Decreased renal transplant function after parathyroidectomy.

BACKGROUND: Persistent secondary hyperparathyroidism after renal transplantation may require parathyroidectomy (PTX). Clinical experience suggests that these patients commonly develop decreased renal function thereafter. METHODS: To test this notion, we evaluated 76 transplant patients who underwent pararhyroidectomy between 1997 and 2003. RESULTS: In half the patients (47%), creatinine clearance decreased >20% (before vs after PTX, 57 +/- 21 vs 38 +/- 17 ml/min, P = 0.001). The patients with decreased creatinine clearance had higher parathyroid hormone (PTH) concentrations before and lower values after PTX compared with those who did not (594 +/- 392 vs 447 +/- 234 pg/ml before PTX, P = 0.03; 35 vs 123 pg/ml thereafter, P = 0.002). They also had lower serum calcium concentrations after PTX (2.0 vs 2.2 mmol/l, P = 0.005) and they required more calcium and vitamin D analogues. These patients also more commonly underwent total PTX with autotransplantation, compared with subtotal (75 vs 50%, P = 0.03). However, in multivariate analysis, only the delta PTH decline (%) after PTX was a significant predictor of deteriorating renal function (P = 0.005) and was correlated with the creatinine clearance decrease (R = 0.369, P = 0.001). Prospectively measured inulin and para-amino-hippuric acid (PAH) clearance decreased significantly after PTX in a subgroup of 19 patients (inulin before vs after PTX 67 vs 55 ml/min/1.73 m(2), P = 0.001; PAH 360 vs 289 ml/min/1.73 m(2), P = 0.001). Transplant biopsies revealed calcification in 70% of biopsied cases. CONCLUSION: Since PTH has a known positive regulatory effect on renal perfusion and glomerular filtration rate, we conclude that relative hypoparathyroidism after PTX is the main mechanism contributing to decreased renal function in these patients. There was no difference in 10-year-graft survival between the deteriorating and the non-deteriorating group.     

Total parathyroidectomy with autotransplantation in renal hyperparathyroidism: low recurrence after intra-operative tissue selection.

BACKGROUND: Total parathyroidectomy with simultaneous autotransplantation (AT) is a well-established surgical modality in the treatment of severe drug-resistant renal hyperparathyroidism. In literature, the high rate of graft-dependent recurrence seems a serious disadvantage. This complication can possibly be avoided by parathyroid tissue selection prior to AT. METHODS: Total parathyroidectomy with simultaneous AT was performed in 37 patients on intermittent haemodialysis treatment. Parathyroid tissue with a low proliferative potential ('A-regions') was selected for AT intra-operatively with a stereomagnifier. The mean post-operative follow-up was 37+/-24 months. RESULTS: Plasma levels of intact parathyroid hormone decreased from 1211+/-541 to 69+/-32 pg/ml, calcium from 2.49+/-0.27 to 2.17+/-0.30 mmol/l, phosphorus from 2.28+/-0.63 to 2.11+/-0.69 mmol/l, and total alkaline phosphatases from 272+/-210 to 117+/-70 U/l. Graft-dependent recurrent hyperparathyroidism occurred in one patient after 32 months and was cured by the selective removal of five enlarged autografts. CONCLUSIONS: Simply discriminating between diffuse and nodular hyperplastic parathyroid tissue appears to be inadequate. Intra-operative tissue selection with a stereomagnifier may facilitate the identification and AT of tissue with optimal functional characteristics and a low proliferative potential, thus minimizing the rate of recurrent hyperparathyroidism.     

