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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
Gene Review

HPT  -  hypoparathyroidism

Homo sapiens

Synonyms: HPTX, HYPX
 
 
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Disease relevance of HPT

  • To address this issue in humans, bone biopsy specimen samples from 9 normal controls and 16 patients with moderate to severe secondary renal hyperparathyroid bone disease (2 degrees HPT) with elevated PTH levels were studied to determine whether osteoclasts in the bone microenvironment express PTH-1R messenger RNA (mRNA) and protein [1].
  • Recently, we presented evidence for aberrant accumulation of non-phosphorylated (stabilized) beta-catenin in benign parathyroid tumors from patients with primary hyperparathyroidism (pHPT) or HPT secondary to uremia (sHPT) [2].
  • The condensed recombinant retroviruses were extracted and used to infect HSCs, which were injected into mice suffering from HPT [3].
  • Single specimens from normal subjects and from individuals with primary hyperparathyroidism, hypercalcemia associated with malignancy, and hypoparathyroidism were analyzed with all three methods [4].
  • BACKGROUND: Hypoparathyroidism with permanent hypocalcemia is a well-recognized complication after thyroid surgery [5].
 

Psychiatry related information on HPT

 

High impact information on HPT

 

Chemical compound and disease context of HPT

 

Biological context of HPT

  • Our results established linkage (lod score > 3) between HPT and eight of these 12 loci and indicated that the most likely location of HPT was within a 1.5 Mb interval flanked centromerically by F9 and telomerically by DXS984 [20].
  • Thus, the results of this study have helped to refine the map location of HPT, and this will facilitate the identification of this putative developmental gene and its role in the embryological formation of the parathyroids [20].
  • We aimed to examine the role of DXA in assessing variation in size-adjusted bone mineral content (BMC) in children with CRI and compare it with a cohort with hypoparathyroidism (HPT) and pseudo-hypoparathyroidism (PHPIa) [21].
  • Phosphaturic responses (expressed as % decrease in TmPO4/glomerular filtration rate) were lower (p = 0.013) in the PsH type I (28.8 +/- 3.75) compared with those of the HP patients (43 +/- 3.48) [22].
  • Thus, our analysis of idiopathic hypoparathyroidism reveals genetic heterogeneity for this disorder [23].
 

Anatomical context of HPT

 

Associations of HPT with chemical compounds

  • Infusion of PTH to 3 children with hypoparathyroidism produced exaggerated cyclic AMP, phosphate, calcium, potassium, and bicarbonate responses [27].
  • It is suggested that 1,25(OH)2D production by PTH is intact in HP, but is impaired in PHP mainly due to a defect in the activation of adenylate cyclase system [15].
  • Thus, treatment with either CaCO3 or sevelamer resulted in equivalent control of the biochemical and skeletal lesions of 2 degrees HPT [28].
  • This study was undertaken to compare the biochemical and skeletal responses to thrice weekly intraperitoneal (i.p.) versus oral doses of calcitriol in children with secondary HPT undergoing peritoneal dialysis (CCPD) [29].
  • RESULTS: Compared with control treatment, cinacalcet improved the management of secondary HPT [30].
 

Regulatory relationships of HPT

 

Other interactions of HPT

  • In order to define further the map location of HPT and thereby facilitate its isolation, we have undertaken linkage studies using polymorphic loci whose order has been established as Xcen - DXS1001 - DXS294 - DXS102 - F9 - DXS1232 - DXS984 - CDR1 - DXS105 - DXS1205 - DXS1227 - DXS98 - DXS52 - Xqter, within this region [20].
  • X linked recessive idiopathic hypoparathyroidism (HPT) has been observed in two kindreds from Missouri, USA [20].
  • We hypothesized that the cytokines increase CASR expression and reduce the set point for parathyroid hormone suppression by extracellular calcium, leading to hypocalcemia and hypoparathyroidism [34].
  • Serum FGF-23 regulation was studied in patients with hypoparathyroidism or pseudohypoparathyroidism treated with calcitriol [35].
  • PTH produced a rise in serum PRL in the normal subjects from 5.1 +/- 0.8 ng/ml (SE) to 14.9 +/- 3.0 ng/ml (P less than 0.01), while levels similarly rose from 4.0 +/- 0.2 to 8.5 +/- 0.8 ng/ml (P less than 0.01) in the patients with hypoparathyroidism [36].
 

