Factors predictive of critical value of hypocalcemia after total parathyroidectomy without autotransplantation in patients with secondary hyperparathyroidism

Background: Severe hypocalcemia is the most dangerous complication occurring after total parathyroidectomy without autotransplantation (TPTX) for secondary hyperparathyroidism (SHPT). We aim to identify the prevalence and potential risk factors of very severe hypocalcemia in patients with SHPT undergoing TPTX.

Methods: From April 2012 to August 2015, 157 patients with SHPT undergoing TPTX were reviewed. The critical value of hypocalcemia (CVH) was postoperative serum Ca²⁺ levels of ≤1.5?mmol/L.

Results: Univariate analysis showed that patients in the CVH group were significantly younger than those in the non-CVH group. Sex ratio was significantly different between the two groups. The CVH group had significantly higher levels of preoperative PTH and ALP. Male sex and preoperative levels of PTH and ALP were significant independent risk factors by logistic regression analysis.

Conclusions: Male sex, preoperative PTH and ALP were significantly associated with CVH in patients with SHPT undergoing TPTX.     

甲状旁腺全切＋自体移植术治疗继发性甲状旁腺功能亢进症疗效分析

目的探讨甲状旁腺全切＋自体移植术(tPTX＋AT)治疗维持性血液透析患者继发性甲状旁腺功能亢进症(SHPT)的有效性、安全性以及术后低钙的危险因素。 方法纳入我院2013年1月至2016年11月因SHPT行tPTX＋AT手术的维持性血液透析患者93例,收集术前术后症状、血钙、磷、碱性磷酸酶(ALP)、全段甲状旁腺激素(iPTH)、病理类型、并发症等临床资料。依据术后24 h血钙水平分为正常血钙组(Ca≥2.11 mmol/L)及低钙血症组(Ca<2.11 mmol/L),应用单因素分析及逐步Logistic回归分析术后早期低钙血症的危险因素。 结果手术成功率92.5%。切除360枚甲状旁腺腺体,异位甲状旁腺10枚。病理结果多为腺瘤样增生(96.4%)。同术前相比,术后血清iPTH、磷、ALP明显下降(P<0.05)。低钙血症是术后最常见并发症,发生率82.8%,血钙水平与术前血钙、年龄正相关(r＝0.300, P<0.01;r＝0.265, P<0.01),与术前iPTH、ALP水平负相关(r＝－0.461, P<0.01;r＝－0.477, P<0.01)。术前低血钙(OR＝0.113, P＝0.045)、高ALP水平(OR＝1.050, P<0.001)、高iPTH水平(OR＝1.002, P＝0.004)是术后早期低钙血症发生的独立危险因素。 结论tPTX＋AT可以安全、有效、快速的降低维持性血液透析患者血清iPTH水平,改善机体的钙磷代谢紊乱,但需重视并积极纠正术后低钙血症。针对存在术前低血钙、高iPTH及高ALP水平等高危因素的患者,术前积极纠正低钙血症可能是预防术后低钙的有效干预方式。     

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.     

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。     

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.     

Increased osteocyte death and mineralization inside bone after parathyroidectomy in patients with secondary hyperparathyroidism

In order to gain insight into the mechanisms underlying the dynamic changes in bone metabolism and bone quality after parathyroidectomy (PTX) in secondary hyperparathyroid patients with high levels of parathyroid hormone (PTH), we performed bone histomorphometric analysis with tetracycline labeling in iliac bone biopsy specimens taken before and after PTX, with special attention paid to osteocytes. At 2 to 4 weeks after PTX, PTH concentrations decreased markedly with evident reductions in bone turnover markers. Histomorphometry revealed that at 2 to 4 weeks following PTX, the osteoclast surface decreased to nearly 0%, with a substantial increase in osteoid volume and a reduction in fibrosis volume. Labeling with tetracycline was observed not only at the mineralization front on the bone surface but also around the osteocyte lacunar walls and canaliculi within both the basic multicellular units (BMUs) and bone structural units (BSUs), suggesting that mineralization was taking place along the lacunocanalicular system after PTX. The tetracycline‐labeled area was much greater in the BSUs than in the BMUs and at the mineralization front, and the tetracycline labeling in the BSUs was markedly increased after PTX compared with that in the low‐ and high‐PTH control groups without PTX. The osteocyte number was decreased significantly after PTX, concomitant with an increase in the number of empty lacunae and a reduction of lacunar volume. Thus the increased osteocyte death and mineralization around the lacunocanalicular system in association with a rapid decline in PTH may underlie the changes in bone metabolism and quality that occur following PTX. © 2010 American Society for Bone and Mineral Research.     

