hypercalcaemia, suggesting that a parathyroid hormone-like effect was operative on the renal tubules. It is possible that a combination of increased bone resorption by metastatic tumour cells and renal tubular handling of calcium presumably mediated by tumour-produced humoral factors was responsible for the acute development of severe hypercalcaemia in this patient with medulloblastoma.
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PMID:Hypercalcaemia in cerebellar medulloblastoma: pathogenesis of solid tumour-associated hypercalcaemia. 365 40

A 64 year old woman had been on lithium carbonate for 12 years for manico-depressive psychosis. Mild asthenia leads to the diagnosis of primary hyperparathyroidism based on the findings of hypercalcemia up to 2.85 mmol/l inappropriate levels of parathormone and a non-suppressive rise of nephrogenic cyclic AMP. These symptoms were not relieved by removal of a chief cell adenoma of the left inferior parathyroid; surgical reexploration leads to the removal of an adenoma in a high, ectopic situation. Further venous samplings were collected during cervico mediastinal phlebography because of persistent hypercalcemia: parathormone levels were high in a thymic vein and a new cervicotomy revealed a fifth gland with an adenoma in the high mediastinum. After removal of the third adenoma, the patient became hypocalcemic. Lithium was not discontinued according to the patient's wishes. Eighteen months later she was well and normocalcemic on alfacalcidol therapy. Multiple adenomas of the parathyroids are rare (1.7 p. 100 to 5 p. 100) and the recurrence of an adenoma on a supernumerary gland is exceptional. Eighteen clinical cases of primary hyperparathyroidism under lithium therapy have been reported, but mild asymptomatic hypercalcemia with inappropriate increased parathormone levels seems to be more common. Duration of treatment is very variable: 1 day to 12 years, and serum calcium levels or up to 3.9 mmol have been observed. Ten patients underwent cervicotomy with removal of an adenoma 6 of them remaining under treatment, with 2 recurrences in our case. Five of the 8 non-operated patients remained on lithium therapy and showed mild hypercalcemia.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Multiple hypersecreting lesions of the parathyroid glands during treatment with lithium]. 371 17

Hypercalcemia was associated with osteolytic bone lesions in a 60-year-old woman with chronic myelogenous leukemia in the accelerated phase. Using highly specific antisera to parathyroid hormone, radioimmunoassays disclosed elevated levels of carboxyl-terminal (53-84) and intermediate (44-68) fragments. In addition, concomitant variations of serum calcium level and leukocyte counts, increased urinary c-AMP excretion, morphological integrity of parathyroid glands, and absence of bone resorbing activity in myeloblast culture supernatants are consistent with the hypothesis that the humoral hypercalcemia was due to the excessive production of PTH. This production may have been ectopic, although no PTH secretion was demonstrated in myeloblast culture supernatants.
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PMID:Hypercalcemia in chronic myelogenous leukemia: evidence for excessive parathyroid hormone secretion. 386 73

Hypocalcemia is a frequent feature of hypomagnesemia in man and several other species. To elucidate the cause of this hypocalcemia, we have studied a child with primary hypomagnesemia and secondary hypocalcemia during magnesium supplementation when he was normomagnesemic and normocalcemic and after magnesium restriction for 16 days when he quickly became hypomagnesemic (0.5 meq/liter) and hypocalcemic (3.4 meq/liter) and had positive Chvostek's and Trousseau's signs. Whether in the normomagnesemic or hypomagnesemic state, intravenous bovine parathyroid extract (PTE) 8 U. S. P. U/kg promptly caused transient increases in the urinary phosphate excretion, renal phosphate clearance and cyclic AMP excretion. The magnitudes of these responses were similar in the two states, and similar to those observed in a hypoparathyroid patient. When the patient was hypomagnesemic and hypocalcemic, intramuscular PTE, 8 U/kg at 8-h intervals for four doses promptly caused hypercalcemia. The findings indicate that the end-organs were responsive to parathyroid hormone. The concentrations of serum parathyroid hormone (PTH) were normal in the normomagnesemic state ranging from 0.15 ng/ml to 0.40 ng/ml. Serum PTH did not increase in the hypomagnesemic state in spite of hypocalcemia. Indeed, PTH became unmeasurable in four consecutive samples at the end of the period of magnesium restriction. The concentrations of serum calcitonin remained unmeasurable (< 0.10 ng/ml) throughout the study, implying that excess calcitonin was not the cause of hypocalcemia in magnesium depletion. The findings in this study support our thesis that magnesium depletion causes impaired synthesis or secretion of parathyroid hormone. This impairment would account for the hypocalcemia observed in the hypomagnesemic state.
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PMID:Pathogenesis of hypocalcemia in primary hypomagnesemia: normal end-organ responsiveness to parathyroid hormone, impaired parathyroid gland function. 434 1

