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)

We have studied the effect of intravenous calcitriol [1,25(OH)2D] therapy (1 microgram at the end of each dialysis session) on parathyroid secretory curves of hemodialyzed patients with near-normal basal intact (< 10 pmol/l, n = 7; NNBI) or elevated basal intact (> 10 pmol/l, n = 6; EBI) parathyroid hormone (PTH; iPTH) levels. These results were compared with those obtained in matched normal individuals (N). Our main objective was to define the influence of intravenous 1,25(OH)2D therapy on the set point of iPTH stimulation in relation to the severity of secondary hyperparathyroidism. A complete parathyroid function was obtained by CaCl2 and Na2EDTA infusions in 14 N and by modification of the dialysate calcium content in 13 hemodialyzed patients. Ionized calcium (Ca2+) and iPTH were measured regularly during hypo- and hypercalcemia. Parathyroid secretory curves were derived from these data. Both groups of patients had lower basal Ca2+ (NNBI 1.16 +/- 0.05; EBI 1.10 +/- 0.03; N 1.25 +/- 0.04 mmol/l; p < 0.001) and higher basal iPTH (NNBI 6.3 +/- 2.5; EBI 49.2 +/- 39.5; N 2.5 +/- 0.8 pmol/l; p < 0.01) levels than N with more extreme values in EBI than in NNBI patients (p < 0.001). NNBI patients had stimulated iPTH levels similar to N (18.4 +/- 7.1 vs. 17.3 +/- 7.2 pmol/l), while these levels were markedly increased in EBI patients (80.7 +/- 46.0 pmol/l; p < 0.001). After 1,25(OH)2D therapy, Ca2+ increased to 1.16 +/- 0.03 mmol/l in EBI and normalized in NNBI patients (1.25 +/- 0.07 mmol/l). Stimulated iPTH decreased by 30% in NNBI (p < 0.05) and by 21% in EBI patients (NS). These two factors contributed to a decrease in basal iPTH by 52% in NNBI (p < 0.05) and by 40% in EBI (p < 0.01). The set point of iPTH stimulation was lower than in N (1.18 +/- 0.04 mmol/l) and increased with intravenous 1,25(OH)2D therapy from 1.09 +/- 0.03 to 1.16 +/- 0.05 mmol/l in NNBI (p < 0.05) and from 1.08 +/- 0.04 to 1.12 +/- 0.04 mmol/l in EBI patients (p < 0.05). The set points and changes in set point were correlated with basal Ca2+ (r = 0.56; p = 0.003) and changes in basal Ca2+ (r = 0.64; p = 0.04) observed before and during therapy. The starting position of each patient on his secretory curve before and after 1,25(OH)2D therapy was inversely related to his starting Ca2+ concentration (n = 26; r = -0.66; p = 0.0003). Taking this into account improved the relationship between Ca2+ concentration and the set point of iPTH stimulation by Ca2+ in a stepwise regression (R2 = 0.62; p = 0.0003). However, no correlation was found between set points and stimulated iPTH values. We concluded that 1,25(OH)2D therapy induced an increase in the set point of PTH stimulation in hypocalcemic hemodialyzed patients related to a similar increase in basal Ca2+ concentration. This is in part related to the starting position of each patient on his secretory curve which will affect his set point in relation to the hysteresis phenomenon in iPTH secretion. But the set point of PTH stimulation is also related to the basal ionized calcium concentration by mechanisms yet to be elucidated.
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PMID:Intravenous 1,25(OH)2D therapy increases the intact parathyroid hormone secretion set point in hemodialyzed patients. 905 66

