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

After confirming hypercalcemia by 3 successive measurements of the total plasma calcium corrected for a plasma protein concentration of 72 g/l, which excludes spurious hypercalcemia due to dehydration, the physician orientates the aetiological diagnosis bearing in mind that primary hyperparathyroidism PHPT is the cause of 85 p. 100 of all asymptomatic forms of hypercalcaemia whilst overt or occult malignancy is the main cause (60 p. 100) of symptomatic forms of hypercalcaemia with PHPT responsible for 20 p. 100 of cases. Other causes, including drug toxicity with Vit D, calcium, Vit A, lithium, thiazide and aluminium hydroxide, sarcoidosis, hyperthyroidism, Addison's disease, pheochromocytoma and familial endocrine disorders are much rarer. Nevertheless, these rarer causes must be excluded on the clinical history and examination followed by radiological (chest X ray, plain abdomen X ray, bone X rays) and simple biological tests. The latter and/or scans tests should also help in a rapid diagnosis of metastatic carcinoma and multiple myeloma, so that the major diagnostic problem is to distinguish primary HPT from occult malignancy. This problem is greatly facilitated by reliable assays of C terminal or medium PTH rather than renal CAMP which is increased in 80 p. 100 of occult malignancies. When PTH assays is unavailable or unreliable Dent's hydrocortisone suppression test may be useful as a fall in'serum calcium is associated with occult malignancy in 70 p. 100 of cases and non-suppression is associated with PHPT in 91 p. 100 of cases. Discriminant analysis of the usual biochemical parameters may be helpful in this differential diagnosis and is accurate in about 90 p. 100 of cases. However, the association of PHPT and malignancy is also possible and not fortuitous.
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PMID:[Stages of the etiological diagnosis of hypercalcemia]. 389 Jun 61

We have purified peptides with PTH-like bioactivity from a rat Leydig cell tumor (H-500) and a human squamous cell carcinoma, both associated with a syndrome of humor-induced hypercalcemia. Tumor extracts were shown to be active in an in vitro renal cytochemical bioassay and in an in vitro osteosarcoma cell (UMR 108) adenylate cyclase assay; activity in both assays could be reduced by the PTH antagonist [norleucine-8,18,tyrosine-34]bovine PTH-(3-34)-amide. Partially purified extracts of both tumors and of rat tumor-conditioned culture medium were active in vivo in thyroparathyroidectomized rats in preventing hypocalcemia and increasing fractional phosphorus excretion and cAMP excretion. Ion exchange chromatography demonstrated that active peptides were basic in character. Employing reverse phase HPLC and gel permeation HPLC, active peptides of approximately 9,000 and 9,500 daltons were purified from extracts of the human and rat tumors, respectively, which had similar but not identical compositions. Two additional bioactive peptides were detected in rat tumor extract, and the more active had a mol wt of approximately 28,000. The results demonstrate that peptides that mimic PTH in a variety of in vivo and in vitro bioassays can be extracted from malignancies associated with hypercalcemia, that multiple molecular species may be detected in tumors that demonstrate PTH-like activity, and that at least one of these peptides may be similar in two tumors of highly divergent cell and species origin.
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PMID:Purification of peptides with parathyroid hormone-like bioactivity from human and rat malignancies associated with hypercalcemia. 394 72

Urinary excretion of cyclic adenosine 3',5'-monophosphate (3',5'-AMP) was tested in normal subjects and patients with pseudohypoparathyroidism, idiopathic hypoparathyroidism, surgical hypoparathyroidism, and pseudopseudohypoparathyroidism under basal conditions and after a 15 min infusion of purified parathyroid hormone. Basal excretion of the nucleotide was less than normal in the patients with hypocalcemic disorders and greater than normal in pseudopseudohypoparathyroidism. Parathyroid hormone caused a marked increase in excretion of 3',5'-AMP in all subjects except those with pseudohypoparathyroidism; nine patients with this disorder did not respond to the hormone and four showed a markedly deficient response. Radioimmunoassay showed that parathyroid hormone circulated in increased amounts in plasma from patients with pseudohypoparathyroidism and became undetectable when serum calcium was increased above 12 mg/100 ml. Suppression of parathyroid hormone secretion by induction of hypercalcemia did not alter the deficient response to exogenous hormone. The results indicate that: (a) parathyroid hormone circulates in abnormally high concentrations in pseudohypoparathyroidism and secretion of the hormone responds normally to physiological control by calcium; (b) testing urinary excretion of 3',5'-AMP in response to infusion of purified parathyroid hormone appears to be an accurate and sensitive index for establishing the diagnosis of pseudohypoparathyroidism; and (c) the metabolic defect of the disorder can be accounted for by a lack of or defective form of parathyroid hormone-sensitive adenyl cyclase in bone and kidney.
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PMID:Pseudohypoparathyroidism: defective excretion of 3',5'-AMP in response to parathyroid hormone. 430 2