The causes for the hypercalciuria and diagnostic criteria for the various forms of hypercalciuria were sought in 56 patients with hypercalcemia or nephrolithiasis (Ca stones), by a careful assessment of parathyroid function and calcium metabolism. A study protocol for the evaluation of hypercalciuria, based on a constant liquid synthetic diet, was developed. In 26 cases of primary hyperparathyroidism, characteristic features were: hypercalcemia, high urinary cyclic AMP (cAMP, 8.58+/-3.63 SD mumol/g creatinine; normal, 4.02+/-0.70 mumol/g creatinine), high immunoreactive serum parathyroid hormone (PTH), hypercalciuria, the urinary Ca exceeding absorbed Ca from intestinal tract (Ca(A)), high fasting urinary Ca (0.2 mg/mg creatinine or greater), and low bone density by (125)I photon absorption. The results suggest that hypercalciuria is partly secondary to an excessive skeletal resorption (resorptive hypercalciuria). The 22 cases with renal stones had normocalcemia, hypercalciuria, intestinal hyperabsorption of calcium, normal or low serum PTH and urinary cAMP, normal fasting urinary Ca, and normal bone density. Since their Ca(A) exceeded urinary Ca, the hypercalciuria probably resulted from an intestinal hyperabsorption of Ca (absorptive hypercalciuria). The primacy of intestinal Ca hyperabsorption was confirmed by responses to Ca load and deprivation under a metabolic dietary regimen. During a Ca load of 1,700 mg/day, there was an exaggerated increase in the renal excretion of Ca and a suppression of cAMP excretion. The urinary Ca of 453+/-154 SD mg/day was significantly higher than the control group's 211+/-42 mg/day. The urinary cAMP of 2.26+/-0.56 mumol/g creatinine was significantly lower than in the control group. In contrast, when the intestinal absorption of calcium was limited by cellulose phosphate, the hypercalciuria was corrected and the suppressed renal excretion of cAMP returned towards normal. Two cases with renal stones had normocalcemia, hypercalciuria, and high urinary cAMP or serum PTH. Since Ca(A) was less than urinary Ca, the hypercalciuria may have been secondary to an impaired renal tubular reabsorption of Ca (renal hypercalciuria). Six cases with renal stones had normal values of serum Ca, urinary Ca, urinary cAMP, and serum PTH (normocalciuric nephrolithiasis). Their Ca(A) exceeded urinary Ca, and fasting urinary Ca and bone density were normal. The results support the proposed mechanisms for the hypercalciuria and provide reliable diagnostic criteria for the various forms of hypercalciuria.
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PMID:The hypercalciurias. Causes, parathyroid functions, and diagnostic criteria. 436 91

A possible association between the impairment of urinary concentrating ability and an impairment of the vasopressin-dependent cyclic AMP system in hypercalcemia was investigated in rat kidneys both in vivo and in vitro. The increases of urinary osmolality and negative free water clearance and the increase of urinary cyclic AMP excretion by vasopressin injection were significantly less in the hypercalcemic rats than in the control rats. The increase of cyclic AMP concentration by vasopressin in renal medullary tissue was significantly less in the slices obtained from the hypercalcem'c rats than in those obtained from the control rats. The activation of adenylate cyclase by vasopressin was significantly less in the group with an increased concentration of calcium in media than the control group, but phosphodiesterase activity was not affected by calcium concentration in the media. These data suggest that the impaired urinary concentrating ability in hypercalcemic kidneys is due at least in part to the direct inhibitory effect of calcium on the vasopressin-dependent cyclic AMP system at the level of adenylate cyclase in renal medulla.
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PMID:Pathogenic role of cyclic AMP in the impairment of urinary concentrating ability in acute hypercalcemia. 437 61