继发性甲状旁腺功能亢进患者术后临床评估

目的探讨继发性甲状旁腺功能亢进患者行甲状旁腺全切除或次全切除术后的预后。方法选择2009年1月至2012年12月在深圳市人民医院行慢性肾替代治疗合并继发性甲状旁腺功能亢进症手术治疗后的88例患者进行1~4年随访观察。术中留取血液样本送检测全段甲状旁腺素(immunoreactive parathyroid hormone,iPTH)水平(电化学发光法),根据测定的iPTH水平,由外科医生决定手术方式为次全切除或全切除术。根据手术方法将88例患者分为次全切除组和全切除组。次全切除组64例,男35例,女29例;全切除组24例,男女各12例;比较2组患者术后的复发率及预后。另外根据术后随访及血清iPTH的检测,将88例患者复发分为复发组和未复发组。复发组11例,男6例,女5例;未复发组77例,男41例,女36例;应用Log-rank检验对复发情况进行分析,并对可能影响复发的因素进行分析。结果 88例患者进行了(21±11.3)个月的随访研究,复发患者术后第2天iPTH水平(111.20±81.4)ng/L高于未复发患者iPTH(24.4±35.8)ng/L,2组比较有统计学差异(t=-3.486,P0.01);随访期间次全切除组10人复发,全切除组1人复发,经Log-rank检验不同手术组的未复发率无统计学差异(χ~2=0.33,P=0.57)。全部88例患者术后第12、26、36个月累积未复发率分别为98.8%、91.3%及67.1%。结论维持性透析继发性甲状旁腺功能亢进患者行甲状旁腺全切除或次全切除术后的1~4年内复发率无显著差异,术后患者症状明显改善,术后第二天的iPTH水平可能与复发相关。     

Minimally invasive video-assisted subtotal parathyroidectomy with thymectomy for secondary hyperparathyroidism

Background  Secondary hyperparathyroidism (sHPT) is common in patients with chronic renal failure. Bilateral cervical exploration is optimal for patients with sHPT. The aims of this clinical trial are to evaluate the feasibility of video-assisted subtotal parathyroidectomy as an alternative surgical treatment for sHPT. Methods  This prospective study included 12 consecutive patients with sHPT. Surgical indications included a high intact parathormone level, enlarged parathyroid glands, high bone turnover and conditions refractory to medical treatment of hypercalcemia and hyperphosphatemia. Results  All patients underwent minimally invasive video-assisted subtotal parathyroidectomy and trans-cervical thymectomy. Four cervical glands were found in all patients and intrathymic glands were identified in three (25%) patients. Conclusion  Minimally invasive video-assisted subtotal parathyroidectomy offers an alternative method, and this technique can be performed safely for sHPT.     

Total parathyroidectomy versus total parathyroidectomy with autotransplantation for secondary hyperparathyroidism: systematic review and meta-analysis

Background: Total parathyroidectomy (tPTX) and total parathyroidectomy with autotransplantation (tPTX?+?AT) are effective and inexpensive treatments for secondary hyperparathyroidism (sHPT), but we do not know which one is the optimal approach. Therefore, we undertook a meta-analysis to compare the safety and efficacy of these two surgical procedures.

Methodology: Studies published in English on PubMed, Embase and the Cochrane Library from inception to 27 September 2016 were searched systematically. Eligible studies comparing tPTX with tPTX?+?AT for sHPT were included and Review Manager v5.3 was used.

Results: Eleven studies were included in this meta-analysis. Ten cohort studies and one randomized controlled trial (RCT) involving 1108 patients with sHPT were identified. There was no significant difference in the prevalence of surgical complications (relative risk [RR], 1.71; 95% confidence interval [CI], 0.77–3.79; p?=?.19), all-cause mortality (RR, 0.68; 95% CI, 0.33–1.39; p?=?.29), sHPT persistence (RR, 3.81; 95% CI, 0.56–25.95; p?=?.17) or symptomatic improvement (RR, 1.02; 95% CI, 0.91–1.13; p?=?.79). tPTX could reduce the risk of sHPT recurrence (RR, 0.19; 95% CI, 0.09–0.41; p?p?=?.01) compared with tPTX?+?AT. Simultaneously, tPTX increased the risk of hypoparathyroidism (RR, 2.63; 95% CI, 1.06–6.51; p?=?.04).

Conclusions: We found tPTX and tPTX?+?AT to be useful methods for sHPT treatment. tPTX was superior for reducing the risk of sHPT recurrence and reoperation than tPTX?+?AT but, due to a lack of high statistical-power RCTs, comparative studies will be needed in the future.     

Identification of risk factors for radiographic hyperparathyroidism in 422 patients with end-stage renal disease: development of a clinical predictive index.

