Disease relevance of HRPT1

• A mouse model of human familial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism [1].
• This study examined the hypothesis that altered binding of 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) to parathyroid receptors might be involved in the pathogenesis of secondary hyperparathyroidism associated with chronic renal failure [2].
• Recurrent hyperparathyroidism from an autotransplanted parathyroid adenoma [3].
• Most cases of primary hyperparathyroidism are associated with enlargement of a single gland (i.e., an "adenoma") or with chief-cell hyperplasia, but there is controversy about the relative frequency of each of these entities [4].
• Studies were done to determine the cause for hypocalcemia, secondary hyperparathyroidism, osteomalacia and osteitis fibrosa cystica in a 22-year-old black woman [5].

Psychiatry related information on HRPT1

• Eleven patients with hypothyroidism, metabolic encephalopathies due to hyponatremia, hyperparathyroidism, and hypoglycemia required laboratory tests for diagnosis, whereas the other dementia diagnoses were made primarily on the basis of data available on the history and physical and neurologic examinations [6].
• In consecutively referred patients with primary hyperparathyroidism, psychiatric disturbances of mainly a depressive character were found upon detailed analysis within a majority of the patients, and parathyroid surgery resulted in a clear improvement in mental health [7].
• In addition to weight and physical activity, the presence of mild hyperparathyroidism was associated with a low BMD of the lumbar spine (P = 0.0062) and the femoral neck (P = 0.0250), and a low calcium intake was associated with a low BMD of the femoral neck (P = 0.0044) [8].
• Intracranial calcification in hyperparathyroidism associated with gait apraxia and parkinsonism [9].
• We describe a patient who presented with secondary hyperparathyroidism and symptoms of memory loss, pruritus, constipation, and bone and joint pain [10].

High impact information on HRPT1

• HRPT2, encoding parafibromin, is mutated in hyperparathyroidism-jaw tumor syndrome [11].
• CONCLUSIONS: In patients with primary hyperparathyroidism, parathyroidectomy results in the normalization of biochemical values and increased bone mineral density [12].
• METHODS: We studied 134 consecutive patients with chronic pancreatitis (alcohol-related disease in 71, hyperparathyroidism in 2, hypertriglyceridemia in 1, and idiopathic disease in 60) [13].
• CONCLUSIONS: The calcimimetic drug R-568 reduces serum parathyroid hormone and ionized calcium concentrations in postmenopausal women with primary hyperparathyroidism [14].
• Primary hyperparathyroidism is a common disorder with an annual incidence of approximately 0.5 in 1,000 (ref. 1). In more than 95% of cases, the disease is caused by sporadic parathyroid adenoma or sporadic hyperplasia [15].

Chemical compound and disease context of HRPT1

• To evaluate the role of serum calcium in human insulin secretion, insulin responses after a 100-g oral glucose load were studied in nine patients with primary hyperparathyroidism, five with idiopathic hypoparathyroidism, three with pseudohypoparathyroidism and one with normocalcemic secondary hyperparathyroidism [16].
• Vitamin D3, 4000 units per day for four weeks, increased the serum 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D to as high as 29 and 297 pg per milliliter, respectively, and corrected the hypocalcemia and secondary hyperparathyroidism [5].
• Other causes were as follows: diuretics, hyperalimentation, alcoholism, respiratory alkalosis, dialysis, insulin, corticosteroids, diabetic ketoacidosis, vomiting, phosphate-binding antacid, Gram-negative sepsis, primary hyperparathyroidism, saline, epinephrine, gastrointestinal malabsorption, and unknown [17].
• Estrogen deficiency is known to play a critical role in the development of osteoporosis, while calcium and vitamin D deficiencies and secondary hyperparathyroidism also contribute [18].
• Serum bone gamma-carboxyglutamic acid-containing (Gla) protein (sBGP), a sensitive and specific marker of bone turnover, was measured in 25 patients with primary hyperparathyroidism and in 24 patients with bone metastases with or without hypercalcemia [19].

Biological context of HRPT1

• Coinheritance of either neonatal severe hyperparathyroidism or sucrase-isomaltase deficiency and alkaptonuria provided a candidate location for the mutated genes on chromosome 3 [20].
• In some patients with chronic renal failure, bone mineralization becomes defective after parathyroidectomy for secondary hyperparathyroidism [21].
• In patients with uremia, the dose of erythropoietin needed to achieve an adequate hematocrit response may depend on the severity of secondary hyperparathyroidism and the extent of bone marrow fibrosis [22].
• Impaired effects of active vitamin D3 may contribute to the relatively enhanced secretion and cell proliferation seen in hyperparathyroidism (HPT) [23].
• Vitamin D receptor genotypes in primary hyperparathyroidism [23].

