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

• A 1991 NIH Consensus Development Conference statement provided recommendations for the management of patients with asymptomatic and minimally symptomatic primary hyperparathyroidism (primary HPT), but adherence to these guidelines has not been documented [6].
• None of the four affected adults has had major complications of hypoparathyroidism (mental retardation, cataracts, or seizures) [7].
• This case is a report of a male, 52 year old, heavy smoker, with a history of about 10 years of alcohol abuse (he quitted in 1993), gastric resection for ulcer (Billroth II 1970), hypoparathyroidism and macroamylasemia, died for undiagnosed pancreatic carcinoma revealed at necroscopy [8].
• We describe a further mutation in tRNA leucine(UUR) in a patient with mitochondrial encephalomyopathy, pigmentary retinopathy, dementia, hypoparathyroidism and diabetes mellitus [9].
• DATA ACQUISITION: In this report, we present the case of a 19-yr-old patient with a past medical history of learning disability and obesity affected with idiopathic hypoparathyroidism, metabolic syndrome, and diffuse vasculitis disorders [10].

High impact information on HPT

• METHODS: We studied six kindreds given a diagnosis of autosomal dominant hypoparathyroidism on the basis of their hypocalcemia and normal serum parathyroid hormone concentrations, a combination that suggested a defect of the calcium-sensing receptor [11].
• CONCLUSIONS: Gain-of-function mutations in the calcium-sensing receptor are associated with a familial syndrome of hypocalcemia with hypercalciuria that needs to be distinguished from hypoparathyroidism [11].
• Brief report: autosomal dominant familial hypoparathyroidism, sensorineural deafness, and renal dysplasia [12].
• Dental-enamel hypoplasia and keratopathy were also frequent but were not attributable to hypoparathyroidism [13].
• Hypoparathyroidism and the DiGeorge syndrome [14].

Chemical compound and disease context of HPT

• Stimulation of 1,25-dihydroxyvitamin D production by parathyroid hormone and dibutyryl 3',5'-cyclic AMP in normal subjects, hypoparathyroidism and pseudohypoparathyroidism [15].
• A 66 year-old woman with multiple myeloma developed hypoparathyroidism during combination chemotherapy with melphalan, prednisolone, and alpha-interferon (INF) [16].
• Patients with PGX and evidence of 2 degrees HPT with elevated 1,25-(OH)2D have a reduced t1/2 [3H]25OHD3, and this may explain the increased susceptibility of the subjects to osteomalacia [17].
• This double-blind, placebo-controlled study evaluated the safety and efficacy of intravenous (i.v.) calcitriol (Calcijex) for treatment of secondary hyperparathyroidism (secondary HPT) in pediatric end-stage renal disease (ESRD) patients on hemodialysis (HD) [18].
• EDTA-induced hypocalcemia raised serum iPTH and UcAMP in all three groups; the increases of iPTH (two assays of differing specificity) were greatest in 1 omicron HPT and least in FBH [19].

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

• Approximately half of osteoclasts found in bone of patients with 2 degrees HPT have the PTH-1R protein [1].
• This research examines the usefulness of selective percutaneous ethanol injection therapy (PEIT) of parathyroid glands in order to treat and control for 2 HPT [24].
• This study was designed to optimize the gene therapy of HPT with hematopoietic stem cells (HSCs) recombined with the parathyroid hormone (PTH) gene [3].
• A patient with hypoparathyroidism and a markedly decreased serum concentration of magnesium (0.7 mEq/liter), but a normal red blood cell magnesium level, is described who increased serum calcium concentration and decreased per cent renal tubular reabsorption of phosphate when parathyroid extract was given [25].
• Thus, in patients with 1 degrees HPT, determination of subunits of hCG may be helpful in making the diagnosis of parathyroid carcinoma or in screening for associated (and probably malignant) pancreatic islet disease [26].

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

• These data and others from the literature suggest that chronic hypoparathyroidism enhances renal responses to PTH, consistent with the concept of hormonal regulation of tissue sensitivity to the hormone [31].
• Hypoparathyroidism-induced epilepsy: an overlooked cause [32].
• An idiopathic hypoparathyroidism-induced cardiomyopathy patient had severe long-lasting hypocalcemia [33].

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

• In conclusion, selective PEIT appears to be able to control appropriate parathyroid function and to be the method of choice to treat 2 HPT prior to parathyroidectomy [24].
• This method has provided theoretical evidence for the clinical gene therapy of HPT [3].
• Lumbar BMD by dual-energy x-ray absorptiometry was higher in the order: hypo > cont = hyper, and radius-1/3 BMD was significantly higher in the order: hypo > cont > hyper [37].
• Immunochemiluminometric and immunoradiometric determinations of intact and total immunoreactive parathyrin: performance in the differential diagnosis of hypercalcemia and hypoparathyroidism [4].
• CONCLUSIONS: Hypermagnesemia and hypoparathyroidism are frequent in CAPD patients [38].

References