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

The "syndrome of inappropriate calcitriol secretion" may be observed in diseases with disseminated granulomas. The main examples are sarcoidosis and tuberculosis, but it can also be observed in fungal infections, in granulomas due to foreign bodies and in lymphomas. The syndrome is due to autonomous production of 1 alpha hydroxylase by granulomas. The insuing synthesis of calcitriol escapes normal regulation by serum calcium and phosphate levels. The syndrome includes hypercalcemia, hypercalciuria, high 1,25(OH)2D3 serum levels and reduced PTH secretion. It can supervene in anephric or hypoparathyroid patients. The notion that calcitriol may be secreted extrarenally is new. It could have important bearings on several issues in nephrology, immunology and oncology.
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PMID:[Inappropriate calcitriol secretion syndrome]. 295 94

Hypercalcemia and hypercalciuria in sarcoidosis are thought to result from the endogenous overproduction of an active vitamin D metabolite. We employed primary cultures of pulmonary alveolar macrophages from two patients with biopsy-proven pulmonary sarcoidosis and a recent or current clinical abnormality in calcium metabolism to synthesize in vitro a 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3]-like metabolite from 25-hydroxyvitamin D3 (25OHD3). The macrophage metabolite cochromatographed with [3H]1,25-(OH)2D3 on normal phase and reverse phase high performance liquid chromatography and was bound with high affinity by the chick intestinal receptor for 1,25-(OH)2D3. On UV spectroscopy, the metabolite possessed the carbon-5,7,10 (19) cis-triene chromophore characteristic of a vitamin D sterol. Electron impact mass spectrometry of trimethylsilyl ether derivatives of the metabolite revealed a mass fragmentation pattern similar to that of the trimethylsilyl ether derivative of authentic 1,25-(OH)2D3. The incubation of cultured macrophages from two patients with idiopathic pulmonary fibrosis and two with scleroderma with [3H]25OHD3 did not result in production of a metabolite with the chromatographic identity of 1,25-(OH)2D3. These data indicate that the metabolite of 25OHD3 synthesized by sarcoid macrophages in vitro is 1,25-(OH)2D3 and that the macrophage is a synthetic source of the sterol metabolite in sarcoidosis.
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PMID:Isolation and structural identification of 1,25-dihydroxyvitamin D3 produced by cultured alveolar macrophages in sarcoidosis. 298 38

Serum angiotensin-converting enzyme (SACE) was measured in 14 patients (eight women and six men) with sarcoidosis and hypercalcemia. Thirteen patients were treated with prednisone, and 12 achieved normal or nearly normal serum calcium values. Two patients had coexistent hyperparathyroidism. Seven of eight patients with serial SACE measurements exhibited parallel falls in SACE and serum calcium levels. Eleven patients were successfully treated with alternate-day prednisone regimens. The data suggest that serial SACE measurements are useful in the evaluation and management of sarcoidosis with hypercalcemia. In patients with sarcoidosis, the reduction of SACE levels during glucocorticoid treatment may be due to a suppression of granuloma formation. Concomitant falls in serum calcium level suggest an important role of the granuloma or its cellular precursors in vitamin D metabolism.
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PMID:Serum angiotensin-converting enzyme activity. Its use in the evaluation and management of hypercalcemia associated with sarcoidosis. 298 11

We describe two patients with diffuse non-Hodgkin's lymphoma, hypercalcemia, and increased activity of serum angiotensin-converting enzyme. A mechanism similar to that operative in sarcoidosis is speculated to have caused the hypercalcemia. A lymphokine elaborated by the malignant lymphoma may cause activated macrophages to produce 1,25-dihydroxyvitamin D3.
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PMID:Non-Hodgkin's lymphoma associated with hypercalcemia and increased activity of serum angiotensin-converting enzyme. 301 90

Hypercalcemia is a common biochemical abnormality. It is usually possible to make a presumptive diagnosis of its cause by relatively simple means. In a large majority of cases this involves differentiating between primary hyperparathyroidism and malignancy-associated hypercalcemia. Clinical evaluation and parathyroid hormone assay are particularly useful. Since the management of hypercalcemia in the short term generally involves non-specific measures such as rehydration, the inability to make an immediate accurate diagnosis presents less of a problem than might otherwise be the case. The definitive diagnosis of hyperparathyroidism, malignancy and sarcoidosis requires histological confirmation.
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PMID:Clinching the diagnosis: an approach to the investigation of hypercalcemia. 302 Apr 90

A review is given on S-angiotensin-converting enzyme (SACE) and its clinical value, based upon 327 sarcoidosis patients and 1,274 patients with various disorders. SACE was elevated in 55% of the sarcoidosis patients, although with a higher frequency in those with active disease. Erythema nodosum was associated with normal initial SACE, subsequently rising, and sarcoid hypercalcaemia was consistently followed by elevated SACE. In non-sarcoid patients, elevated SACE was observed in only 10 cases. The sensitivity and specificity were 0.55 and 0.99, respectively, and the positive and negative predictive values were 0.95 and 0.90, respectively. Elevated SACE pointed strongly towards the presence of sarcoidosis, although reservations must be made in patients with liver disorders, diabetes mellitus, hyperthyroidism, asbestosis or silicosis which are rather common disorders also associated with elevated SACE. Normal SACE does not exclude sarcoidosis.
Sarcoidosis 1985 Mar
PMID:Angiotensin-converting enzyme activity in sarcoidosis and other disorders. 303 89

