超声引导下微波消融治疗继发性甲状旁腺功能亢进2例并文献复习

<正>继发性甲状旁腺功能亢进症(secondary hyperparathyroidism, SHPT)是指各种原因所致的低钙血症或高磷血症刺激甲状旁腺，使之增生肥大并分泌过多甲状旁腺激素(parathyroid hormone, PTH)而引发的综合征，     

甲状旁腺激素水平在早期肾脏损伤诊治中的意义

甲状旁腺激素(PTH)是调节人体钙磷代谢的主要激素之一。各种原因引起的长期低钙血症、高磷血症及低1,25-羟维生素D3血症可刺激甲状旁腺代偿性增生,PTH分泌增多,引发继发性甲状旁腺功能亢进(SHPT)。肾脏疾病患者肾功能下降,肾实质减少,出现钙磷代谢紊乱,引起PTH水平上升,升高     

甲状旁腺腺瘤的甲状旁腺激素分泌的反馈调节

对原发性甲状旁腺机能亢进(甲旁亢)病人甲状旁腺激素(PTH)分泌是随血钙水平调节还是自动调节一直有争论,为了研究原发性甲旁亢和PTH分泌的调节机制,作者对1例甲状旁腺腺瘤病人在术前、术后和3名健康青年进行钙和依地酸输注试验,并观     

骨质疏松及骨矿盐疾病诊疗指南(讨论稿)

甲状旁腺功能减退症 一、概述 甲状旁腺功能减退症（甲旁减）是因甲状旁腺激素（parathyroid hormone，PTH）产生减少而引起的钙、磷代谢异常。其特征是手足搐搦、癫痫发作、低钙血症和高磷血症，长期口服钙剂和维生素D制剂可使病情得到控制。     

钙敏感受体激动剂:治疗甲状旁腺功能亢进症的新药物

甲状旁腺功能亢进症（甲旁亢）与甲状旁腺激素（PTH）产生过多有关，而能够有效减低PTH分泌的药物很少。钙敏感受体可以有效调节PTH的分泌，通过对其激动剂的研究发现，Ⅱ型钙敏感受体激动剂可抑制PTH分泌，有效治疗甲旁亢。目前，盐酸西那卡赛是唯一一种美国食品与药品管理局批准上市的Ⅱ型钙敏感受体激动剂，可以使轻到中度原发性甲旁亢患者血钙恢复并保持在正常范围。     

甲状旁腺钙受体与肾性甲旁亢关系的研究进展

甲状旁腺钙受体 (CaR)是与G蛋白相偶联的膜受体。胞外Ca2 + 通过激活CaR ,可快速、独立地影响甲状旁腺激素 (PTH)的分泌。慢性肾功能衰竭 (肾衰 )继发甲状旁腺功能亢进 (甲旁亢 )时 ,Ca调定点升高 ,PTH过度分泌。多数学者认为这与甲状旁腺CaR的mRNA表达下降及受体蛋白合成减少有关 ,而与CaR的基因突变无关。CaR的激动剂能模仿甚至增强胞外Ca2 + 对甲状旁腺细胞的效应 ,初步证实它能快速、安全、有效地抑制PTH分泌 ,延缓肾性骨病的发展。     

锂刺激人的甲状旁腺激素的释放

治疗精神病的药物碳酸锂是否能促进人的甲状旁腺激素(PTH)分泌和血清钙增加尚有争论,作者用一种能测定人的完整PTH的RJA法在体外进行了研究。 材料和方法 甲状旁腺组织来源于3例甲状旁腺机能正常,3例继发于慢性肾功能衰竭的继发性甲状旁腺机能亢进,4例甲状分腺腺瘤性的原发性     

甲状旁腺腺瘤在钙浓度不同时分泌的甲旁素及其它片段

对流经牛甲状旁腺的静脉血分析表明,完整的PTH及其C一端肽段的分泌随甲状旁腺的功能而变化,因此反映了细胞内PTH的降解及PTH分泌的调节机理。为此,作者观察钙浓度不同时对免疫反应性PTH(iPTH)释放的影响以及对功能亢进的     

甲状旁腺疾病与心血管病变

甲状旁腺分泌甲状旁腺激素(PTH),调节钙磷代谢。PTH的作用有:(1)促进骨组织中钙的动员;(2)抑制近曲小管对钙,磷的再吸收,远曲小管对钙的再吸收在PTH作用下是增强的。甲状旁腺机能亢进(甲旁亢)时尿钙增加主要是肾小球滤过率增加;PTH增强肾小管1α-羟化酶的活性,从而使25-(OH)D_3     