The success of parathyroid surgery is determined by the identification and removal of all hyperactive parathyroid tissue. Ectopic location of parathyroid tumours and fibrosis due to previous operations can cause failure of parathyroidectomy. Parathyroid tumours accumulate and retain 2-methoxyisobutylisonitrile (MIBI) labelled with technetium-99m. This study assesses the value of intra-operative localization of parathyroid tumours using a hand-held gamma detector in patients with hyperparathyroidism and parathyroid cancer. Twenty patients undergoing their first operations for hyperparathyroidism, 15 patients undergoing reoperations for either persistent or recurrent hyperparathyroidism and two patients with parathyroid cancer were studied. Radioactivity in the neck and the mediastinum was recorded by a gamma detector after administration of 370 MBq 99m Tc-MIBI. Surgical findings and postoperative serum levels of calcium were documented. The sensitivity of the gamma detector in identifying parathyroid tumours was 90.5% in first parathyroidectomies, 88.9% in reoperations for either persistent or recurrent hyperparathyroidism and 100% in parathyroid cancer. One false-positive result was due to a thyroid nodule. Hypercalcaemia ceased in all but one patient postoperatively. It is concluded that employment of the gamma detector is to be advocated in first parathyroidectomies when a parathyroid tumour cannot be discovered, in reoperations for either persistent or recurrent hyperparathyroidism and in surgery for parathyroid cancer.
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PMID:Intraoperative nuclear guidance in benign hyperparathyroidism and parathyroid cancer. 914 60

Although high-dose intravenous calcitriol has been shown to be effective in suppressing parathyroid hormone (PTH) secretion in dialysis patients with secondary hyperparathyroidism, an increasing number of patients is refractory to treatment. Only a few studies have evaluated the factors that can predict a favorable response to calcitriol, but contrasting results have been reported. This study was performed to evaluate the effect of high-dose intravenous calcitriol on parathyroid function and to investigate the factors that can predict a favorable response to treatment. Thirty-five dialysis patients were selected for intravenous calcitriol treatment (2 microg after dialysis for 12 months) because of increased PTH levels (>325 pg/mL). Before starting the treatment, the set point of calcium and the PTH-ionized calcium (ICa) curve was evaluated in each patient by inducing hypocalcemia and, 1 week later, hypercalcemia to maximally stimulate or inhibit PTH secretion. Parathyroid glands were assessed by high-resolution color Doppler ultrasonography. Throughout the study, calcium carbonate or acetate dosage was modified to maintain serum phosphate less than 5.5 mg/dL. Hypercalcemia was managed by reducing dialysate calcium to 5 mg/dL and, if necessary, calcitriol dose. The therapeutic goal was to reduce PTH levels below 260 pg/mL while maintaining normocalcemia. The patients who achieved the therapeutic goal were considered responders. Taking the data from the 35 patients together, we observed a significant decrease (P < 0.01) in alkaline phosphatase (from 252 +/- 106 IU/L to 194 +/- 81 IU/L) and PTH (from 578 +/- 231 pg/mL to 408 +/- 291 pg/mL), and a significant increase in serum ICa (from 5.1 +/- 0.2 mg/dL to 5.3 +/- 0.2 mg/dL; P < 0.001) after calcitriol therapy. PTH changes after therapy were not correlated to serum ICa changes, serum phosphate levels during treatment, and calcitriol dose. The response to therapy was heterogeneous because PTH levels markedly decreased over the treatment period in 18 responsive patients, whereas they increased or remained unchanged in 14 of 17 nonresponders. In three additional refractory patients, there was a decline in PTH of 20% to 35%, but this decline was associated with hypercalcemia. Pretreatment parathyroid gland size, serum ICa, PTH, maximal PTH induced by hypocalcemia, minimal PTH induced by hypercalcemia, the set point of ICa, and the ICa levels at which maximal PTH secretion and inhibition occurred were higher in the 17 refractory patients than in the 18 responsive patients. However, logistic regression analysis showed that among these parathyroid function parameters, the only significant predictors of a favorable response to calcitriol therapy were the parathyroid gland size and the set point of ICa. Throughout the study, serum phosphate and calcitriol dose were comparable in the two groups. In conclusion, the response to intravenous calcitriol therapy in dialysis patients with secondary hyperparathyroidism is heterogeneous, consisting of patients who are either responsive or refractory to treatment; refractoriness can be predicted by parathyroid volume and calcium set point.
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PMID:Long-term effects of intravenous calcitriol therapy on the control of secondary hyperparathyroidism. 915 8