Analytical, diagnostic and therapeutic context of HPT

References

  1. Parathyroid hormone/parathyroid hormone-related peptide type 1 receptor in human bone. Langub, M.C., Monier-Faugere, M.C., Qi, Q., Geng, Z., Koszewski, N.J., Malluche, H.H. J. Bone Miner. Res. (2001) [Pubmed]
  2. Activated beta-catenin in the novel human parathyroid tumor cell line sHPT-1. Bj??rklund, P., Kerstr??m, G., Westin, G. Biochem. Biophys. Res. Commun. (2007) [Pubmed]
  3. Optimising gene therapy of hypoparathyroidism with hematopoietic stem cells. Zhou, Y., Lü, B.J., Xu, P., Song, C.F. Chin. Med. J. (2005) [Pubmed]
  4. Immunochemiluminometric and immunoradiometric determinations of intact and total immunoreactive parathyrin: performance in the differential diagnosis of hypercalcemia and hypoparathyroidism. Endres, D.B., Villanueva, R., Sharp, C.F., Singer, F.R. Clin. Chem. (1991) [Pubmed]
  5. Assessment of parathyroid autotransplantation for preservation of parathyroid function after total thyroidectomy. El-Sharaky, M.I., Kahalil, M.R., Sharaky, O., Sakr, M.F., Fadaly, G.A., El-Hammadi, H.A., Moussa, M.M. Head & neck. (2003) [Pubmed]
  6. Profile of a clinical practice: Thresholds for surgery and surgical outcomes for patients with primary hyperparathyroidism: a national survey of endocrine surgeons. Sosa, J.A., Powe, N.R., Levine, M.A., Udelsman, R., Zeiger, M.A. J. Clin. Endocrinol. Metab. (1998) [Pubmed]
  7. Autosomal dominant hypoparathyroidism with variable, age-dependent severity. Winter, W.E., Silverstein, J.H., Maclaren, N.K., Riley, W.J., Chiaro, J.J. J. Pediatr. (1983) [Pubmed]
  8. Hypercalcemia due to ectopic secretion of parathyroid related protein from pancreatic carcinoma: a case report. Cavestro, G.M., Mantovani, N., Coruzzi, P., Nouvenne, A., Marcucci, F., Franzè, A., Di Mario, F., Okolicsanyi, L. Acta bio-medica de L'Ateneo parmense : organo della Società di medicina e scienze naturali di Parma. (2002) [Pubmed]
  9. A new point mutation associated with mitochondrial encephalomyopathy. Morten, K.J., Cooper, J.M., Brown, G.K., Lake, B.D., Pike, D., Poulton, J. Hum. Mol. Genet. (1993) [Pubmed]
  10. antiphospholipid antibodies syndrome associated with hyperhomocysteinemia related to MTHFR Gene C677T and A1298C heterozygous mutations in a young man with idiopathic hypoparathyroidism (DiGeorge syndrome). Nucera, C., Vaccaro, M., Moleti, M., Priolo, C., Tortorella, G., Angioni, A., Ientile, R., Violi, M.A., Loda, M., Trimarchi, F., Vermiglio, F. J. Clin. Endocrinol. Metab. (2006) [Pubmed]
  11. A familial syndrome of hypocalcemia with hypercalciuria due to mutations in the calcium-sensing receptor. Pearce, S.H., Williamson, C., Kifor, O., Bai, M., Coulthard, M.G., Davies, M., Lewis-Barned, N., McCredie, D., Powell, H., Kendall-Taylor, P., Brown, E.M., Thakker, R.V. N. Engl. J. Med. (1996) [Pubmed]
  12. Brief report: autosomal dominant familial hypoparathyroidism, sensorineural deafness, and renal dysplasia. Bilous, R.W., Murty, G., Parkinson, D.B., Thakker, R.V., Coulthard, M.G., Burn, J., Mathias, D., Kendall-Taylor, P. N. Engl. J. Med. (1992) [Pubmed]