There is an increasing use and variety of beta-adrenoceptor blocking agents (beta-blockers) available for the treatment of hyperthyroidism. Recent comparative studies suggest that atenolol (200mg daily), metoprolol (200mg daily); acebutolol (400mg daily), oxprenolol ( 160mg daily), nadolol ( 80mg daily) and timolol (20mg daily) produce a beneficial clinical response equal to that seen with propranolol ( 160mg daily). Most beta-blockers reduce resting heart rate by approximately 25 to 30 beats/min, although a lesser reduction is seen with those possessing intrinsic sympathomimetic activity such as oxprenolol and pindolol. While earlier studies employing large doses of intravenous propranolol concluded that beta-blockade reduced myocardial contractility, more recent non-invasive studies suggest that the predominant cardiac effect is on heart rate. In patients with cardiac failure, beta-blockers may, however, produce a profound fall in cardiac output. Nevertheless, in combination with digoxin they may be useful in controlling the atrial fibrillation of thyrocardiac disease. beta-Blockers improve nervousness and tremor (although to a lesser extent with cardioselective agents) and severe myopathy, and they also reduce the frequency of paralysis in patients with thyrotoxic periodic paralysis. There is often subjective improvement in sweating but usually no major effect on eye signs. Recent studies show a 10% reduction in oxygen consumption/basal metabolic rate with long term oral use of selective or nonselective beta-blockers. In addition, many agents (propranolol, metoprolol, nadolol and sotalol but not acebutolol, atenolol or oxprenolol) reduce circulating tri-iodothyronine (T3) concentration by between 10 and 40%, although the clinical significance of this effect (if any) is not established. beta-Blockers may also have endocrinological effects on gastrin, cyclic AMP, catecholamines and other hormone levels. Given in adequate dosage, propranolol has been shown to control thyrotoxic hypercalcaemia. Minor side effects (nausea, headaches, tiredness, etc.) are quite common but overall beta-blockers are well tolerated by the thyrotoxic patient. The major use of these drugs is in symptomatic control while awaiting definitive diagnosis or treatment. As an adjunct to antithyroid drugs or radioactive iodine, beta-blockers will produce a satisfactory clinical response in the weeks to months before these forms of therapy produce a euthyroid state. beta-Blockers are more convenient than antithyroid drugs in the control of patients receiving therapeutic radioiodine, in that continuous therapy and assessment of biochemical response is possible.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Use of beta-adrenoceptor blocking drugs in hyperthyroidism. 614 1

The availability of accurate and inexpensive methods for measuring serum calcium levels has resulted in a rapid increase in the number of diagnoses of primary hyperparathyroidism, notably in its asymptomatic hypercalcemic forms. In addition, the development of a radioimmunoassay of the parathyroid hormone and, more recently, measurements of nephrogenous cyclic AMP during fasting and after calcium loading have led to the recognition of clinical variants of the disease, such as intermittent or borderline hypercalcemia and pure hypercalciuria with normal calcemia. The degree of hypercalcemia in stable primary hyperparathyroidism depends on renal tubular reabsorption of calcium rather than on bone resorption. The poor correlation observed between calcium tubular reabsorption rate and magnitude of parathyroid hormone hypersecretion suggests that as yet undetermined factors interfere with the effects of parathyroid hormone on renal tubules and probably account for the fluctuations in calcemia reported during serial determinations in patients. The sigmoid relationship between parathyroid hormone release and extracellular calcium concentrations has been analyzed from recent in vitro studies with dispersed parathyroid cells. In primary hyperplasia of the parathyroid glands hypersecretion of parathyroid hormone seems to depend principally upon the increase in tissue mass with normal sensitivity to calcium at cellular levels, whereas in adenoma the primary abnormality responsible for hypersecretion of parathyroid hormone would be an alteration in cell sensitivity to calcium, as indicated by an elevated "set point". Finally, while complicated primary hyperthyroidism requires surgery, our limited knowledge of the natural history of asymptomatic forms makes it impossible to decide which of these patients will ultimately need to be operated upon.
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PMID:[Present status of primary hyperparathyroidism]. 623 8