In an attempt to identify factors that may indicate which patients with sarcoidosis are likely to manifest a clinical abnormality in calcium homeostasis, we measured serum concentrations of calcium, angiotensin converting enzyme activity (ACE), 25-hydroxyvitamin D (25-OH-D), 1,25-dihydroxyvitamin D (1,25-(OH)2-D), and immunoreactive parathyroid hormone (iPTH) in 19 patients with biopsy proven sarcoidosis, seven of whom were either frankly hypercalcemic or hypercalciuric. These data were compared to the ability of cultured pulmonary alveolar macrophages (PAM) from the same patients to metabolize [3H]25-OH-D3 to [3H]1,25-(OH)2-D in vitro. All seven hypercalcemic/hypercalciuric patients with sarcoidosis had a serum ACE level greater than 40 IU/L (normal less than 35 IU/L). All five patients with hypercalcemia (Ca greater than or equal to 10.5 mg/dl) had a serum 1,25-(OH)2-D concentration above the normal range (greater than 60 pg/ml), and in all 19 patients the serum calcium was positively correlated to the serum 1,25-(OH)2-D concentration (r = 0.55, p less than 0.01). The capacity of PAM to synthesize [3H]1,25-(OH)2-D3 in vitro was. with one exception, greater in cells from patients with diffuse infiltrative pulmonary disease (roentgenographic stage II or III) and positively correlated to the serum calcium concentration (r = 0.72, p less than 0.001) and serum ACE (r = 0.43, p less than 0.05). Cultured PAM from the five hypercalcemic patients, all of whom demonstrated diffuse pulmonary disease on chest x-ray, showed a [3H]1,25-(OH)2-D3 synthetic capacity in vitro 2.5-fold greater than that for group as a whole and 6-fold greater than in cells from nonhypercalcemic patients with sarcoidosis.
Sarcoidosis 1986 Mar
PMID:Biochemical indicators of disordered vitamin D and calcium homeostasis in sarcoidosis. 303 83

1,25-Dihydroxyvitamin D (1,25-(OH)2D) plays a crucial role in the maintenance of blood calcium and phosphorus levels and in normal skeletal mineralization. The concentration of this metabolite in the blood is, by necessity, tightly regulated. The most important stimuli for renal 1,25-(OH)2D synthesis include parathyroid hormone (PTH), its second messenger cyclic adenosine monophosphate (cAMP) and phosphate deprivation. Hypocalcemia and calcitonin, initially thought to act via stimulation of PTH release, have now been shown to directly stimulate 1-hydroxylation. Estrogens also increase 1,25-(OH)2D production, probably by upregulating renal PTH receptors. Inhibitors of the renal 25-(OH)D 1 alpha-hydroxylase include 1,25-(OH)2D itself, hypercalcemia, and phosphate loading. The PTH-vitamin D axis as modulated by the serum ionized calcium level controls adaptation to alterations in dietary calcium and sodium intake and to changes in skeletal turnover based on the level of physical activity. Although normally the renal production of 1,25-(OH)2D is tightly regulated and changes little in response to vitamin D challenge, there are certain conditions in which 1,25-(OH)2D appears to be substrate-dependent. These include hypoparathyroidism, hyperparathyroidism, vitamin D deficiency, sarcoidosis and the anephric state, conditions in which PTH is not well-modulated by alterations in serum ionized calcium or in which extrarenal synthesis of 1,25-(OH)2D occurs. In several disorders, including absorptive hypercalciuria, pseudohypoparathyroidism, hypophosphatemic rickets, and tumoral calcinosis, the regulation of the renal 1 alpha-hydroxylase appears to be altered.
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PMID:Normal and abnormal regulation of 1,25-(OH)2D synthesis. 306 16

A patient with sarcoidosis with elevated 1,25-dihydroxy vitamin D levels, hypercalcemia, nephrolithiasis, and moderate azotemia is presented because of development of metastatic pulmonary calcification which was diagnosed by radioisotope scanning and tissue biopsy.
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PMID:Metastatic pulmonary calcification in sarcoidosis. 324 21

We determined the metabolic clearance and production rates of 1,25-dihydroxyvitamin D [1,25-(OH)2D] in 5 patients with sarcoidosis who had either hypercalciuria or hypercalcemia to examine whether abnormalities in the metabolism of this hormone existed. The mean MCR in the 5 patients with sarcoidosis [40 +/- 9 (+/- SD) mL/min] was similar to that in 13 normal subjects (37 +/- 6 mL/min) and that in 9 patients with absorptive hypercalciuria and renal stones (35 +/- 4 mL/min). However, the mean serum 1,25-(OH)2D concentration was significantly higher in the patients with sarcoidosis (211 +/- 60 pmol/L) than in either of the other 2 groups. The mean 1,25-(OH)2D production rate was markedly elevated in the patients with sarcoidosis (12.4 +/- 5.3 mumol/day), being more than 2-fold greater than the normal mean value (5.4 +/- 1.2 mumol/day). The highest production rates were found in patients with hypercalcemia, whereas subjects with hypercalciuria had production rates comparable to those in the patients with absorptive hypercalciuria. These data indicate that there is no impairment in the clearance of 1,25-(OH)2D in patients with sarcoidosis and that the elevated serum 1,25-(OH)2D levels are due to an increase in its production rate.
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PMID:Enhanced production rate of 1,25-dihydroxyvitamin D in sarcoidosis. 333 11


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