继发性甲状旁腺功能亢进症的治疗进展

CKD早期就会出现钙、磷、维生素D和PTH代谢失衡,并引起继发性甲状旁腺功能亢进症(SHPT),随着肾功能下降,SHPT也愈加明显。SHPT的治疗相当棘手,标准的治疗方法包括补钙、限制磷摄入、磷结合剂及维生素D制剂的应用。但这些治疗通常会影响血钙、磷浓度,从而加重疾病并增加骨骼外并发症的发病率和死亡率。本文就SHPT的治疗方面作一综述。     

外科手术在继发性甲状旁腺功能亢进症中的地位

<正>近年来,慢性肾脏病(chronic kidney disease, CKD)已成为影响我国公共卫生健康的重大问题之一。目前,我国CKD的患病率约为10.8%(11.7%～15.1%)[1-2]。继发性甲状旁腺功能亢进(secondary hyperparathyroidism, SHPT)是CKD 最常见的并发症之一,SHPT病人钙磷代谢紊乱刺激甲状旁腺过度分泌甲状旁腺激素(parathyroid hormone, PTH),     

继发性甲状旁腺功能亢进症外科治疗现状

继发性甲状旁腺功能亢进症(SHPT)是终末期慢性肾脏病(CKD)最为常见的并发症,通常表现为骨关节疼痛、骨骼畸形、四肢麻木乏力等一系列症状,严重影响患者的生存质量。有效的治疗干预对降低SHPT患者的病死率和发病率是非常重要的。多数早期患者应用药物结合充分透析的方式进行控制是非常有效的,但随着病情的进展,SHPT会进入不...     

尿毒症伴重度继发性甲状旁腺功能亢进症骨密度特征 分析

目的研究尿毒症伴重度继发性甲状旁腺功能亢进症患者的骨密度改变特征,分析该组患者骨密度改变与临床特征之间的关系。方法回顾性总结2011年2月至2013年4月在本院接受甲状旁腺全切除联合自体前臂移植术的51例尿毒症伴重度继发性甲状旁腺功能亢进症患者的一般情况、临床特点、股骨近端和腰椎骨密度,及全切除手术所得甲状旁腺质量等数据。比较相同性别患者腰椎L1-L4之间、股骨近端不同部位之间骨密度的差异;对不同部位骨密度减少程度与上述观察变量之间的关系进行相关性分析。结果本组患者临床表现包括皮肤瘙痒、骨痛、身高缩短、面部变形和躯体变形等;血清iPTH高达2227.9±907.3 pg/ml;骨质疏松27例(52.9%),骨量减少23例(45.1%);男女性患者均显示L1至L4椎骨骨密度T值逐渐降低,男性骨密度T值L4显著低于L1(P=0.037),女性骨密度T值L4亦显著低于L1(P=0.039),男女性均显示股骨转子、股骨颈至Ward’s三角区的T值逐渐降低,男性Ward’s三角区T值显著低于股骨转子(P=0.025),女性Ward’s三角区和股骨颈T值显著低于股骨转子(P=0.009和P=0.023)。体重指数、血清白蛋白与骨密度值呈显著正相关,身高缩短、脊柱变形、胸廓变形、面部变形、血清碱性磷酸酶、血清iPTH、甲状旁腺质量与骨密度值呈显著负相关。结论骨质疏松和骨量减少广泛存在于尿毒症伴重度继发性甲状旁腺功能亢进症患者中;身体承重部位骨密度降低更严重;消瘦、低白蛋白血症、面部及躯干变形、iPTH严重升高、甲状旁腺增生程度重等因素提示骨质疏松风险增大。     

继发性甲状旁腺功能亢进症非药物治疗的研究进展

[摘要] 继发性甲状旁腺功能亢进症是慢性肾脏病患者常见的严重并发症,临床表现多样,多系统受累,预后不良。随着临床研究探索不但深入,近年来临床治疗方法逐渐增多,特别是非药物治疗研究发展较快,且临床效果明确,本文对继发性甲状旁腺功能亢进症的非药物治疗进展情况进行综述。     