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

We studied 5 patients with immobilisation hypercalcemia. Plasma calcium was 3.28 +/- (SD) 0.26 mmol/l. Plasma parathyroid hormone (PTH) level was elevated in 3 patients and inappropriately detectable in 1. Nephrogenous cAMP, measured in 3 patients, was low-normal in 1 who had a normal PTH and zero in 2 who had elevated PTH. Quantitative bone histology was performed in 3 patients. 1 had evidence of increased resorption (osteoclast count 7.1/mm2 section area, normal 1.0 +/- 0.5) and had a high-normal bone formation rate. Another had a normal osteoclast count but no evidence of bone formation. The third had normal bone histology. We conclude that (a) the PTH appears to be biologically inactive and its elevation may be due, in some patients, to renal retention of carboxyterminal fragments; (b) the histologic pattern in bone is variable and not predictable from the duration of illness; (c) the mechanism by which immobilisation induces these changes is obscure, and (d) careful clinical assessment may be necessary to avoid misdiagnosing the condition as primary hyperparathyroidism.
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PMID:Immobilisation hypercalcemia. 608 2

(Asu) E-CT is a deaminodicarba-analog of the synthetic eel-calcitonin (E-CT) that shows specific activity and the potency reasonably high in comparison with that of the most potent natural hormone. The structure of its molecule indicates that the disulphide bond in calcitonins is not essential for the biological activity but only for the maintenance of the specific conformation by forming an intramolecular bridge. The instability of calcitonins should mainly be attributed to the presence of the disulfide bond and (Asu)E-CT proved to be more stable "in vitro" than native calcitonins. The more prolonged hypocalcemic effect of E-CT and its aminosuberic analog (Asu)E-CT has been accounted for to a greater stability of and persistence at the receptor site. (Asu) E-CT has been largely studied in Japan on experimental animals and successfully used in the treatment of hypercalcemia in man. On the contrary investigations on human administration of this analog are very scarce. The present paper reports studies carried out in normal subjects and Paget's disease patients to investigate the effects of (Asu)E-CT in man in comparison with the effects of synthetic human calcitonin (H-CT) and synthetic salmon calcitonin (S-CT). Two different experimental procedures have been used: 1) rapid intravenous injection of (Asu)E-CT (80 MRC. U.) or respectively of H-CT and S-CT (100 MRC. U.) in 15 subjects (7 normals and 8 with Paget's disease); 2) slow 7 days continuous subcutaneous infusion of similar daily amounts of (Asu)E-CT, H-CT and S-CT administered by a microjet pump device in 21 subjects (7 normals and 14 with Paget's disease). The intravenous administration of (Asu)E-CT induced a rapid and persistent decrease in total plasma calcium, ionized calcium and plasma phosphate that was more evident in Paget's disease patients than in normal subjects. No clearly cut differences have been observed with the hypocalcemic and hypophosphatemic effect of H-CT and S-CT administered intravenously; nevertheless the hypocalcemic effect proved to be more persistent in Paget's disease patients treated with (Asu)E-CT. After intravenous infusion of (Asu)E-CT the plasma level of cAMP rose more evidently in pagetic than in normal subjects but the rise was lower than in H-CT and S-CT treated subjects.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Asu(1,7)E-CT, an analog of eel calcitonin. A comparative study in man with reference to other synthetic calcitonins]. 608 15

The effects of isoproterenol (ISO, 1 X 10(-7) M) and phenylephrine (beta-PHEN, 5 X 10(-5) M, in the presence of 5 X 10(-6) M phentolamine) as well as the effect of hypercalcemia (5.7 X 10(-3) M instead of 1.9 X 10(-3) M) on the kinetics of changes in developed tension (DT) and its second derivative (T") and on cAMP level and 45Ca uptake were studied in spontaneously beating rat atria. Both the effects of ISO and the beta-adrenergic effect of PHEN on amplitude were equipotent 15 and 60 sec after administration. However, the ISO response developed faster, and the amplitude at 30 sec was significantly higher in the ISO than in the PHEN response. The effects of ISO on the ratio of the amplitudes of the first maximum and the minimum of T" (T"max/T"min) as well as on the duration of the contraction-relaxation cycle (CRC) were biphasic. At 15 sec, it first produced increases, and subsequently, 60 sec after the drug, these parameters decreased below the control. beta-Phenylephrine produced a similar biphasic response in the ratio T"max/T"min, but the duration of CRC appeared only to decrease 60 sec after the drug. The durations of the contraction phases of T" were reduced both by ISO (30 and 60 sec) and beta-PHEN (60 sec) after administration. All of the effects of beta-PHEN on T" were weaker than those induced by ISO. Furthermore, the ability of PHEN to stimulate the formation of cAMP was also poorer. The inhibition of phosphodiesterase by methylisobutylxanthine enhanced, dose dependently, the increase in the relaxing components of CRC. However, the amplitude response of ISO was antagonized by this drug. The time course effects of ISO on the amplitude and cAMP were parallel. beta-Phenylephrine stimulated first contractility and much later an increase in cAMP. Uptake of 45Ca was stimulated equally by ISO and beta-PHEN. Hypercalcemia produced increases in amplitude, in the ratio T"max/T"min, and in the duration of CRC but no change in the level of cAMP. The data suggest that the beta-adrenergic response is at the outset qualitatively similar to the response of hypercalcemia and that the typical changes in CRC for beta stimulation take place only secondly. Thus, even though cAMP is involved in beta-adrenergic stimulation, it may not be the main cause of positive inotropism. The qualitative changes in CRC, i.e., the increase in the relaxing components and the decrease in time to peak tension, could be responsible for the faster increase in amplitude to the steady-state level.
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PMID:Cyclic AMP-dependent and -independent effects of beta-adrenergic stimulation on the contraction-relaxation cycle of spontaneously beating rat atria. 618 64