Anatomical context of HRPT1

• Of the patients, 98 had recurrent, "idiopathic" kidney stones, 8 had primary hyperparathyroidism, 7 had renal or urinary tract malformations, and 1 had primary hyperoxaluria [24].
• Multiple endocrine neoplasia type 2A (MEN2A) is an autosomal dominantly inherited cancer syndrome characterized by medullary carcinoma of the thyroid, phaeochromocytoma and hyperparathyroidism [25].
• A case of familial primary hyperparathyroidism occurred in which persistent hypercalcemia was caused by hyperplastic parathyroid tissue left in the neck and mediastinum after initial surgery and by a hyperfunctioning parathyroid autograft in the forearm [26].
• Erythrocyte survival in chronic renal failure. Role of secondary hyperparathyroidism [27].
• INTERPRETATION: Simultaneous recording of 99mTc-sestamibi and 123I improved the imaging of parathyroid glands in secondary hyperparathyroidism [28].

Associations of HRPT1 with chemical compounds

• The importance of circulating 1,25-dihydroxyvitamin D in the pathogenesis of hypercalciuria and renal-stone formation in primary hyperparathyroidism [29].
• Cimetidine and hyperparathyroidism [30].
• Urinary cyclic AMP during surgery for primary hyperparathyroidism [31].
• Is estrogen preferable to surgery for postmenopausal women with primary hyperparathyroidism [32]?
• Influence of furosemide on parathyroid hormone levels in hyperparathyroidism [33].

Physical interactions of HRPT1

• The diagnosis of primary hyperparathyroidism has rested on the finding of hypercalcemia coupled with an elevated serum parathyroid hormone (PTH) level [34].
• One further conclusion is that hypergastrinemia in patients with renal failure is the result of the combined effects of the reduced catabolism of gastrin in the kidney and its increased synthesis which is for the most part connected with hypochlohydria and secondary hyperparathyroidism [35].

Enzymatic interactions of HRPT1

• Four small families with a family history of hyperparathyroidism without clear-cut MEN-1 features were screened for a MEN1 mutation [36].

Regulatory relationships of HRPT1

• Addition of TGF-beta to parathyroid cells from patients with secondary hyperparathyroidism inhibited their proliferation and PTH secretion [37].
• It is unclear whether the mutant PHEX gene can induce hyperparathyroidism by abnormal regulation of peptidases [38].
• RESULTS: Vasodilatation of arterial segments produced by both PTH 20 nmol l(-1) and PTHrP 100 nmol l(-1) did not differ significantly between control and hyperparathyroidism groups (P > 0.08, Mann-Whitney U test) [39].
• CONCLUSIONS: GCMB expression is upregulated in abnormal parathyroid glands of hyperparathyroidism and decreases in response to hypocalcemia [40].
• These findings indicate that MEN1 gene mutations contributed to tumorigenesis of the right upper parathyroid gland in this case of phosphate-induced tertiary hyperparathyroidism [41].

Other interactions of HRPT1

• RESULTS: There was no difference in the activities of IMPDH and salvage pathway enzymes GPRT and HRPT as well as in intracellular GTP and ATP concentrations between the patients before switch to MMF and healthy controls [42].
• 7 patients with malignant disease had PTH concentrations above 4.0 pmol/l, consistent with coexisting primary hyperparathyroidism [43].
• Plasma PTHrP was detectable in 35 (88%) of 40 patients with solid tumours and 3 of 9 patients with haematological malignant disease; it was undetectable in 92% of patients with primary hyperparathyroidism [43].
• We now show that the pathogenesis of MEN1-associated parathyroid lesions involves unmasking of a recessive mutation at the disease locus and that sporadic primary hyperparathyroidism shares the same mechanisms [44].
• Familial isolated hyperparathyroidism is rarely caused by germline mutation in HRPT2, the gene for the hyperparathyroidism-jaw tumor syndrome [45].

Analytical, diagnostic and therapeutic context of HRPT1

• This method of treatment offers a suitable alternative to radical subtotal parathyroidectomy in selected patients with hyperparathyroidism [46].
• We examined the relation between the erythropoietic response to erythropoietin and hyperparathyroidism in a cross-sectional study of 18 patients undergoing hemodialysis who had received erythropoietin therapy for one to three years [22].
• We compared the effect of oral administration of 25-OH-D3 (50 micrograms per day for one month) on serum concentrations of calcium, phosphate, parathyroid hormone, 25-OH-D, and 1,25-(OH)2D in five healthy adults and in six patients with primary hyperparathyroidism [47].
• The response to phototherapy was unaffected by the presence of secondary hyperparathyroidism [48].
• Persistent hyperparathyroidism caused by incomplete parathyroid resection and a hyperfunctioning parathyroid autograft [26].

References