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)

To test the hypothesis that lithium is a general inhibitor of hormone-activated adenylate cyclase, we infuse parathyroid hormone (PTH) into human subjects prior to and during lithium carbonate administration. PTH infusion caused a significant increase in urinary cyclic AMP and urinary phosphate excretion. There was no significant difference in these responses in the lithium compared to the control period. In four patients with primary hyperparathyroidism, lithium had no significant effect on serum calcium or phosphate or on tubular reabsorption of phosphate. The data do not substantiate the hypothesis that lithium (at therapeutic concentrations) is a general inhibitor of hormonally-activated adenylate cyclase, nor do they support its potential clinical utility in primary hyperparthyroidism.
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PMID:Lithium does not inhibit the parathyroid hormone-mediated rise in urinary cyclic AMP and phosphate in humans. 18 15

Increased urinary excretion of cAMP is a common finding in patients with primary hyperparathyroidism. We report a patient with hypercalcemia, primary hyperparathyroidism, vitamin D deficiency and high nephrogenous cAMP that fell to low levels during the course of a protracted illness. Surgical removal of a large parathyroid cystic adenoma was associated with a decrease in plasma calcium. Because of the relatively low nephrogenous cAMP with high plasma iPTH the biological activity of the fluid aspirated from the adenoma was examined. Acute clearance studies were performed in parathyroidectomized rats and their response to the parathyroid fluid was compared with the response of synthetic PTH. Similar phosphaturic responses to PTH and the aspirated fluid were recorded and were preceded by similar increments in nephrogenous cAMP. Thus the discrepancy between the high plasma calcium, high PTH and the low nephrogenous cAMP seen in our patient was related to impaired cAMP production by the renal adenylate cyclase. There was no evidence for a hormone with a different biological activity. The impaired formation of cAMP may reflect a combined result of several factors including downregulation of renal adenylate cyclase, phosphate depletion and vitamin D deficiency state.
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PMID:Impaired production and decreased urinary excretion of adenosine 3',5'-monophosphate in primary hyperparathyroidism with vitamin D deficiency. 284 40

We report a two-step immunochemical method for estimating serum intact PTH, as defined by immunochemical methods, and its validation by a newly developed osteosarcoma cell adenyl cyclase stimulation assay for PTH bioactivity. The first step involves extraction and concentration of serum PTH moieties with solid phase amino-terminal PTH antibodies; in the second step, the initial PTH immunoextract is analyzed with a sensitive midregion immunoassay. Intact PTH can thus be detected in virtually all normal subjects. Intact PTH levels in our group of primary hyperparathyroid persons average nearly 20 times higher than normal and do not overlap the normal range. Intact PTH is also elevated in chronic renal disease, but less dramatically than in primary hyperparathyroidism. Since total PTH immunoreactivity (intact plus fragments) is much higher in renal disease patients than in persons with primary hyperparathyroidism, serum intact PTH in renal disease apparently comprises a much smaller fraction of total circulating PTH immunoreactivity than in primary hyperparathyroidism. The finding that intact PTH accounts for a large portion of total circulating PTH immunoreactivity in primary hyperparathyroidism is contrary to published reports by us and others. Some of the possible reasons for the differences between our present results and previous reports are examined.
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PMID:Estimation of biologically active intact parathyroid hormone in normal and hyperparathyroid sera by sequential N-terminal immunoextraction and midregion radioimmunoassay. 631 57

To examine whether alterations in parathyroid adenylate cyclase might be associated with glandular hyperfunction, we compared enzyme activity in membranes from 7 normal glands with activity from 18 abnormal and 5 noninvolved glands from patients with primary hyperparathyroidism. Compared with the normal glands, the specific enzyme activity after full stimulation with guanyl-5'yl imidodiphosphate was significantly decreased in both hyperplastic and noninvolved glands from the hyperparathyroid subjects. While the enzyme activity of all tissues could be suppressed by calcium, a twofold higher calcium concentration was required for comparable suppression of the enzyme from adenomas as compared with normal or noninvolved glands. Alterations in the adenylate cyclase complex of hyperplastic parathyroid glands may explain, in part, the elevated "set point" for calcium homeostasis in primary hyperparathyroidism.
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PMID:Adenylate cyclase activity in human parathyroid tissues: reduced sensitivity to suppression by calcium in parathyroid adenomas as compared with normal glands form normocalcemic subjects or noninvolved glands from hyperparathyroid subjects. 678 28

1. Plasma membranes were prepared from parathyroid adenomas in patients with primary hyperparathyroidism and from hyperplastic glands obtained from patients with chronic renal insufficiency. The basal and isoproterenol- or sodium fluoride-stimulated adenylate cyclase activities were measured in membranes in the presence of several vitamin D3 metabolites. 2. 24,25-Dihydroxycholecalciferol (10 and 1000 pmol/l) decreased isoproterenol- and sodium fluoride-stimulated adenylate cyclase activities in membranes prepared from parathyroid glands. 1,25-Dihydroxycholecalciferol (1000 pmol/l) inhibited the isoproterenol-stimulated adenylate cyclase activity. 25-Hydroxycholecalciferol and vitamin D3 had no effect on adenylate cyclase activities. Basal adenylate cyclase activity was not affected by any of th vitamin D3 metabolites tested. 3. These results indicate that 24,25-dihydroxycholecalciferol inhibits the isoproterenol- and sodium fluoride-stimulated adenylate cyclase activities in parathyroid tissues. Such an inhibition could explain the very rapid decrease in parathyroid hormone secretion after 24,25-dihydroxycholecalciferol administration that has been previously reported.
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PMID:Human parathyroid gland adenylate cyclase activity: inhibition by 24,25-dihydroxycholecalciferol in vitro. 697 85

