Disease relevance of Hyperparathyroidism

• We demonstrate that mutations in the human Ca(2+)-sensing receptor gene cause familial hypocalciuric hypercalcemia (FHH) and neonatal severe hyperparathyroidism (NSHPT), two inherited conditions characterized by altered calcium homeostasis [1].
• The results indicate that hyperparathyroidism and hypocalcemia induced by the low calcium diet attenuated the hypotensive response to parathyroid hormone compared with responses in rats raised on a 1.4% calcium diet [2].
• In addition, families with isolated endocrine neoplasia, notably familial isolated hyperparathyroidism (FIHP) and familial acromegaly, have also been reported [3].
• Normalization of mineral ion homeostasis by dietary means prevents hyperparathyroidism, rickets, and osteomalacia, but not alopecia in vitamin D receptor-ablated mice [4].
• Uremia is associated with hyperparathyroidism and PTH affects muscle metabolism; PTH enhances muscle proteolysis and impairs muscle bioenergetics, and it is possible that PTH also affects fatty acids oxidation [5].

High impact information on Hyperparathyroidism

• Superimposed Gcm2 deficiency rescued the perinatal lethality in CasR-deficient mice in association with ablation of the parathyroid glands and correction of the severe hyperparathyroidism [6].
• Mice homozygous for null mutations in the CaR gene (CaR(-/-)) die shortly after birth because of the effects of severe hyperparathyroidism and hypercalcemia [7].
• Effects of dietary-induced hyperparathyroidism on the parathyroid hormone-receptor-adenylate cyclase system of canine kidney. Evidence for postreceptor mechanism of desensitization [8].
• The dietary hyperparathyroidism resulted in desensitization of the PTH-responsive adenylate cyclase (Vmax 3,648 +/- 654 pmol cyclic (c)AMP/mg protein per 30 min in hyperparathyroid animals vs. 5,303 +/- 348 in normal controls) [8].
• Hyperparathyroidism is accompanied by an increase in the size of the parathyroid gland as well as an increase in PTH mRNA levels [9].

Chemical compound and disease context of Hyperparathyroidism

• In Nx rats on a MPD, serum calcitriol levels decreased only if hyperparathyroidism was not allowed to occur (76 +/- 4 vs. 62 +/- 4 pg/ml in Nx-IPTG-MPD and Nx-PTHR-MPD groups respectively, P < 0.05) [10].
• In the two other groups that also received a vitamin D-deficient diet, the hypocalcemia and the hyperparathyroidism were later corrected, by either vitamin D supplementation (D-D+) or lactose and high calcium diet (D-Ca+), 1 week before death [11].
• In summary, NA rats, which are analbuminemic with compensatory increases in lipid and protein synthesis, developed hyperparathyroidism, possibly due to an increase in serum Pi and a reduction of ionized Ca, and ovx induced a greater BMD reduction in NA rats than in SD rats, probably by exacerbating hyperparathyroidism [12].
• Ovx-induced exacerbation of hyperparathyroidism was confirmed by significantly greater conversion of 25-hydroxyvitamin D to 1, 25-dihydroxyvitamin D in ovx NA rats even after normalization to vitamin D-binding protein [12].
• This may indicate that hypertension due to nutritional hyperparathyroidism responds to the calcium antagonist nifedipine and calcium supplementation, and is not dependent on renin [13].

Biological context of Hyperparathyroidism

• The results of this study suggest that target cell resistance to PTH in patients with hyperparathyroidism might occur, at least in part, due to down-regulation of PTH receptors by circulating hormone [14].
• Endothelin receptor antagonist prevents parathyroid cell proliferation of low calcium diet-induced hyperparathyroidism in rats [15].

Anatomical context of Hyperparathyroidism

• The present study was undertaken to investigate the effect of the Hyp mutation and diet-induced hyperparathyroidism on renal responsiveness to PTH and forskolin and to determine whether the renal brush border membrane phosphate transport defect is expressed in the vitamin D- and calcium-deficient Hyp mouse [16].
• Despite aluminium administration, diet-induced hyperparathyroidism resulted in an increase (P < 0.05) in the osteoblast surface [17].
• Indeed, this action of parathyroid hormone (PTH) has only been observed in acute studies, whereas in animal models of chronic hyperparathyroidism a metabolic alkalosis has been induced, probably owing to the release of alkaline salts from bone tissue, and to the stimulation of tubular acid secretion by hypercalcaemia [18].

Gene context of Hyperparathyroidism

• To genetically separate the effects of phosphate and vitamin D on Fgf23, we examined vitamin D receptor null (VDR(-/-)) mice, which are hypocalcemic and hypophosphatemic secondary to hyperparathyroidism [19].
• Neonatal severe hyperparathyroidism (NSHPT) is considered an autosomal-recessive disorder, attributable in many cases to homozygous inactivating mutations of the Ca++-sensing receptor (CASR) gene at 3q13.3-21 [20].
• OBJECTIVE: To determine whether familial isolated hyperparathyroidism (FIHP) is a variant of multiple endocrine neoplasia type 1 (MEN1) we analyzed the MEN1 gene in such a kindred [21].
• To study the pathophysiological consequences of the deletion of the MEN1 gene, we set out to create a mouse model of hyperparathyroidism resulting from the deletion of the Men1 gene in parathyroid tissue [22].
• It encompasses a spectrum of disorders including multiple endocrine neoplasia types 1 (MEN1) and 2A, hyperparathyroidism-jaw tumour syndrome (HPT-JT), familial hypocalciuric hypercalcaemia (FHH), and familial isolated hyperparathyroidism (FIHP) [23].

Analytical, diagnostic and therapeutic context of Hyperparathyroidism

• Total Parathyroidectomy Without Autotransplantation for Renal Hyperparathyroidism: Experience with a qPTH-controlled Protocol [24].
• ELISA confirmed the pathophysiological change of a hyperparathyroidism with significantly increased serum levels of parathyroid hormone in the PKD rats [25].
• Since the role of P-gp in tertiary hyperparathyroidism (T-HPTH) scintigraphic studies is poorly recognized, the aim of the study was to compare the correlation between parathyroid P-gp expression and results of their scintigraphy in T-HPTH versus primary hyperparathyroidism (P-HPTH) [26].
• Radioimmunoassays during the experiment showed that the test animals had significantly elevated levels of parathyroid hormone, indicating a probable state of hyperparathyroidism [27].

References