Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0221002 (primary hyperparathyroidism)
 4,921 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1,25-Dihydroxycholecalciferol [1,25(OH)2D], besides its role in calcium and phosphorus homeostasis, is also an important immunoregulatory molecule. Plasma levels of this hormone may be normal or elevated in patients with primary hyperparathyroidism. 1,25(OH)2D has been reported to inhibit production of the cytokines interleukin-2 (IL-2) and IL-6. In the present study, we examined the effect of parathyroid adenoma excision on serum IL-2 receptor (IL-2R) levels and the release and production of IL-2R and IL-6 by peripheral blood lymphocytes (each measurement was performed twice). Ten patients (5 females and 5 males aged 45 to 78 years) with primary hyperparathyroidism were enrolled in the study. The diagnosis of primary hyperparathyroidism was based on the presence of asymptomatic hypercalcemia, hypophosphatemia, and elevated serum intact PTH levels. Three weeks after removal of the parathyroid adenoma, there was a significant increase in the serum level of IL-2R, as well as the PHA-stimulated peripheral blood lymphocyte production of IL-6 and release of IL-2R. The results indicate that the removal of a parathyroid adenoma in patients with primary hyperparathyroidism causes a significant increase in IL-2R and IL-6 levels. The mechanism by which hyperparathyroidism may affect these cytokines and how they seem related to the levels of vitamin D is discussed.
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PMID:Effect of parathyroid adenoma excision on interleukin-6 (IL-6) and IL-2 receptor levels. 1069 Sep 43

IL-6 and IL-11 are two cytokines that increase osteoclast formation and augment bone resorption. PTH stimulates the production of both cytokines by human osteoblast-like cells. Circulating levels of IL-6 are elevated in patients with states of PTH excess and correlate strongly to markers of bone resorption. In contrast, serum levels of IL-11 were significantly reduced in patients with primary hyperparathyroidism compared with values in euparathyroid controls. Further, after successful parathyroid adenomectomy, circulating levels of IL-6 fell, whereas IL-11 levels increased. Five-day infusions of human PTH-(1--84) in rodents resulted in a significant decline in mean circulating levels of IL-11, whereas IL-6 levels significantly increased. Pretreatment of cells and mice with neutralizing serum to IL-6 enhanced PTH-induced IL-11 production compared with the effect of pretreatment with nonimmune sera. These data indicate that IL-6 negatively regulates IL-11 production in vivo and in vitro. Analysis of steady state mRNA levels in SaOS-2 cells indicated that this effect is posttranscriptional. As both IL-6 and IL-11 stimulate osteoclast formation, down-regulation of IL-11 by IL-6 may help modulate the resorptive response to PTH.
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PMID:IL-6 negatively regulates IL-11 production in vitro and in vivo. 1151 62

It remains unclear whether mild primary hyperparathyroidism results in accelerated bone loss, with recent studies reaching different conclusions. This could be due to intrinsic differences in disease activity not captured by the classical biochemical markers of the disease. Because circulating levels of IL-6 and IL-6 soluble receptor (IL-6sR) are reportedly elevated in patients with hyperparathyroidism, we sought to determine whether measures of this cytokine axis could be helpful in determining the risk for bone loss in hyperparathyroidism. We prospectively followed 23 patients with hyperparathyroidism for 22 +/- 1.5 months and found that baseline circulating levels of IL-6sR correlated significantly with rates of bone loss at the total femur (r = -0.53, P < 0.01). Furthermore, the combination of a serum IL-6sR in the upper tertile (> or=45.6 ng/ml) and IL-6 in the upper half (> or =11.8 pg/ml) of values in the whole group defined a subset of patients with a significantly greater rate of yearly bone loss at the total femur than the remainder of the group (-2.6 +/- 1.3% vs. +0.4 +/- 0.3%, P < 0.05). We conclude that the combined measurements of serum IL-6sR and IL-6 may be helpful in identifying patients with untreated hyperparathyroidism who are more likely to experience bone loss at the total femur.
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PMID:Circulating levels of interleukin-6 soluble receptor predict rates of bone loss in patients with primary hyperparathyroidism. 1241 55

Parathyroid hormone (PTH) and PTH-related protein/peptide (PTHrP) bind to the same PTH/PTHrP receptor and stimulate osteoblasts to secrete pro-inflammatory cytokines like interleukin (IL)-6. In patients with primary hyperparathyroidism, elevation of plasma levels of tumor necrosis factor (TNF)-alpha and IL-6 was also described. We, therefore, postulated that PTHrP secreted from cancer cells stimulates the secretion of cytokines and causes increases in their blood levels. Blood concentrations of several cytokines (TNF-alpha, IL-1beta, IL-5, IL-6, IL-8, IL-11 and IL-12) in cancer-bearing patients with or without elevation of blood PTHrP were measured by ELISA. The patients with high plasma PTHrP levels (n=29, intact PTHrP: 8.5 +/- 1.4 pmol/l, normal: <1.1) had higher serum type 1 collagen C-telopeptide (ICTP). Twenty of the patients were hypercalcemic. Plasma concentrations of TNF-alpha, IL-6 and IL-8 were significantly increased in patients with high PTHrP, in either the presence or absence of hypercalcemia. The concentrations of TNF-alpha and IL-6 were also significantly correlated with those of PTHrP. Our observations indicate that high plasma levels of PTHrP in cancer-bearing patients contribute not only to the development of hypercalcemia, but also to the development of the syndrome caused by an excess of pro-inflammatory cytokines.
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PMID:Elevation of circulating plasma cytokines in cancer patients with high plasma parathyroid hormone-related protein levels. 1450 17

Parathyroid hormone (PTH) promotes IL-6 secretion by osteoblasts, and may also up-regulate IL-6 production in the liver and adipose tissue; this may explain why serum IL-6 is markedly elevated in primary hyperparathyroidism, and low in hypoparathyroidism. IL-6 is the chief stimulus to hepatic production of many acute phase reactants, notably fibrinogen and C-reactive protein (CRP). Mild secondary hyperparathyroidism is common in elderly people, particularly at high latitudes during the winter, owing to poor vitamin D status. This may rationalize evidence that acute phase proteins show seasonal variations and are typically elevated in the elderly, whereas leisure physical activity is associated with a reduction in these proteins. In a recent clinical trial targeting elderly chronically ill patients, administration of vitamin D reduced serum levels of both CRP and IL-6; further such studies should assess the impact of physiologically meaningful doses of vitamin D on acute phase reactants in elderly subjects likely to have poor vitamin D status. Since elevations of CRP and fibrinogen may increase risk for thromboembolic vascular events, these considerations may help to explain the excess of coronary mortality observed during winter months, and suggest a role for supplemental vitamin D in preservation of vascular health. Moderate alcohol intake is associated with reduced serum PTH as well as decreased levels of CRP and fibrinogen; conceivably, modulation of PTH mediates, at least in part, the favorable impact of moderate drinking on the acute phase reactants.
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PMID:Secondary hyperparathyroidism promotes the acute phase response -- a rationale for supplemental vitamin D in prevention of vascular events in the elderly. 1578 May 4