Significance of time-course changes of serum bone markers after parathyroidectomy in patients with uraemic hyperparathyroidism.

BACKGROUND: The increase of bone mineral density in cortical bone after parathyroidectomy is smaller than that in cancellous bone. Changes of serum bone markers reflect those of bone metabolism both in cortical and cancellous bone after parathyroidectomy. The present study was undertaken to investigate changes of histomorphometric parameters of cortical and cancellous bone together and their correlation with those of serum bone markers. METHODS: Iliac bone biopsy was performed before and 1 week after parathyroidectomy in Group I (n = 13), and before and 4 and 12 weeks after in Group II (n = 11). Moreover, changes of histomorphometric parameters of the endocortical, intracortical and periosteal surfaces as well as in cancellous bone were monitored. Serum levels of intact parathyroid hormone and bone markers were measured simultaneously. Results. In cancellous bone, osteoclast surface (Oc.S/BS) decreased to 0% within 4 weeks after parathyroidectomy, while osteoblast surface (Ob.S/BS) transiently increased at 1 week, followed by a reduction at 4 weeks to levels below the pre-surgical level. In cortical bone, Oc.S/BS was not reduced to 0%, while a significant and temporary increase of Ob.S/BS was observed only on the endocortical and intracortical surfaces at 4 weeks, but not at 1 week. Serum bone resorption markers did not completely disappear and significant and sustained increases of bone formation markers were observed until 4 weeks after parathyroidectomy. CONCLUSIONS: Changes of bone formation markers lagged behind those of histomorphometric parameters in cancellous bone because changes of cortical bone were observed later and were incomplete compared with those of cancellous bone.     

Changes in bone turnover after parathyroidectomy in dialysis patients: role of calcitriol administration.

BACKGROUND: Available data on changes in serum levels of bone markers after parathyroidectomy (PTx) in dialysis patients are not uniform. Changes are thought to be due to either a reduction in PTH activity per se or to a direct effect of vitamin D therapy on bone cells. We aimed to verify whether treatment with vitamin D modifies serum levels of markers of bone synthesis (alkaline phosphatase (AP), osteocalcin (BGP), procollagen type I C-terminal peptide (PICP)) and resorption (collagen type I C-terminal peptide (ICTP)) within a period of 15 days in haemodialysis patients with severe secondary hyperparathyroidism following PTx. METHODS: We randomized two groups (A, treatment and B, placebo, 10 patients each) with comparable basal PTH values and measured bone markers 3, 7 and 15 days after surgery. All patients were treated with calcium supplements (i.v. and p.o.), and group A also received calcitriol (2.4+/-1.0 microg/day, p.o.). RESULTS: In both groups, PTx induced significant changes in all the markers evaluated, except for BGP in group B. Compared to basal values, ICTP decreased from 481+/-152 ng/ml in group A and 277+/-126 ng/ml in group B to 267+/-94 and 185+/-71 ng/ml (M+/-SD) respectively, and PICP increased from 307+/-139 ng/ml in group A and 309+/-200 ng/ml in group B to 1129+/-725 and 1231+/-1267 ng/ml (M+/-SD) respectively, within 3 days of surgery. AP values increased after 15 days from 1115+/-734 mU/ml in group A and 1419+/-1225 mU/ml in group B to 1917+/-1225 and 1867+/-1295 mU/ml (M+/-SD) respectively. On the contrary, mean values of BGP were never different from basal levels after PTx in either group. In the two groups, the pattern of changes of all the bone markers after PTx was almost identical. Group A patients predictably required lower doses of oral calcium supplements to correct hypocalcaemia (16. 9+/-5.7 vs 22.1+/-5.0 g/10 days; M+/-SD, P<0.04). CONCLUSIONS: The opposite behaviour of serum PICP and ICTP after PTx, in both the treated and untreated groups suggests that quantitative uncoupling between bone synthesis and resorption is responsible for hypocalcaemia. This phenomenon, as reflected by the evaluated bone markers, is unaffected by calcitriol. Based on our data we conclude that immediately after parathyroid surgery, vitamin D therapy does not influence bone cell activity, but improves hypocalcaemia mainly through its known effect on intestinal calcium absorption.     