Parathyroid function was studied in 14 normal dogs 1 month before and after daily i.v. administration of 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) (eight dogs), or about 50% parathyroidectomy (six dogs), to test the hypothesis that degradation of newly synthesized intact parathyroid hormone (I-PTH) is involved in parathyroid gland adjustment to a modified demand for I-PTH. Parathyroid function was studied through i.v. infusions of Na2EDTA and CaCl2 and measurement of ionized calcium (Ca2+), I-PTH and carboxyl-terminal PTH (C-PTH) at various time points. The C-PTH/I-PTH ratio was used as an index for change in the relative proportion of circulating C-PTH vs I-PTH, 1 month prior to and following each intervention. This ratio was further validated by looking at the HPLC profile of I- and C-PTH in hypo- and hypercalcemia under experimental conditions. Basal Ca2+ was unaltered 1 month after surgery, and was maintained constant in the 1,25-(OH)2D3-treated group by gradually decreasing 1,25-(OH)2D3 doses over time from 0.25 to 0.13 microgram twice daily during the last week of the experimental protocol. In this same group, basal 1,25-(OH)2D3 was increased by 65% (P < 0.0001) and basal I-PTH was decreased by 40% (P < 0.05), while basal C-PTH and the C-PTH/I-PTH ratio remained unchanged. Stimulated and non-suppressible I- and C-PTH followed the same pattern with, this time, an increase of stimulated and non-suppressible C-PTH/I-PTH ratio of 60% (P < 0.05) and 85% (P < 0.05) respectively. There was no change in basal I-PTH, C-PTH, or C-PTH/I-PTH ratio after surgery. However, stimulated I- and C-PTH were decreased by 45% (P < 0.005) and 65% (P < 0.005) respectively, with a 30% (P < 0.005) decrease of stimulated C-PTH/I-PTH ratio. There was no change in non-suppressible I-PTH, while non-suppressible C-PTH decreased by 55% (P < 0.005), with a 55% (P < 0.05) decrease in non-suppressible C-PTH/I-PTH ratio. The HPLC profiles of I- and C-PTH obtained in hypo- and hypercalcemia disclosed a similar distribution of the immuno-reactivity into peaks before and after i.v. administration of 1,25-(OH)2D3 as well as partial parathyroidectomy. This indicated that C-PTH/I-PTH ratio changes were related to different circulating levels of I- and C-PTH rather than to a different composition of I- and C-PTH. These data indicate a shift in the circulating PTH profile toward more PTH carboxyl-terminal fragments after 1 month of i.v. 1,25-(OH)2D3, but toward more intact PTH 1 month after about 50% parathyroidectomy, possibly reflecting adjustments in PTH degradation induced by a modified demand for I-PTH. Although these changes are most likely modulated at the parathyroid gland level, we cannot formally eliminate participation of the hormone's peripheral metabolism.
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PMID:Adaptation of parathyroid function to intravenous 1,25-dihydroxyvitamin D3 or partial parathyroidectomy in normal dogs. 939 15

The purpose of this study was to assess the diagnostic utility of parathyroid ultrasonography to differentiate causes of hypercalcemia in dogs. We analyzed qualitative and quantitative ultrasound imaging findings and clinical pathology data from 33 dogs that underwent parathyroid ultrasound examination as part of the diagnostic evaluation for hypercalcemia. Diagnoses of the diseases causing hypercalcemia included parathyroid carcinoma (n = 5), parathyroid adenoma (n = 15), parathyroid adenomatous hyperplasia (n = 6), chronic renal insufficiency (n = 3), and hypercalcemia of malignancy (n = 4). All parathyroid lesions were round or oval and hypoechoic compared with surrounding thyroid parenchyma. Adenomatous and adenocarcinomatous glands were 4 mm or larger in longest linear measurement on US examination and were statistically significantly larger than hyperplastic glands. (p < 0.001) Linear measurements of parathyroid glands acquired at the time of ultrasound examination correlated well with direct size determination after surgical excision. (r2 = 0.9, p < 0.0001) Parathyroid lesions > or = 4 mm are highly suspicious for parathyroid adenoma or carcinoma, while US lesions < 4 mm most likely represent primary adenomatous hyperplasia or secondary parathyroid hyperplasia. Parathyroid size estimation from ultrasound examination is an accurate predictor of true size.
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PMID:High-resolution parathyroid sonography. 940 14