近红外自体荧光显影技术在继发性甲状旁腺功能亢进症患者甲状旁腺切除术中的应用

分析近红外自体荧光显影技术在继发性甲状旁腺功能亢进症患者手术中辨认甲状旁腺的确切性及实用性。报告1例继发性甲状旁腺功能亢进患者,术中甲状旁腺显露后进行甲状旁腺自体荧光显像,并在4枚甲状旁腺切除后对术区进行甲状旁腺自体荧光显像搜寻有无遗漏甲状旁腺,标本离体后再次行甲状旁腺自体荧光显像了解该系统是否受血流灌注影响,最后所有标本切除后送冰冻病检进行确认。结果显示,术中使用近红外自体荧光显影技术探测到有明显自体荧光的4枚甲状旁腺后经病理证实确为增生的甲状旁腺组织,另1枚荧光强度相对偏低的可疑甲状旁腺组织病理回报为甲状腺组织,术后即时检测甲状旁腺激素明显降低。结果表明,在体甲状旁腺在近红外光谱中呈现较强的自体荧光特征,该特征可用于术中与周围甲状腺及脂肪组织的肉眼识别,从而协助临床医师在术中快速的辨认继发性甲状旁腺功能亢进症患者的增生甲状旁腺组织。     

继发性甲状旁腺功能亢进症的外科治疗

继发性甲状旁腺功能亢进症(SHPT)是由于各种原因引起机体低血钙或高血磷,长期刺激甲状旁腺分泌过量的甲状旁腺素而导致的一种临床综合征。当药物及一般治疗效果不佳时就进展成为难治性SHPT,此时通过手术或局部介入性治疗可获得良好疗效。笔者从手术治疗和局部介入治疗方面探讨外科治疗SHPT疗效,并讨论分析这些治疗方法的前景。     

成纤维细胞生长因子23在继发性甲状旁腺功能亢进症中的作用

目的 研究成纤维细胞生长因子23（FGF23）在继发性甲状旁腺功能亢进症（SHPT）中的作用。 方法 （1）收集38例维持性血液透析（MHD）患者血清,用ELISA法检测FGF23和化学发光酶免疫分析法检测全段甲状旁腺激素（iPTH）。（2）6例行甲状旁腺全切除（PTX）加自体前臂移植术的SHPT患者,取其甲状旁腺组织行细胞培养。培养24 h后用0.1 mg/L的FGF23分别刺激0、6、12、24、48 h时收集上清液检测iPTH。（3）取33例严重SHPT患者和3例健康人的甲状旁腺组织,用免疫组化SP法检测成纤维细胞生长因子受体（FGFR）1、FGFR3、转录因子GATA-3、增殖细胞核抗原（PCNA）及PV法检测Klotho的表达,计算阳性细胞率或积分吸光度。 结果 (1)MHD患者血清FGF23[（3901.85±2618.11） ng/L]与iPTH[（460.00±489.77） ng/L]呈正相关（r2 = 0.3009,P = 0.0004）。(2)FGF23仅在刺激24 h时,才有抑制iPTH的作用（P ＜ 0.05）,其它时段均无抑制作用。(3)SHPT患者甲状旁腺PCNA、 GATA-3、 FGFR3、 Klotho表达均显著高于健康人,而FGFR1表达显著低于健康人。(4)GATA-3阳性细胞率与血清iPTH水平及PCNA阳性细胞率均呈正相关（r2 = 0.1901,P = 0.0425;r2 = 0.2584,P = 0.0025）。Klotho表达与FGFR1和FGFR3表达呈正相关（r2 = 0.2046,P = 0.0082;r2 = 0.2833,P = 0.0014）。PCNA表达与FGFR1表达呈负相关（r2 = 0.1292,P = 0.0399);与FGFR3表达呈正相关（r2 = 0.1226,P = 0.0457）。FGFR1表达和血清磷水平呈负相关（r2 = 0.2329,P =0.0044）;与血清钙水平呈正相关（r2 = 0.1422,P = 0.0305）。 结论 MHD患者iPTH水平与FGF23水平呈正相关。FGF23能抑制iPTH分泌,但作用弱且短。这可能与GATA-3、甲状旁腺细胞增殖、FGFR3表达增多,FGRF1表达下降有关。     