The hand radiographs of 422 patients with end-stage renal failure were graded for severity of subperiosteal resorption. Two hundred and seventy-three patients (64.7%) had no evidence of resorption; 114 (27.0%) showed resorption, in 32 of whom it was severe (7.6% of the total). Thirty-five patients (8.3%) were assessed as having doubtful evidence of subperiosteal resorption. Age, gender, race, renal diagnosis, duration of renal failure and vitamin D status were assessed as potential risk factors for the development of subperiosteal resorption. Duration of renal failure, female gender, young age, and certain renal diagnostic groups namely obstructive uropathy, unknown diagnosis, presumed glomerulonephritis and tubulointerstitial disease emerged as independent risk factors. Diabetic patients appeared to be least at risk of developing subperiosteal resorption. Patients whose renal failure was of unknown duration showed a degree of risk similar to those whose duration was < 2 years. In order to identify prospectively patients likely to develop subperiosteal resorption by the time they reach renal replacement therapy, the relative risks were used to create a risk index. Use of such an index might allow prophylactic treatment to be given to those particularly at risk. The concept of a risk index requires testing by a prospective study, which is in progress.     

Secondary hyperparathyroidism: Pathophysiology, histopathology, and medical and surgical management

It is generally accepted that morphological changes of the parathyroid glands appear early in renal failure. When diffuse hyperplasia develops into a nodular type, the cells grow monoclonally and proliferate aggressively, with abnormal suppression of parathyroid hormone (PTH) secretion under high extracellular calcium. Based on histopathological and pathophysiological findings, patients with nodular hyperplasia in renal hyperparathyroidism might be refractory to medical treatment, including calcitriol pulse therapy. Thus, parathyroid surgery is indicated for individuals developing hypercalcemia, elevated PTH levels, and/or bone disease, who cannot be effectively treated medically. The detection of enlarged parathyroid glands by image diagnosis is another criterion for surgery. In our experience, parathyroidectomy is an effective treatment; however, the timing of the operation is important, because skeletal deformity and vessel calcification cannot be expected to diminish even after successful surgery. Technically, it is important to identify all parathyroid glands and, in autotransplantation, to use an adequate amount of suitable, tissue, namely, a diffuse type of hyperplastic tissue, to guarantee satisfactory postoperative function.     

原发性甲状旁腺功能亢进术后低钙血症相关因素分析

目的 探讨原发性甲状旁腺功能亢进术后出现低钙血症及其症状的相关因素。方法 收集2009年1月至2015年3月北京协和医院行手术治疗的原发性甲状旁腺功能亢进病人临床资料,分析与术后低钙血症及其症状相关的临床因素。 结果 641例原发性甲状旁腺功能亢进病人成功接受甲状旁腺切除术治疗,并得到术后病理学诊断及长期随访证实。118例（18.4%）术后第一日血清总钙低于正常值下限,210例（32.8%）出现低钙血症相关的临床症状。多因素相关分析发现：原发性甲状旁腺病人术后出现低钙血症相关症状,与病人年龄、术前血清无机磷及碱性磷酸酶（ALP）相关;术后第一日血清总钙水平低于正常与术前血清全片段甲状旁腺激素（iPTH）水平相关。 结论 青年病人、术前血清iPTH和ALP水平增高、血清无机磷水平低可能是原发性甲状旁腺功能亢进术后低钙的相关因素。     

Focused versus conventional parathyroidectomy for primary hyperparathyroidism: a prospective,randomized, blinded trial

BACKGROUND: For many years bilateral neck exploration (BNE) was the gold standard operation for primary hyperparathyroidism (pPHP). With advances in preoperative pathological gland localization and intraoperative parathyroid hormone (IPTH) monitoring, minimally invasive approaches have evolved. This study is aimed to compare BNE and focused parathyroidectomy (FP) in a prospective, randomized, blind trial. PATIENTS AND METHODS: Between 2005 and 2007, 48 patients with pPHP were enrolled in our study. Twenty three patients were randomized to the BNE group and 24 to the FP group. Patients in the FP group underwent preoperative localization studies. All parathyroidectomies were guided by intraoperative intact parathyroid hormone (IIPTH) monitoring. In the BNE group, neither IIPTH nor preoperative localization studies were performed. RESULTS: All patients were cured by the primary operation. Overall, the operative time was similar in both groups. In the focused exploration (FE) group, compared to the BNE group, there was lower pain intensity at 4, 8, 16, 24, 36 and 48 h after surgery (p < 0.001), lower consumption of analgesics (p < 0.001), lower analgesia request rate (p < 0.001), shorter scar length (p < 0.001), higher cosmetic satisfaction rate 2 days, 1 month (p < 0.001) and 6 months after surgery (p < 0.05), but after 1 year cosmetic satisfaction rate became not significant (p = 0.38). Focused exploration (FE) was more expensive (p < 0.05). We did not find any difference in quality of life after 1 month and 6 months after surgery in both groups. CONCLUSION: Both methods of parathyroidectomy for PHP are safe and effective. Focused exploration (FE) has several advantages: lower postoperative pain, lower analgesic request rate, lower analgesic consumption, shorter scar length, better cosmetic satisfaction rate in a short time period.     