Prospective study on dialysis patients after total parathyroidectomy without autoimplant

Aim: Secondary hyperparathyroidism is common in chronic kidney disease. When medical treatment fails, subtotal or total parathyroidectomy with autoimplant is done but both are associated with a high recurrence rate. The third surgical strategy is total parathyroidectomy without autoimplant. We evaluate the outcomes of patients who had total parathyroidectomy with no autoimplant. Methods: Thirteen patients who had total parathyroidectomy without autoimplant were prospectively studied from 1998–2002. Intact parathyroid hormone, biochemistry and bone mineral densities were measured at baseline and serially. All patients had bone biopsies done preoperatively and seven had repeat bone biopsies at a mean of 37.7 months postoperatively. Histomorphometric studies were done for all bone biopsies. Patients were observed for fractures. Results: Five patients were on haemodialysis and eight on peritoneal dialysis. Mean duration of follow up was 68 months. Postoperatively, mean intact parathyroid hormone decreased precipitously and remained within or just above normal. Mean serum calcium phosphate product decreased and remained normal. Out of seven patients who had repeat bone biopsies, two showed reversal of hyperparathyroid bone disease to normal, two had mild hyperparathyroidism, while three had adynamic bone disease. One patient with adynamic bone disease subsequently developed biochemical recurrence of hyperparathyroidism. Serial bone densitometry showed remarkable improvement. There was no fracture. Conclusion: In the studied series of total parathyroidectomy without autoimplant, adynamic bone disease occurred in three out of seven repeat bone biopsies while improvement occurred in the rest. Bone mineral density was much improved and there was no fracture.     

Significance of monitoring Bio-Intact PTH (1-84) during parathyroidectomy for secondary hyperparathyroidism

BACKGROUND: The Bio-Intact PTH (1-84) assay has recently been developed to specifically measure the intact PTH (1-84) molecule, and in this study we used it to investigate sequential changes in serum Bio-Intact PTH (1-84) levels during parathyroidectomy for secondary HPT. MATERIAL AND METHODS: The subjects of this study were 70 patients (41 women, 29 men) who underwent parathyroidectomy between April 2002 and March 2005. Ethylene diamine tetraacetic acid serum samples were drawn via a peripheral venous catheter after induction of anesthesia (basal), and at 5, 10, and 30 min after diseased glands excision. Serum active PTH (1-84) was measured by the Bio-Intact PTH (1-84) assay, which is a two-site chemiluminometric assay. RESULTS: When 4 or more diseased parathyroid glands were removed, the basal of Bio-Intact PTH (1-84) level in patients without persistent HPT (52 cases) was 539 +/- 355 pg/mL. The level of the Bio-Intact PTH (1-84) at 30 min after sufficient parathyroidectomy had decreased to less than 45 pg/mL, whereas the Bio-Intact PTH (1-84) level in patients with persistent HPT at 30 min was greater than 45 pg/mL (3 cases). After removal of three or fewer diseased parathyroid glands (15 cases), the Bio-Intact PTH (1-84) at 30 min in patients without persistent HPT (13 cases) was less than 45 pg/mL. The 2 patients whose the Bio-Intact PTH (1-84) at 30 min was greater than 45 pg/mL underwent reoperation, and residual enlarged parathyroid gland in the neck was removed. CONCLUSIONS: The Bio-Intact PTH (1-84) level at 30 min after parathyroidectomy seems to be useful for judging whether the parathyroidectomy is complete irrespective of the number of glands removed from patients with secondary HPT. When only three diseased parathyroid glands are removed, the surgeon can decide whether to continue or stop neck exploration according to the level of Bio-Intact PTH (1-84) at 30 min.     