Efficacy of microwave ablation for severe secondary hyperparathyroidism in subjects undergoing hemodialysis

Severe secondary hyperparathyroidism (SHPT) is a serious problem in patients undergoing hemodialysis. The efficacy and safety of microwave ablation (MWA), a minimally invasive treatment, for severe SHPT are as yet unclear. To clarify the role of MWA, we administered it to patients with severe SHPT and assessed its efficacy and safety. This was a prospective, single-center, single-arm, clinical trial. We enrolled patients with severe SHPT attending our hemodialysis center who met the inclusion and exclusion criteria. We then assessed primary outcome measures (serum concentrations of intact parathyroid hormone) and secondary outcome measures (serum concentrations of calcium and phosphorus). Twenty-six patients were enrolled in this study, 10 of whom (38.46%) were responsive to MWA and 16 (61.54%) of whom were not. The main complication was hypocalcemia (10 cases, 38.46%), which had occurred in all cases by one week after administration of MWA. Responding patients with hypocalcemia all achieved normal serum calcium concentrations within seven months and non-responding patients within three months. There were no changes in serum phosphorus concentrations after MWA in either responders or non-responders. Microwave ablation is relatively ineffective in patients with severe SHPT undergoing maintaining hemodialysis and should not be the initial therapy in such cases.     

微波消融治疗不宜手术切除继发性甲状旁腺功能亢进临床效果

目的观察微波消融(MWA)治疗不宜手术切除继发性甲状旁腺功能亢进症(SHPT)患者的有效性及安全性。方法回顾性分析51例接受MWA治疗的SHPT患者,对比消融前后单个增生结节最大径及血清全段甲状旁腺素(iPTH)、钙和磷水平,统计随访期间并发症、局部复发率及新发率。结果51例SHPT共83枚甲状旁腺增生结节均一次性完全消融。消融后3、6个月及随访结束时,单个增生结节最大径均较消融前缩小(P均<0.05),血清iPTH、钙、磷水平均低于消融前(P<0.05)。随访期间9例(9/51,17.65%)发生与MWA相关的轻微并发症,无严重并发症。随访结束时,局部复发率为5.88%(3/51),新发率7.84%(4/51)。结论MWA用于治疗不宜手术切除SHPT安全有效。     

超声引导下微波消融治疗异位继发性甲状旁腺功能亢进症

目的观察超声引导下微波消融(MWA)治疗异位继发性甲状旁腺功能亢进症(SHPT)的安全性及有效性。方法对36例异位SHPT患者行超声引导下MWA治疗。术后定期随访,观察症状改善情况,记录不良反应。检测术前、术后第1天及末次随访时血清全段甲状旁腺激素(iPTH)、钙、磷及碱性磷酸酶(ALP)水平。结果 36例共40枚异位SHPT结节均完全消融。术后第1天血清iPTH、钙、磷均低于术前(P均0.05);末次随访时iPTH、磷、ALP均较术前降低(P均0.01)。术中4例出现短暂轻至中度疼痛,均自行缓解;1例发生血肿,经静脉注射血凝素后出血得到控制。术后1～3天10例出现低钙血症,经补钙治疗后8例血钙恢复正常,2例至随访结束时仍为轻度低钙血症;2例术后声音嘶哑,1～3个月内恢复;1例出现轻度霍纳综合征,未予特殊处理,随访期间症状逐渐改善后消失。结论超声引导下MWA治疗异位SHPT结节安全、有效。     