PTH activates hormone-sensitive lipolysis in adipose tissue by an adenylate cyclase mechanism. Effects on lipoprotein synthesis and catabolism are conceivable, but have not been studied in detail so far. Information on serum lipids in primary and secondary hyperparathyroidism is conflicting. Some authors find an increase of serum lipids upon administration of PTH and in patients with primary hyperparathyroidism, while others find a decrease of serum cholesterol and serum triglycerides which reverts to normal upon parathyroidectomy in patients with primary hyperparathyroidism. In experimental models of uremia, PTH clearly plays a permissive role for the development of uremic hyperlipemia. In PTX uremic animals, hyperlipoproteinemia is less marked than in PT-intact uremic animals, but serum lipids are still higher in PTX uremic animals than in nonuremic PT-intact animals. This would indicate that hyperlipemia is caused by PTH-independent mechanisms but is intensified by the presence of secondary hyperparathyroidism. The role of PTH in the hyperlipoproteinemia of uremic patients has not been clarified so far.
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PMID:Does parathyroid hormone play a role in lipid metabolism? 699 9

Iliac crest biopsies of normals, uremic patients and subjects with primary hyperparathyroidism (pHPT) were investigated. It appeared that serum 1,25- and 24,25-(OH)2-D3 correlated inversely with basal adenylate cyclase (AC) activity and relative PTH-stimulated AC, respectively. Net PTH-elicited AC (dPTH-AC) activation hence reflected individual vitamin D status. The combination variable serum PTH (s-PTH) x dPTH-AC x [H+] correlated well with resorption surface (RS) in both normals, patients with pHPT or subjects with uremia, while s-PTH, dPTH-AC activity or pH as single variables were only marginally related to RS. For all subjects analyzed, osteoid volume (OV) correlated positively with serum alkaline phosphatase but negatively with serum 1,25-(OH)2-D3. OV showed no correlation with dPTH-AC, while the relationship between OV and s-PTH was strong, suggesting that PTH stimulates osteoid deposition via some signalling pathway other than cAMP. In normals, OV was inversely proportional to s-PTH, due to homologous desensitization of this signalling system. Furthermore, s-PTH was negatively correlated with urine cAMP due to homologous desensitization of the effect of PTH on the kidney 25-(OH)-D3 1 alpha-hydroxylase. This phenomenon was absent in uremic patients. Evaluation of variables by artificial intelligence showed that the prototype uremic patient exhibited serum creatinine > 900 microM, RS > 0.12, pH between 7.15 and 7.34 and s-PTH x dPTH-AC x [H+] between 0.5 and 3.7 units with the distinguishability index 'very good' (< 5% overlap) towards normals. Average similarity of uremic patients with the prototype for normal subjects was only 22%. Cluster analysis of all the variables was conducted for comparison and yielded less clinically relevant information. Hence, emulation done by the expert system was superior and clearly indicates that present treatment modalities restore normal bone turnover only to a minor degree or not at all.
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PMID:PTH-stimulated adenylate cyclase activity and bone histomorphometry in iliac crest biopsies in the evaluation of uremic patients: a pilot study with the use of artificial intelligence. 816 16

Parathyroid hormone (PTH) is secreted from the parathyroid glands in response to low plasma calcium levels. Besides its classical actions on bone and kidney, PTH may have other important effects, including metabolic effects, as suggested for instance by increased prevalence of insulin resistance and type 2 diabetes in patients with primary hyperparathyroidism. Moreover, secondary hyperparathyroidism may contribute to the metabolic derangements that characterize states of vitamin D deficiency. PTH has been shown to induce adipose tissue lipolysis, but the details of the lipolytic action of PTH have not been described. Here we used primary mouse adipocytes to show that intact PTH (1-84) as well as the N-terminal fragment (1-37) acutely stimulated lipolysis in a dose-dependent manner, whereas the C-terminal fragment (38-84) was without lipolytic effect. The lipolytic action of PTH was paralleled by phosphorylation of known protein kinase A (PKA) substrates, i.e. hormone-sensitive lipase (HSL) and perilipin. The phosphorylation of HSL in response to PTH occurred at the known PKA sites S563 and S660, but not at the non-PKA site S565. PTH-induced lipolysis, as well as phosphorylation of HSL at S563 and S660, was blocked by both the PKA-inhibitor H89 and the adenylate cyclase inhibitor MDL-12330A, whereas inhibitors of extracellular-regulated kinase (ERK), protein kinase B (PKB), AMP-activated protein kinase (AMPK) and Ca(2+)/calmodulin-dependent protein kinase (CaMK) had little or no effect. Inhibition of phosphodiesterase 4 (PDE4) strongly potentiated the lipolytic action of PTH, whereas inhibition of PDE3 had no effect. Our results show that the lipolytic action of PTH is mediated by the PKA signaling pathway with no or minor contribution of other signaling pathways and, furthermore, that the lipolytic action of PTH is limited by simultaneous activation of PDE4. Knowledge of the signaling pathways involved in the lipolytic action of PTH is important for our understanding of how metabolic derangements develop in states of hyperparathyroidism, including vitamin D deficiency.
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PMID:Parathyroid hormone induces adipocyte lipolysis via PKA-mediated phosphorylation of hormone-sensitive lipase. 2672 18