Disease relevance of PHPT1

• A subset of families are likely to be genetic variants of other familial tumour syndromes in which PHPT is the main feature, for example multiple endocrine neoplasia type 1 (MEN 1) and the hyperparathyroidism-jaw tumour syndrome (HPT-JT) [1].
• Medical treatment is debatable under other circumstances: mild chronic hypercalcemia, patients who refuse surgery, serious coexisting medical problems and recurrence or persistence of PHPT after surgical treatment [2].
• Both in primary (PHPT) and secondary hyperparathyroidism (SHPT) PTH excess is thought to be involved in deteriorating insulin sensitivity and secretion though their different clinical and pathophysiological conditions [3].
• In PHPT these abnormalities are related to a high frequency of Type 2 diabetes mellitus and also impaired glucose tolerance according to recent clinical studies, without differences between symptomatic and asymptomatic clinical presentation [3].
• Video-assisted neck exploration was conducted in all cases under general anaesthesia leading to a partial or total thyroidectomy, and to a selective adenoma removal in PHPT or to a subtotal parathyroid resection in SHPT [4].

High impact information on PHPT1

• The structure of phosphohistidine phosphatase (PHPT1), the first identified eukaryotic-protein histidine phosphatase, has been determined to a resolution of 1.9A using multiple-wavelength anomalous dispersion methods [5].
• Bone density, serum calcium concentration, and/or urinary calcium excretion per se can show evidence for progression in as many as 25% of patients with asymptomatic PHPT [6].
• The bone formation rate was significantly higher in PHPT than in either OP or N, and not different between OP and N [7].
• These findings suggest that mild PHPT protects against the loss of cancellous bone structure that normally follows menopause [7].
• Global gene expression profiling has been used to study the molecular mechanisms of increased bone remodeling caused by PHPT [8].

Chemical compound and disease context of PHPT1

• The PHPT patients who died differed from the whole PHPT material in higher mean age at operation (61 years v. 53 years), higher preoperative serum calcium values (3.31 mmol/l v. 3.08 mmol/l), more frequently elevated serum creatine preoperatively (44% v. 17%) and higher mean weight of the removed adenomas (3300 mg v. 2000 mg) [9].

Biological context of PHPT1

• These results will facilitate future studies of the reaction mechanism, substrate binding, and molecular structure of the phosphohistidine phosphatase [10].
• Molecular cloning from a human embryonic kidney cell cDNA-library followed by expression and purification, yielded a protein with a molecular mass of 13 700 Da, and an EDTA-insensitive phosphohistidine phosphatase activity of 9 micro mol.min-1.mg-1 towards phosphopeptide I [11].
• In the present work, we have searched for potential active site residues in the human phosphohistidine phosphatase by point mutations of conserved histidine and arginine residues to alanine [10].
• This short review of the clinical and pathophysiological data of literature on glucose homeostasis disorders in hyperparathyroidism focuses on its potential clinical and therapeutic impact, particularly in the management of PHPT [3].

Anatomical context of PHPT1

• Northern blot analysis indicated that the human phosphohistidine phosphatase mRNA was present preferentially in heart and skeletal muscle [11].
• Six PHPT patients, but none of the controls, had had a differentiated non-medullary thyroid carcinoma [12].
• Recurring urinary tract infections occurred as often in both groups, though renal stones had naturally been more frequent in the PHPT group [12].

Associations of PHPT1 with chemical compounds

• Recently, a few reports have appeared on a mammalian 14-kDa phosphohistidine phosphatase, also named protein histidine phosphatase [10].
• Serum creatinine was elevated in 33 PHPT patients and in 9 controls (p less than 0.001), and renal damage was also more severe in the PHPT patients [12].

Analytical, diagnostic and therapeutic context of PHPT1

• For these reasons, parathyroidectomy should generally be recommended for patients with a secure diagnosis of PHPT, even in the absence of classical symptoms [13].
• We analyzed mRNAs in transiliacal bone biopsies from 7 patients with PHPT using Affymetrix HG-U133A Gene Chips containing more than 22000 different probe sets [8].
• The prevalence of PHPT in the control group was 1.25% [12].
• In all cases, video-assisted neck exploration was performed under general anesthesia, leading to selective adenoma removal in PHPT or subtotal parathyroid resection in SHPT [14].
• METHODS: Twenty-two patients aged 70 years and over with biochemically proven PHPT and with a single parathyroid adenoma identified by localization studies (sestamibi SPECT scan and ultrasonography) underwent 23 operations over 29 months (out of a total of 140 patients operated upon during the same period) [15].

References