甲状旁腺激素促进骨形成的研究进展

甲状旁腺激素（PTH）是由甲状旁腺分泌的含84个氨基酸的单链多肽蛋白质，分子置为9500U，它是调节钙、磷代谢及骨转换的最为重要的肽类激素之一。一般认为，PTH是刺激骨分解的骨代谢调节激素。其直接作用于骨和肾，     

Regulation of phosphate balance in the kidney

The reabsorption of phosphate filtered at glomeruli is mediated by sodium-dependent phosphate (Na/Pi) cotransporter families in the brush border membrane of the proximal tubuli. The type II a Na/Pi cotransporter plays the most important role for renal phosphate reabsorption and is regulated by several factors, e.g. parathyroid hormone (PTH) and fibroblastic growth factor-23. PTH induces endocytosis of the type II a Na/Pi cotransporter from the brush border membrane and subsequent lysosomal degradation, and the decrement of the type II a Na/Pi cotransporter in the brush border membrane leads the phosphate reabsorption inhibition.     

Cellular mechanisms in proximal tubular handling of phosphate

In the kidney, reabsorption of filtered inorganic phosphate (Pi) takes place along the proximal tubules and is controlled by a variety of hormones (e.g.parathyroid hormone, PTH). Three structurally unrelated sodium-dependent phosphate (Na/Pi) cotransporter families have been identified. Targeted inactivation of the type IIa Na/Pi cotransporter gene (npt2) provided strong evidence that - 70% of Na-dependent Pi transport across the brush border membrane is mediated by the type IIa Na/Pi cotransporter. The type IIa cotransporter represents the major target for PTH. The type IIa cotransporter interacts with various PDZ proteins that might be responsible for the apical sorting, PTH controlled endocytosis or the lysosomal sorting internalized type IIa cotransporter.     

Tertiary hyperparathyroidism during high phosphate therapy of familial hypophosphatemic rickets.

We report the development of severe tertiary hyperparathyroidism in three girls treated for familial hypophosphatemic rickets and characterize parathyroid function in vivo and in vitro. All patients had been previously treated with relatively large doses of inorganic phosphorus (125 mm/day) and ergocalciferol or calcitriol for several years and had radiographic evidence of long-standing hyperparathyroidism. Even in the presence of extremely elevated PTH levels, oral phosphate lowered serum calcium levels in vivo and further stimulated PTH secretion. Profound multiglandular parathyroid hyperplasia was found in each patient at surgery. Examination of the secretory characteristics of the excised parathyroid tissue revealed that either relatively high calcium concentrations were generally needed to suppress PTH secretion or PTH secretion was not suppressible. Caution is recommended when relatively large doses of phosphate are used to treat familial hypophosphatemic rickets.     

Calcium-dependent intracellular degradation of parathyroid hormone: a possible mechanism for the regulation of hormone stores.

The dynamics of parathyroid hormone (PTH) biosynthesis, storage, and secretion in bovine parathyroid slices in vitro in response to alterations in the concentrations of extracellular calcium were studied. Hormone biosynthesis was evaluated by using polyacrylamide gel electrophoresis to measure incorporation of [3H]leucine into newly synthesized PTH and proparathyroid hormone (ProPTH) during short (35 min) incubations. Amounts of newly synthesized PTH stored in and secreted from the tissue slices were determined by electrophoretic analysis of [3H]PTH in extracts of tissue and media. Total PTH and ProPTH is slices and media were measured by specific radioimmunoassays. PTH secretion rates changes 5-fold when calcium was lowered from 2mM to 1mM. Secretion of some PTH continued despite high concentrations of calcium (5 mM). Biosynthesis of ProPTH was changed only slightly, and conversion of ProPTH to PTH was independent of the extracellular calcium concentration. Tissue stores of PTH increased during incubation of parathyroid slices in medium containing high amounts of calcium. The increase in stores was much less, however, than predicted by the findings of marked suppression of secretion and little change in rates of PTH biosynthesis. In high concentrations of calcium, a large fraction (up to 50%) of newly synthesized PTH was degraded within the tissue, whereas in low concentrations of calcium, little (less than 10%) of the PTH was degraded. No fragments of PTH or ProPTH were identified in either extracts of tissue or media, suggesting that degradation occurred rapidly by general proteolysis rather than by limited, specific endopeptidase activity. The data suggest that the parathyroid cell contains a calcium-sensitive degradative pathway for PTH and that this pathway may be involved in the regulation of hormone production and secretion.     