Ten patients with subtle primary hyperparathyroidism and intermittent hypercalcaemia were followed serially for periods of 2--18 months (mean 10 months). Fasting serum calcium was elevated (greater than 10.6 mg/dl) in only 20% of determinations and fluctuated widely (9.1--11.2 mg/dl), yet the patients displayed a continuous, rather than episodic, basic disease process as defined by increases in nephrogenous cyclic AMP and serum iPTH. Identical findings were noted in short-term (2--3 successive days) studies in twelve patients. In response to a 1000 mg oral calcium tolerance test, twelve patients with primary hyperparathyroidism and intermittent hypercalcaemia (basal serum calcium 10.2 +/- 0.2 mg/dl, mean +/- SD) displayed: (1) hyperabsorption of calcium (mean calciuric response twice normal); (2) induced-hypercalcaemia (mean serum calcium 11.4 mg/dl, with a mean increase of 1.2 mg/dl versus 0.2 mg/cl in normal subjects); and (3) abnormal parathyroid suppressibility (nephrogenous cyclic AMP 2.66 +/- 0.57 nmol/100 ml GF versus 0.95 +/- 0.40 nmol/100 ml GF in normal subjects, mean +/- SD). The patients demonstrated striking hypercalciuria (452 +/- 123 mg/24 h) on a 1000 mg metabolic calcium diet. Serum levels of 1,25(OH)2D3, measured in ten patients, were markedly elevated at 90 +/- 20 pg/ml (mean +/- SD), and there was a strong positive correlation between the values for 1,25(OH)2D3 and the calciuric response to the calcium tolerance test (r = 0.75, P less than 0.001). These results (1) indicate that the calcium tolerance test is a simple and reliable technique for diagnosis of patients with primary hyperparathyroidism and intermittent hypercalcaemia, and (2) emphasize the important pathophysiologic features of this subtle clinical variant of primary hyperparathyroidism.
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PMID:Primary hyperparathyroidism with intermittent hypercalcaemia: serial observations and simple diagnosis by means of an oral calcium tolerance test. 624 72

In 50 consecutive patients with cancer-associated hypercalcemia, we measured nephrogenous cyclic AMP, tubular phosphorus threshold, fasting calcium excretion, plasma 1,25-dihydroxyvitamin D, and immunoreactive parathyroid hormone as determined by four region-specific antiserums. Nephrogenous cyclic AMP excretion was elevated in 41 patients and suppressed in nine (means, 5.85 vs. 0.51 nmol per 100 ml of glomerular filtrate). There was no overlap between these groups. When compared with 15 patients with primary hyperparathyroidism, the group with increased cyclic AMP excretion had similar reductions in tubular phosphorus threshold; higher fasting calcium excretion (means, 0.66 vs. 0.25 mg per 100 ml of glomerular filtrate, P < 0.01); marked reductions in 1,25-dihydroxyvitamin D (means, 20 vs. 83 pg per milliliter, P < 0.001); and lower levels of immunoreactive parathyroid hormone in all four assays. The data suggest that elevated excretion of nephrogenous cyclic AMP may be a useful marker of humorally mediated cancer-associated hypercalcemia, that this type of hypercalcemia is common, that the humoral factor responsible for this syndrome is not native 1-84 parathyroid hormone, and that the various subtypes of cancer-associated hypercalcemia are biochemically distinguishable from primary hyperparathyroidism.
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PMID:Biochemical evaluation of patients with cancer-associated hypercalcemia: evidence for humoral and nonhumoral groups. 625 85


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