帕立骨化醇治疗维持性血液透析患者继发性甲状旁腺功能亢进症的前瞻性研究

目的 观察帕立骨化醇治疗维持性血液透析患者继发性甲状旁腺功能亢进症（secondary hyperparathyroidism,SHPT）的疗效及安全性.方法 选择我科血液净化中心进行维持性血液透析治疗的13例患者,血全段甲状旁腺素（intact parathyroid hormone,iPTH）≥33 pmol/L,血钙水平＜2.55 mmol/L,钙磷乘积＜65,根据iPTH水平使用帕立骨化醇1～18 μg治疗,于每次透析治疗后给药,共观察12周.分别于治疗前及治疗后第2、4、6、8、10、12周测定患者的iPTH、血钙、血磷水平.结果 13例患者的血清iPTH水平在治疗后第2、4周已开始下降,但与治疗前相比差异无统计学意义.从治疗后第6周开始,iPTH水平与治疗前相比存在统计学差异（P＜0.05）,治疗后第12周时下降至（46.68±38.06） pmol/L,与治疗前（78.30±52.13） pmol/L比较,有统计学差异（P＜0.01）.治疗后第2、4周血钙水平升高,与治疗前比较有统计学差异（P＜0.05）,其中治疗后第4周时血钙水平升高尤为显著（P＜0.01）.经调整帕立骨化醇剂量后,治疗后第6周患者的血钙水平逐渐恢复正常并保持稳定,血磷、钙磷乘积水平在治疗前、后均无明显统计学差异.治疗过程中,患者耐受性良好,无相关不良反应的发生.结论 使用帕立骨化醇治疗维持性血液透析患者SHPT是有效、安全的.     

Impact of parathyroidectomy among nondiabetic hemodialysis patients with severe hyperparathyroidism

BackgroundParathyroidectomy (PTX) is a treatment for hyperparathyroidism (HPT) and has uncertain risks and benefits. The aim of this study was to evaluate the effect of PTX versus nonoperative treatment among nondiabetic hemodialysis patients.MethodsA retrospective matched cohort study was performed. Each PTX patient was matched with one patient who had severe HPT but rejected PTX. The patients were matched by sex, birth date, date of first dialysis, nondiabetic status, and left ventricular ejection fraction. The serum markers, survival, main adverse cardiovascular and cerebrovascular event (MACCE) rates, and hospitalization were compared between the PTX patients and matched non-PTX patients.ResultsThere were 1143 patients at our center in the Chinese National Renal Data System (CNRDS) between 2010 and 2020. Of these, 75 PTX patients were matched with 75 non-PTX patients. Rapid decreases in the mean intact parathyroid hormone, calcium and phosphorus concentrations, and a gradual increase in hemoglobin concentration were observed in the PTX group. The mortality was 2.9 per 100 patient-years in the PTX group and 10.9 per 100 patient-years in the non-PTX group (p < 0.001). Compared with non-PTX patients, PTX patients had an adjusted HR for death of 0.236 (95% CI 0.108–0.518). The cumulative MACCE rates were 6.7 per 100 patient-years in the PTX group and 15.2 per 100 patient-years in the non-PTX group (p < 0.001). The adjusted HR of the occurrence of first MACCE for PTX patients compared with non-PTX patients was 0.524 (95% CI 0.279-0.982). The cumulative hospitalization rates were 50.3 per 100 patient-years in the PTX group and 66.5 per 100 patient-years in the matched non-PTX group (p < 0.001).ConclusionsCompared with non-PTX patients, PTX was associated with an improvement in the biochemical measures and patient-level outcomes in nondiabetic hemodialysis patients with severe HPT.     