Parathyroid-hormone-related protein (PTHrP) is the main mediator of the humoral hypercalcemia of malignancy. It is also detected in many normal adult and fetal tissues. Altered calcium metabolism occurs in sarcoidosis, and two cases of sarcoidosis with hypercalcemia and elevated plasma PTHrP are described. An archival study of 20 lymph node biopsies with the pathological diagnosis of sarcoidosis was performed. Immunohistochemistry using a polyclonal antiserum to human PTHrP and in situ hybridization using a riboprobe to human PTHrP were performed on the lymph node biopsies. Immunohistochemistry for PTHrP was also performed on the biopsies from the two cases with elevated plasma levels. Immunohistochemical analysis detected PTHrP in macrophages within granulomata in 17 of the 20 (85%) biopsies. In situ hybridization detected a positive signal for messenger RNA in the granulomata of 11 of 19 (58%) biopsies. PTHrP immunoreactivity and PTHrP gene expression are present in sarcoid granulomata. PTHrP may contribute to the hypercalcemia of sarcoidosis.
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PMID:Parathyroid-hormone-related protein in sarcoidosis. 942 18

Primary hyperparathyroidism, characterized by hypersecretion of parathyroid hormone (PTH) leading to hypercalcemia and relative hypophosphatemia, is quite common in the elderly. Most patients with primary hyperparathyroidism have only mild hypercalcemia and are symptomless. But others experience various other organ diseases. Primary hyperparathyroidism is also associated with cardiovascular abnormalities, including QT interval shortening, heart block, cardiac arrhythmias, hypertension, myocardial hypertrophy, myocardial calcification and, though rarely, with valvular heart disease. We described a case of primary hyperparathyroidism associated with cardiac abnormalities. An 82-year-old male presented with the complaints of chest discomfort, fatigue, general weakness, nausea and vomiting over a period of months and was admitted in July 1996. Physical examination with heart auscultation showed a pansystolic murmur over the right sternal border and apex region, and a blowing diastolic murmur over the left sternal border. Biochemistry profiles revealed elevations of serum calcium (14.3 mg/dl) and chloride/phosphate ratio (> 33). Endocrinological studies showed elevations of serum PTH-C (4.8 ng/ml) and PTH-intact (705 pg/ml) concentrations. Kidney ultrasonography revealed a left renal stone. A spine X-ray revealed spondylosis and a compression fracture of the lumbar-spine with osteoporotic change. Thyroid ultrasonography and Thallium (Tl201)-technetium (Tc99m) subtraction scan showed parathyroid adenoma in the low pole of the right thyroid bed. Parathyroid aspiration cytology revealed few and discrete cells. Echocardiogram revealed moderate to severe aortic valvular calcification as well as stenosis with moderate aortic regurgitation, mitral regurgitation and myocardial calcification. The patient received parathyroidectomy one month later. During his postoperative days, he suffered from muscle twitching with positive Trousseau's sign and Chvostek's sign. The patient received calcium carbonate and vitamin D for hypocalcemia, diltiazem and capoten for his heart problems. A repeated echocardiogram two months after surgery showed no improvement of valvular calcification.
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PMID:Primary hyperparathyroidism with cardiac abnormalities: a case report. 950 84