  13. Clinical variation of autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) in a series of 68 patients. Ahonen, P., Myllärniemi, S., Sipilä, I., Perheentupa, J. N. Engl. J. Med. (1990) [Pubmed]
  14. Hypoparathyroidism and the DiGeorge syndrome. Greenberg, F. N. Engl. J. Med. (1989) [Pubmed]
  15. Stimulation of 1,25-dihydroxyvitamin D production by parathyroid hormone and dibutyryl 3',5'-cyclic AMP in normal subjects, hypoparathyroidism and pseudohypoparathyroidism. Unakami, H., Furukawa, Y., Sohn, H.E., Yumita, S., Miura, R., Hanew, K., Yoshinaga, K. Tohoku J. Exp. Med. (1982) [Pubmed]
  16. Hypoparathyroidism during alpha-INF therapy in a patient with multiple myeloma. Ueki, K., Tsuchida, A., Murakami, H., Yano, S., Kobayashi, N., Omine, M., Naruse, T. Journal of medicine. (1989) [Pubmed]
  17. Increased catabolism of 25-hydroxyvitamin D in patients with partial gastrectomy and elevated 1,25-dihydroxyvitamin D levels. Implications for metabolic bone disease. Davies, M., Heys, S.E., Selby, P.L., Berry, J.L., Mawer, E.B. J. Clin. Endocrinol. Metab. (1997) [Pubmed]
  18. Intravenous calcitriol for treatment of hyperparathyroidism in children on hemodialysis. Greenbaum, L.A., Grenda, R., Qiu, P., Restaino, I., Wojtak, A., Paredes, A., Benador, N., Melnick, J.Z., Williams, L.A., Salusky, I.B. Pediatr. Nephrol. (2005) [Pubmed]
  19. Urinary cyclic 3',5'-adenosine monophosphate responses to exogenous and endogenous parathyroid hormone in familial benign hypercalcemia and primary hyperparathyroidism. Heath, H., Purnell, D.C. J. Lab. Clin. Med. (1980) [Pubmed]
  20. Localisation of X linked recessive idiopathic hypoparathyroidism to a 1.5 Mb region on Xq26-q27. Trump, D., Dixon, P.H., Mumm, S., Wooding, C., Davies, K.E., Schlessinger, D., Whyte, M.P., Thakker, R.V. J. Med. Genet. (1998) [Pubmed]
  21. Bone mineral content, corrected for height or bone area, measured by DXA is not reduced in children with chronic renal disease or in hypoparathyroidism. Ahmed, S.F., Russell, S., Rashid, R., Beattie, T.J., Murphy, A.V., Ramage, I.J., Maxwell, H. Pediatr. Nephrol. (2005) [Pubmed]
  22. The renal response to exogenous parathyroid hormone in treated pseudohypoparathyroidism. Stone, M.D., Hosking, D.J., Garcia-Himmelstine, C., White, D.A., Rosenblum, D., Worth, H.G. Bone (1993) [Pubmed]
  23. Parathyroid hormone gene analysis in autosomal hypoparathyroidism using an intragenic tetranucleotide (AAAT)n polymorphism. Parkinson, D.B., Shaw, N.J., Himsworth, R.L., Thakker, R.V. Hum. Genet. (1993) [Pubmed]
  24. Long-term prognosis of parathyroid function after successful percutaneous ethanol injection therapy (PEIT) guided by color Doppler flow mapping in chronic dialysis patients. Kakuta, T., Kunimatsu, K., Tadaki, F., Fujisaki, T., Noguchi, M., Abe, Y., Sakai, H., Kurokawa, K., Saito, A. Biomed. Pharmacother. (2000) [Pubmed]
  25. Parathyroid hormone responsiveness in hypoparathyroidism with hypomagnesemia. Michelis, M.F., Bragdon, R.W., Fusco, R.D., Eichenholz, A., Davis, B.B. Am. J. Med. Sci. (1975) [Pubmed]
  26. Human chorionic gonadotropin subunit measurement in primary hyperparathyroidism. Stock, J.L., Weintraub, B.D., Rosen, S.W., Aurbach, G.D., Spiegel, A.M., Marx, S.J. J. Clin. Endocrinol. Metab. (1982) [Pubmed]