超声造影评估继发性甲状旁腺功能亢进症结节功能

目的分析超声造影(CEUS)评估继发性甲状旁腺功能亢进症(SHPT)结节功能的价值。方法回顾性分析16例SHPT(16枚结节),观察其CEUS特点;获取结节长宽乘积、总亮度计数(TBC)及时间-强度曲线(TIC)相关参数,包括绝对峰值强度(API)、相对峰值强度(RPI)、达峰时间(TTP)及上升支斜率(BPAS)等,分析其与全段甲状旁腺激素(iPTH)及钙、磷、碱性磷酸酶水平的相关性。结果二维超声声像图显示SHPT结节边界清晰,呈圆形或椭圆形,其中9枚为低回声-无回声囊实性结节,6枚为实性低回声结节,1枚呈等-低混合回声。CEUS示9枚呈高增强,相应患者血清iPTH为1 639.80(1 328.80,2 144.80)pg/ml; 7枚呈低增强,患者血清iPTH为974.20(211.00,1 221.80)pg/ml,差异有统计学意义(U=53.000,P=0.023)。Pearson相关分析结果显示,iPTH与BPAS(r~2=0.341,P=0.003)、RPI(r~2=0.465,P=0.002)及TBC(r~2=0.485,P=0.002)均呈正相关,与TTP呈负相关(r~2=0.790,P=0.001),与结节长宽乘积(r~2=0.029,P=0.248)及API(r~2=0.065,P=0.175)无明显相关性;CUES参数与钙、磷、碱性磷酸酶水平均无明显相关性(P均0.05)。结论 CEUS可用于初步预测SHPT结节的分泌功能。     

超声引导下微波消融治疗肾移植术后继发性甲状旁腺功能亢进

目的评估超声引导下微波消融(MWA)治疗肾移植术后继发性甲状旁腺功能亢进(SHPT)的安全性和有效性。方法回顾性分析20例肾移植术后接受MWA治疗的SHPT患者,比较消融前后全段甲状旁腺激素(iPTH)、血钙、血磷、血肌酐和血尿素氮水平变化。结果20例患者共34枚甲状旁腺增生结节均一次性完全消融,平均最大径为(1.41±0.61)cm,中位消融时间219 s。消融后iPTH、血钙、血磷水平均明显低于消融前(P<0.05)。血肌酐、血尿素氮水平在消融前后无明显变化(P>0.05)。未见手术相关严重并发症发生。结论超声引导下MWA是治疗肾移植后SHPT安全、有效的方法。     

Coexistence of thyroid carcinoma and secondary hyperparathyroidism

Summary Background Reports on the coexistence of secondary hyperparathyroidism (sHPT) and thyroid carcinoma are very rare. Methods A case of secondary hyperparathyroidism and concomitant papillary thyroid carcinoma (follicular variant) is described, and compared to data from the literature. Results 1 out of 26 patients undergoing parathyroidectomy for secondary hyperparathyroidism had papillary thyroid microcarcinoma (follicular variant) associated with regional lymph node metastases. Head and neck were not irradiated during the patient’s case history. Dialysis had been performed for 23 years prior to simultaneous near-total thyroidectomy, total parathyroidectomy and autotransplantation. The prolonged high parathyroid hormone levels, or massive hemosiderin deposits may have caused the development of carcinoma. The incidence rate of occult thyroid microcarcinoma in all autopsies of our geographical region and period was 4.5 per cent. Conclusions Careful exploration of the thyroid gland, and liberal indication for biopsy of suspicious thyroid areas is mandatory in each sHPT patient who is operated on, in order to exclude possible thyroid carcinomas.      

Gallstones were associated with the gastrointestinal adverse events of cinacalcet in hemodialysis patients with secondary hyperparathyroidism

This study aimed to investigate the association of gastrointestinal (GI) adverse events of cinacalcet with gallstones in the hemodialysis (HD) patients with secondary hyperparathyroidism (SHPT). A total of 23?HD patients under the treatment with cinacalcet and 101 control patients were enrolled in this cross-sectional study. We investigated the prevalence of gallstones and the association of GI adverse events of cinacalcet with gallstones. The prevalence of gallstones was significantly higher in the HD patients with cinacalcet compared with the controls (47.8% vs. 15.8%). The longer time on HD, hypercalcemia, hyperphosphatemia and elevated parathyroid hormone level were observed in the HD patients with cinacalcet. Besides, GI adverse events of cinacalcet were observed more frequently in the HD patients with gallstones compared with those without gallstones (odds ratio 13.5, 95% CI: 1.80–101). Therefore, screening for gallstones before dosing cinacalcet may reduce the risk of GI adverse events in SHPT patients.