Hypercalcemia is an important complication in multiple myeloma as well as T-cell leukemia/lymphoma, and is moderately common in high and intermediate grade non-Hodgkin's lymphoma. The underlying mechanism has been unclear because the neoplastic cells are usually present in the bone marrow, where they are in a position to produce short range effects on bone resorption which are difficult to identify. This contrasts with the situation in hypercalcemia associated with non-metastatic carcinoma, where it has been clearly demonstrated that the most common cause is release from the tumor of a humoral mediator, Parathyroid Hormone-related Protein (PTHrP). Roles have been advocated in multiple myeloma for release of a number of other cytokines with osteolytic capacity on the basis of their enhancement of osteolytic activity in cultured fetal rat bone, although a causal relationship in patients has not been established. PTHrP has more recently been implicated in the genesis of hypercalcemia in patients with hematological malignancies by the demonstration in a proportion of cases of increased circulating levels of PTHrP, comparable to those in hypercalcemia due to cancer. Immunohistochemical studies indicate neoplastic hemopoietic cells can contain PTHrP, and thus have the capacity to act in a paracrine manner to enhance local bone resorption and contribute to the development of hypercalcemia.
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PMID:Parathyroid hormone-related protein in hypercalcemia associated with hematological malignancy. 964 63

Auditory Brainstem Evoked Potentials (ABEPs) and pure tone audiograms were obtained from 24 patients with parathyroid dysfunction (17 hypercalcemia and 7 hypocalcemia) and 12 patients with thyroid dysfunction (6 hyperthyroid and 6 hypothyroid) and from 10 control subjects. ABEPs were characterized by I-V interpeak latency difference at 10/sec click rate and by the effect of increasing stimulus rate to 55/sec. None of the ABEP measures were significantly affected by levels of serum calcium, thyroid hormones or their interactions. Moreover no correlation was found between biochemical and electrophysiological measures. This stability of ABEP measures contrasts with earlier reports on acute effects of calcium and thyroid hormonal levels on auditory brainstem evoked potentials. We propose that chronic calcium or thyroid hormonal homeostatic changes are associated with adaptive mechanisms resulting in normal function of the auditory brainstem.
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PMID:Auditory brain-stem evoked potentials in patients with thyroid and parathyroid dysfunction: adaptation to chronic hormonal dysequilibrium. 1052 8

The effects of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] and its analogue 22-oxa-1,25(OH)2D3 (22-oxacalcitriol) (OCT) on calcium and bone metabolism were examined in an animal model of hypercalcemia with continuous infusion of parathyroid hormone-related peptide (PTHrP), to determine whether active vitamin D could counteract the skeletal action of PTHrP in addition to its reported effect in suppressing the production of PTHrP in cancer cells. Parathyroid glands were removed from 8-week-old Sprague-Dawley rats to eliminate the confounding effects of endogenous PTH. Animals were then continuously infused with human PTHrP(1-34) at a constant rate via osmotic minipumps for 2 weeks, and at the same time treated orally or intravenously with OCT or 1,25(OH)2D3 four to nine times during the 2-week period. Under these conditions, OCT and, surprisingly, 1,25(OH)2D3 alleviated hypercalcemia in a dose-dependent manner. 1,25(OH)2D3 and OCT suppressed the urinary excretion of deoxypyridinoline, although they did not affect renal calcium handling, suggesting that the antihypercalcemic effect is attributable to the inhibition of bone resorption. These active vitamin D compounds also counteracted the effects of PTHrP at the proximal renal tubules, as reflected by a decrease in phosphate excretion. Histomorphometric analysis of bone revealed a dose-related decrease in parameters of bone resorption. These results suggest that 1,25(OH)2D3 as well as OCT has the potential to alleviate hypercalcemia, at least in part, through the inhibition of bone resorption in hypercalcemic rats with constant PTHrP levels. We propose that the main function of active vitamin D in high bone-turnover states is to inhibit bone resorption, and this may have important implications for the understanding of the role of active vitamin D in the treatment of metabolic bone diseases, such as osteoporosis.
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PMID:1,25-dihydroxyvitamin D3 as well as its analogue OCT lower blood calcium through inhibition of bone resorption in hypercalcemic rats with continuous parathyroid hormone-related peptide infusion. 1064 27


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