SECRETION OF INTACT PTH BY DISPERSED HUMAN HYPERPARATHYROID CELLS

The rate of secretion of intact PTH by cells dispersed from adenomatous and hyperplastic human parathyroid tissue was measured using a two-site immunochemiluminometric assay specific for the intact peptide. Secretion rates were monitored following incubation in high and low-calcium media. The mean rate of secretion from hyperplastic cells was significantly greater (P less than 0.05) at low calcium and significantly more suppressible at high calcium (P less than 0.01) compared with adenomatous cells. These studies have demonstrated: (1) the calcium-dependent secretion of intact PTH, (2) that intact hormone release contributes to the non-suppressible component of secretion, and (3) differences in the secretory characteristics of adenomatous and hyperplastic parathyroid cells.     

Effect of somatostatin on parathyroid hormone and calcitonin secretion.

This study evaluated the effect of somatostatin on immunoreactive parathyroid hormone (iPTH) and calcitonin (iCT) secretion in vivo in rats and monkeys and on iPTH secretion in vitro by normal bovine parathyroid tissue and by a human parathyroid adenoma. Somatostatin infusion promptly (within 0.5 h) suppressed both iPTH and iCT in both species studied in vivo, the suppression being progressive during the infusion period. In in vitro studies, somatostatin caused significant dose-related decreases in basal, low Ca-stimulated, and high Ca-suppressed PTH secretion from normal bovine parathyroid tissue and from basal and low Ca-stimulated PTH secretion from a human parathyroid adenoma. Therefore, somatostatin 1) suppresses both PTH and CT secretion in vivo; 2) acts directly on the parathyroid cell and presumably directly on the C-cell also; 3) acts upon normal and adenomatous parathyroid tissue; 4) suppresses basal, low Ca-stimulated and high Ca-suppressed PTH secretion; and 5) has a dose-related effect. The possible role of somatostatin in the physiological control of PTH and CT secretion (and therefore in Ca homeostasis), and in the pathogenesis of abnormalities of Ca homeostasis, requires further evaluation.     

Plasma 25-hydroxyvitamin D and not 1,25-dihydroxyvitamin D is associated with parathyroid adenoma secretion in primary hyperparathyroidism: a cross-sectional study

BACKGROUND: Primary hyperparathyroidism (PHPT) is associated with reduced plasma 25-hydroxyvitamin D (P-25OHD) and usually increased plasma 1alpha,25-dihydroxyvitamin D (P-1,25(OH)2D). Parathyroid tissue expresses the vitamin D receptor and it is thought that circulating 1,25(OH)2D participate in the regulation of parathyroid cell proliferation, differentiation and secretion. AIM: To investigate the relations between circulating levels of 1,25(OH)2D and 25OHD respectively and parathyroid adenoma weight (AW), plasma-parathyroid hormone (P-PTH) and PTH secretion expressed as P-PTH/AW. DESIGN: Cross-sectional study. MATERIAL: One hundred and seventy-one consecutive hypercalcaemic caucasian patients aged 19-87 years (median 63, 84% females) with surgically proven parathyroid adenoma. RESULTS: A weak positive correlation was found between P-25OHD and P-1,25(OH)2D (r=0.24, P<0.005). AW depended on sex and body mass index. Following adjustment, it was correlated positively to P-PTH, calcium (Ca) and alkaline phosphatase (AP) and inversely to plasma phosphate in a multiple regression model. AW was not associated with vitamin D metabolites. Preoperative P-PTH correlated positively to plasma levels of Ca and AP, but inversely to phosphate and 25OHD (P<0.001) levels. P-PTH was not associated with P-1,25(OH)2D (P=0.65). The P-PTH:AW ratio correlated inversely to P-25OHD (P<0.05), but showed no relations to plasma levels of Ca, phosphate or 1,25(OH)2D (P=0.22). CONCLUSION: In this material, low levels of 25OHD were related to higher levels of P-PTH and higher PTH:AW ratios in patients with PHPT suggesting that vitamin D deficiency increase PTH secretion activity. Neither PTH secretion nor AW was associated with circulating levels of 1,25(OH)2D.     