  27. Parathyroid hormone infusion test in children and adolescents. Hochberg, Z., Moses, A.M., Richman, R.A. Mineral and electrolyte metabolism. (1984) [Pubmed]
  28. Sevelamer controls parathyroid hormone-induced bone disease as efficiently as calcium carbonate without increasing serum calcium levels during therapy with active vitamin D sterols. Salusky, I.B., Goodman, W.G., Sahney, S., Gales, B., Perilloux, A., Wang, H.J., Elashoff, R.M., Jüppner, H. J. Am. Soc. Nephrol. (2005) [Pubmed]
  29. Intermittent calcitriol therapy in secondary hyperparathyroidism: a comparison between oral and intraperitoneal administration. Salusky, I.B., Kuizon, B.D., Belin, T.R., Ramirez, J.A., Gales, B., Segre, G.V., Goodman, W.G. Kidney Int. (1998) [Pubmed]
  30. First- and second-generation immunometric PTH assays during treatment of hyperparathyroidism with cinacalcet HCl. Martin, K.J., Jüppner, H., Sherrard, D.J., Goodman, W.G., Kaplan, M.R., Nassar, G., Campbell, P., Curzi, M., Charytan, C., McCary, L.C., Guo, M.D., Turner, S.A., Bushinsky, D.A. Kidney Int. (2005) [Pubmed]
  31. Increased renal responses to exogenous parathyroid hormone in postsurgical hypoparathyroidism. Law, W.M., Heath, H. J. Clin. Endocrinol. Metab. (1984) [Pubmed]
  32. Hypoparathyroidism-induced epilepsy: an overlooked cause. Su, Y.C., Lin, Y.M., Hou, S.W., Chen, C.C., Chong, C.F., Wang, T.L. The American journal of emergency medicine. (2006) [Pubmed]
  33. Hypocalcemic cardiomyopathy in a patient with idiopathic hypoparathyroidism. Kudoh, C., Tanaka, S., Marusaki, S., Takahashi, N., Miyazaki, Y., Yoshioka, N., Hayashi, M., Shimamoto, K., Kikuchi, K., Iimura, O. Intern. Med. (1992) [Pubmed]
  34. Calcium-sensing receptor gene transcription is up-regulated by the proinflammatory cytokine, interleukin-1beta. Role of the NF-kappaB PATHWAY and kappaB elements. Canaff, L., Hendy, G.N. J. Biol. Chem. (2005) [Pubmed]
  35. Fibroblast growth factor-23 is regulated by 1alpha,25-dihydroxyvitamin D. Collins, M.T., Lindsay, J.R., Jain, A., Kelly, M.H., Cutler, C.M., Weinstein, L.S., Liu, J., Fedarko, N.S., Winer, K.K. J. Bone Miner. Res. (2005) [Pubmed]
  36. Prolactin and calcitonin responses to parathyroid hormone infusion in hypoparathyroid, pseudohypoparathyroid, and normal subjects. Brickman, A.S., Carlson, H.E., Deftos, L.J. J. Clin. Endocrinol. Metab. (1981) [Pubmed]
  37. Effects of an excess and a deficiency of endogenous parathyroid hormone on volumetric bone mineral density and bone geometry determined by peripheral quantitative computed tomography in female subjects. Chen, Q., Kaji, H., Iu, M.F., Nomura, R., Sowa, H., Yamauchi, M., Tsukamoto, T., Sugimoto, T., Chihara, K. J. Clin. Endocrinol. Metab. (2003) [Pubmed]
  38. Serum magnesium concentration is an independent predictor of parathyroid hormone levels in peritoneal dialysis patients. Navarro, J.F., Mora, C., Macia, M., Garcia, J. Peritoneal dialysis international : journal of the International Society for Peritoneal Dialysis. (1999) [Pubmed]
 
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