We investigated cAMP metabolism during and after a 15-min infusion of parathyroid hormone (PTH) in 7 normals, 13 patients with typical primary hyperparathyroidism (1HPT), and 6 patients with familial hypocalciuric hypercalcemia (FHH). Nephrogenous urinary cAMP excretion rate reached a peak during the first or second 30 min urine collection interval after the start of the PTH infusion in all subjects. cAMP concentration in plasma reached a peak within 5--20 min of the start of the infusion and then decreased with an initial half-time of 15 min. The peak value of nephrogenous urinary cAMP excretion rate was lower in the group with 1HPT than in the group with FHH or in normals (119 vs, 275 vs. 204 nmol/100 ml glomerular filtrate; P less than 0.0 5 for both comparisons). Similarly, the peak value of plasma cAMP concentration was less in 1HPT subjects than in FHH patients or in normals (11.1 vs. 17.1 vs. 16.6 nmol/100 ml, respectively; P less than 0.05 for both comparisons). For purposes of diagnostic classification, the two hypercalcemia groups could be more completely separated by the values of either the renal calcium to creatinine clearance ratio or the plasma PTH concentration than by the values of inidices of cAMP response to PTH. The differences in cAMP response to PTH between FHH and 1HPT patients could be secondary to differences in circulating PTH concentrations (these are lower in subjects with FHH) or could reflect a renal lesion more closely related to the underlying etiology of FHH.
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PMID:Adenosine 3',5'-monophosphate response to parathyroid hormone: familial hypocalciuric hypercalcemia versus typical primary hyperparathyroidism. 624 24

A study of 28 consecutively admitted patients with active acromegaly revealed the following results with regards to calcium and phosphate metabolism. When compared with controls, there was an increase in serum calcium levels corrected for total protein, urinary calcium was increased, but the tubular re-absorption of calcium was normal. There was a negative correlation between the urinary cAMP and calcium excretion indicating that hyperabsorption of calcium from the gut is the cause of the increased urinary calcium excretion. Serum phosphate values were increased in acromegalics and correlated well with TmP/GFR which was also increased. Immunoreactive parathyroid hormone (PTH) was increased in 5 patients, three of whom had hypercalcaemia. In the remaining patients the PTH values were scattered within the normal range. The urinary cAMP/creatinine ratio was increased in acromegalics, but most of this difference was abolished when urinary cAMP was expressed relative to 100 ml of glomerulus filtrate. It is concluded that parathyroid hyperactivity is a feature of acromegaly.
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PMID:Calcium and phosphate metabolism in acromegaly. 625 98

Impairment of urine-concentrating ability is common in persons with chronic hypercalcemia. We assessed urine-concentrating ability in 40 patients with typical primary hyperparathyroidism and 10 patients with familial hypocalciuric hypercalcemia, a disorder resembling typical primary hyperparathyroidism but lacking some of its clinical complications. Urine-concentrating ability was determined during a dehydration test of 18-22 h. The two patient groups were comparable with respect to serum calcium concentration and creatinine clearance. In the group with familial hypocalciuric hypercalcemia, the duration of hypercalcemia was probably greater, because it commences during infancy; the urinary excretion rate for calcium was lower [6.6 +/- 5.4 (mean +/- 1 SD) vs. 14.8 +/- 7.5 meq/day; P less than 0.005]. Patients with familial hypocalciuric hypercalcemia showed higher maximal urinary osmolality (800 +/- 150 vs. 664 +/- 130 mosmol/kg; P less than 0.0005). Among the patients with typical primary hyperparathyroidism, there was a negative association between maximal urinary osmolality and urinary cAMP (r = -0.40; P less than 0.05), but there was no significant relation between maximal urinary osmolality and the urinary excretion rate for calcium. Among 18 patients retested within 1 month after surgical correction of typical primary hyperparathyroidism, urine-concentrating ability did not improve. In patients with typical primary hyperparathyroidism, impairment in urine-concentrating ability reflects features of the chronic disease state, as it is not rapidly reversible by correction of that state. However, in patients with familial hypocalciuric hypercalcemia, longstanding hypercalcemia is not associated with obvious impairment of urine-concentrating ability. Complete or partial freedom from impairment of urine-concentrating ability and from calcareous renal disease are expressions of the generally mild course in familial hypocalciuric hypercalcemia.
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PMID:Maximal urine-concentrating ability: familial hypocalciuric hypercalcemia versus typical primary hyperparathyroidism. 625 92


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