The calcium channel blocker diltiazem lowers serum parathyroid hormone levels in vivo and in vitro

PTH secretion is inversely related to the extracellular and cytosolic calcium (Ca2+) concentrations and, therefore, might be affected by calcium channel blockers such as diltiazem. To investigate the effects of diltiazem on parathyroid function in vivo, 15 subjects were treated with diltiazem (120-360 mg/day), and 15 subjects were treated with the nonspecific vasodilator hydralazine (75-150 mg/day). Diltiazem lowered serum PTH levels from 1.07 +/- 0.07 to 0.87 +/- 0.07 pg/L (P = 0.001), and increased urinary calcium and decreased urinary phosphate excretion (P less than 0.001 and P less than 0.01, respectively). The hydralazine-treated subjects had no significant differences in any of these parameters. To investigate this effect further, dispersed bovine parathyroid cells were incubated for 2 h with or without diltiazem. Regression analysis of PTH released vs. the concentration of diltiazem (10(-7)-10(-4) mol/L) revealed a significant negative relationship (P less than 0.01) with 40% inhibition of PTH release at 10(-4) mol/L (P less than 0.01). The cytosolic Ca2+ concentration, measured using the Ca2+-sensitive fluorescent dye fura-2, was significantly increased in the presence of 10(-4) mol/L diltiazem (P less than 0.01). In summary, diltiazem lowered PTH levels in vivo and in vitro, perhaps acting as a Ca2+ channel agonist in the parathyroid cell and inhibiting PTH release through a rise in the cytosolic Ca2+ concentration.     

Role of endogenous somatostatin in the secretion of parathyroid hormone and calcitonin.

Our previous in vitro and in vivo studies demonstrated that exogenous somatostatin inhibited secretion of both parathyroid hormone (PTH) and calcitonin (CT). This study evaluates the possible role of endogenous somatostatin in PTH and CT secretion. Rats receiving somatostatin antiserum i.v. had significantly greater circulating levels of serum immunoreactive PTH (iPTH) and CT (iCT) than rats receiving normal rabbit serum. In in vitro studies with bovine parathyroid tissue, the addition of somatostatin antiserum to the medium significantly increased PTH secretion from basal, low calcium-stimulated and high calcium-suppressed parathyroid tissue. These combined observations strongly suggest that endogenous somatostatin must have a suppressive effect on PTH and CT secretion. The in vitro observations with isolated parathyroid tissue suggest that somatostatin is synthesized by cells within this tissue. These data strongly suggest that somatostatin is a locally-synthesized hormone that has a role in modulation of both PTH and CT secretion.     

Role of the sodium-dependent phosphate cotransporter, Pit-1, in vascular smooth muscle cell calcification

Vascular calcification is associated with cardiovascular morbidity and mortality. Hyperphosphatemia is an important contributor to vascular calcification. Our previous studies demonstrated that elevated phosphate induces calcification of smooth muscle cells (SMC) in vitro. Inhibition of phosphate transport by phosphonoformic acid blocked phosphate-induced calcification, implicating sodium-dependent phosphate cotransporters in this process. In the present study, we have investigated the role of the type III sodium-dependent phosphate cotransporter, Pit-1, in SMC calcification in vitro. Human SMC stably expressing Pit-1 small interfering double-stranded RNA (SMC-iRNA) were established using a retroviral system. SMC-iRNA had decreased Pit-1 mRNA and protein levels and sodium-dependent phosphate transport activity compared with the control transduced cells (SMC-CT) (2.9 versus 9.78 nmol/mg protein per 30 minutes, respectively). Furthermore, phosphate-induced SMC calcification was significantly inhibited in SMC-iRNA compared with SMC-CT at all time points examined. Overexpression of Pit-1 restored phosphate uptake and phosphate-induced calcification in Pit-1 deficient cells. Mechanistically, although Pit-1-mediated SMC calcification was not associated with apoptosis or cell-derived vesicles, inhibition of phosphate uptake in Pit-1 knockdown cells blocked the induction of the osteogenic markers Cbfa-1 and osteopontin. Our results indicate that phosphate uptake through Pit-1 is essential for SMC calcification and phenotypic modulation in response to elevated phosphate.