Factors related to the recurrent hyperfunction of autografts after total parathyroidectomy in patients with severe secondary hyperparathyroidism

Total parathyroidectomy with autotransplantation has been widely accepted as the appropriate treatment for patients with hyperparathyroidism due to chronic renal failure on long term hemodialysis. However, recurrence has been an enigma and therefore, the factors involved in the recurrence of hyperparathyroidism were studied in 128 patients followed for more than 2 years after surgical treatment. The preoperative serum parathyroid hormone (PTH) concentrations correlated with the total weights of the parathyroid glands. When the original autotransplanted glands were divided into two groups, being diffuse and nodular, the rate of recurrent hyperparathyroidism due to graft hyperfunction was significantly higher in the patients who received nodular glands (24%) than in those who received diffuse glands (8.4%) (P<0.05). To investigate whether PTH synthetic activity is different in diffuse and nodular glands, the amount of PTH mRNA was studied by in situ hybridization. There was no significant difference in the amount of PTH mRNA in the cells from either diffuse or nodular glands. These data suggest that the recurrence of hyperparathyroidism is not due to enhanced PTH synthetic activity of autotransplant grafts but to the abnormal growth rate of the transplanted gland.     

Secondary and tertiary hyperparathyroidism: role of preoperative localization

BACKGROUND: The usefulness of both technetium Tc-99m sestamibi (MIBI) scintigraphy and ultrasonography (USG) scan for the detection of enlarged parathyroid glands secondary to renal hyperparathyroidism is rarely addressed. METHODS: A retrospective study from July 1999 to June 2005 was carried out on patients with secondary and tertiary hyperparathyroidism to determine the role of preoperative localization. RESULTS: In the 5 years, 73 patients with renal hyperparathyroidism underwent initial bilateral neck exploration with total parathyroidectomy. Four patients underwent neck exploration with parathyroidectomy for persistent hyperparathyroidism. Two patients underwent neck exploration with parathyroidectomy for recurrent hyperparathyroidism. For patients with initial secondary/tertiary hyperparathyroidism, MIBI scintigraphy correctly showed 101 of 276 (36.6%) surgically confirmed enlarged parathyroids, whereas USG scan showed 99 of 276 (35.9%) surgically confirmed enlarged parathyroids. For persistent or recurrent secondary/tertiary hyperparathyroidism, MIBI scintigraphy and USG scan had sensitivity of 100 and 50%, respectively. CONCLUSIONS: In conclusion, preoperative localization studies have a limited value when used before first neck exploration in secondary/tertiary hyperparathyroidism because of the poor results in identifying all parathyroid glands. In persistent/recurrent hyperparathyroidism, it may play a useful role in localization of the missed or ectopic parathyroid gland.     

甲状旁腺全切除加前臂自体移植术治疗肾性继发性甲状旁腺功能亢进的长期疗效

目的: 探究甲状旁腺全切除加前臂自体移植术（total parathyroidectomy with forearm autotransplantation, TPTX+AT）治疗肾性继发性甲状旁腺功能亢进（secondary hyperparathyroidism, SHPT）术后长期疗效。方法: 我院1999年1月至2017年11月行TPTX+AT的SHPT病人124例,分析术后症状改善和血钙、磷、全段甲状旁腺激素（intact parathyroid hormones, iPTH）水平变化,以及术后复发率、持续性甲状旁腺功能低下发生率、死亡率等。结果: 术后病人临床症状均明显改善。术后1个月病人血钙、磷、iPTH及碱性磷酸酶水平均较术前明显降低（均P<0.05）,基本可长期控制在正常水平。随访至2018年5月,10例（8.06%）复发,7例（5.64%）发生持续性甲状旁腺功能低下,19例（15.32%）死亡。结论: TPTX+AT治疗SHPT能长期有效地缓解症状,改善钙磷代谢。术后复发率与持续性甲状旁腺功能低下发生率、死亡率均在较低水平。     

The calcimimetic cinacalcet normalizes serum calcium in renal transplant patients with persistent hyperparathyroidism.

BACKGROUND: Treatment of persistent hyperparathyroidism in renal transplant patients resistant to calcium and vitamin D sterols is limited and often requires parathyroidectomy. Given the potential hazards linked to surgery, an alternative approach to manage excess parathyroid hormone (PTH) secretion is needed. Calcimimetics inhibit PTH secretion by modulating the calcium-sensing receptor in the parathyroid. Lowering of the serum calcium concentration with the calcimimetic cinacalcet has previously been demonstrated in patients with primary hyperparathyroidism or with secondary hyperparathyroidism on dialysis. Here we present the first clinical observations of a calcimimetic in patients with persistent hyperparathyroidism. METHODS: A 30 mg dose of cinacalcet was prescribed once daily for 3 months to seven female and seven male stable renal transplant patients, aged 23-65 years, 7 months to 14 years after transplantation, with a serum creatinine ranging from 89 to 229 micromol/l and persistent hyperparathyroidism. Concomitant medication included cyclosporin and low-dose prednisone in all patients. RESULTS: On cinacalcet, serum calcium decreased and normalized in all but two patients (baseline 2.72+/-0.03 mmol/l; 1 month 2.42+/-0.04 mmol/l, P<0.001), whereas serum PTH and phosphate levels did not change significantly. A slight reduction in renal function, as assessed by serum creatinine concentration, was observed at months 2 and 3 (P<0.05). An immunoglobulin-deficient patient developed colitis after 1 week of treatment and cinacalcet was withdrawn. No patient stopped cinacalcet because of other presumed side effects. CONCLUSION: Calcimimetics are a promising therapy in renal transplant patients with persistent hyperparathyroidism. Prospective controlled studies must now be designed focusing on functionally relevant musculo-skeletal end-points and allowing the exclusion of negative effects on long-term renal and general outcome of such patients.     

Outcomes in patients with renal hyperparathyroidism requiring cinacalcet pre-operatively followed by parathyroidectomy

Background

Cinacalcet is an effective treatment for renal hyperthyroidism when traditional medical therapy has failed. We studied the impact of pre-operative cinacalcet administration on post-surgical outcomes.

Bone scan of hemodialysis patients with secondary hyperparathyroidism before and after parathyroidectomy

Renal osteodystrophy (ROD) accompanied by long-term hemodialysis patients with chronic renal failure includes several forms of disorders of mineral and skeletal metabolism such as osteitis fibrosa attributed to secondary hyperparathyroidism, osteomalasia and adynamic bone disease. Bone scan is performed to detect of the mainly pathophysiology of ROD. We investigated bone scan of 25 hemodialysis patients with secondary hyperparathyroidism diagnosed clinically before and after parathyroidectomy (PTX). Before PTX an diffusely high accumulation of bone seeking agent in the whole skeleton especially skull in all patients (100%), vertebra in 24 out of 25 (96%), patella in 24/25 (96%), limbs in 23/25 (92%), sternum in 19/25 (76%), sacrum in 18/25 (72%) and costochondral junctions in 14/25 (56%) was noted in these patients. The radionuclide activity of the calvaria, maxilla and mandible in the skull was prominently high. Fourteen patients had an equally high activity in the calvaria, maxilla and mandible, 6 patients had higher activity in the maxilla and mandible than that of calvaria and 5 patients had higher in the calvaria than that of maxilla and mandible. After PTX the changes in the skull were obvious in 19 patients who showed a more markedly decreased in activity of the maxilla and mandible than that of the calvaria. In 3 patients showed a more markedly decreased in activity of the calvaria than that of the maxilla and mandible. Another 3 demonstrated equally decreased in activity in the calvaria, maxilla and mandible. It became clear that the highest activity of the skull was shown in all patients and the therapeutic changes of the skull are the most pronounced in maxilla and mandible in this study.