Successful implant of long-term cryopreserved parathyroid glands after total parathyroidectomy

BACKGROUND: Parathyroid cryopreservation is essential in some cases of parathyroid surgery. The fate of autografted tissue after long-term cryopreservation is not fully discussed in the literature. METHODS: The successful experience with the use of parathyroid tissues preserved for 21 months and 30 months is reported. RESULTS: Both patients were women with renal hyperparathyroidism who underwent total parathyroidectomy without autotransplantation. Patient 1 was a 40-year-old woman. At 21 months of follow-up, her parathyroid hormone (PTH) level was undetectable, and despite oral calcium supplements, she was hypocalcemic. Forty-five cryopreserved fragments were thawed and implanted in her forearm. Calcium levels improved, and PTH steadily increased in both arms. PTH levels at 18 months after the autograft were 37.0 pg/mL in the contralateral arm and 1150.0 pg/mL in the implant arm. Patient 2 was a 44-year-old woman. After 30 months, her PTH was undetectable, and she underwent cryopreserved tissue implantation. CONCLUSION: These cases show that parathyroid tissue may remain viable even after long-term storage.     

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。     

Total parathyroidectomy without autotransplantation in dialysis patients and renal transplant recipients, long-term follow-up evaluation

Background

Persistent secondary hyperparathyroidism not responding to medication is treated successfully with surgical excision of parathyroid glands (total parathyroidectomy [PTX]). PTX without autotransplantation of parathyroid glands excludes the risk for recurrence of hyperparathyroidism.

Methods

During the years 2002 to 2005, 36 total parathyroidectomies were performed in 33 patients: 21 dialysis patients because of end-stage renal disease and 12 renal transplant recipients.

Results

PTX without autotransplantation was performed successfully in 33 patients, whereas 3 patients were reoperated for remaining parathyroid glands. Immediate improvement of clinical symptoms and a decrease of serum calcium and parathormone levels were observed after surgical procedures. Oral replacement treatment with vitamin D (1a-calcidiol) and calcium was commenced and long-term follow-up evaluation (23.5 ± 7.6 mo) showed that calcium homeostasis was controlled adequately.

Conclusions

PTX without autotransplantation is a safe and effective surgical procedure for the treatment of resistant secondary hyperparathyroidism with immediate response of clinical symptoms. Replacement treatment with vitamin D and calcium provides satisfactory coverage of individual needs.     

Estimated weight of the residual parathyroid gland after parathyroidectomy using plasma levels of the parathyroid hormone

The possibility of estimating the total weight of the parathyroid glands based on the plasma concentration of the parathyroid hormone (PTH) would be of great help when searching for the parathyroid glands during surgery on patients with secondary hyperparathyroidism. Thus, we studied the relationship between the levels of carboxylterminal PTH (C-PTH), midportion PTH (M-PTH) and intact PTH, and the weight of the parathyroid glands resected for secondary hyperparathyroidism. The subjects studied were 11 patients with secondary hyperparathyroidism caused by chronic renal failure. The pre- and post-operative differences in the plasma C-PTH levels and plasma M-PTH levels were significantly correlated with the weight of the resected parathyroid glands (p<0.001 for both), but there was no correlation between the differences in the levels of intact PTH and the weight of the resected parathyroid glands. From these relationships we estimated the weight of the residual parathyroid gland after parathyroidectomy using the levels of each PTH. All patients in whom the residual parathyroid gland was estimated to be heavy based on the levels of M-PTH showed recurrence of hyperparathyroidism after the parathyroidectomy. We therefore found that estimation of the weight of the parathyroid glands from the levels of M-PTH is both possible and useful.     

Cinacalcet is effective in relapses of secondary hyperparathyroidism after parathyroidectomy.

BACKGROUND: Relapses of secondary hyperparathyroidism (SHPTH) after parathyroidectomy (PTx) in haemodialysis patients are relatively frequent. Calcimimetics (cinacalcet HCl) offer a new therapeutic opportunity for their treatment. However, no data about the treatment with cinacalcet of relapses of SHPTH after PTx are available in literature. The aim of this single-centre prospective study was to evaluate the therapeutic efficacy of cinacalcet in this high-risk category of patients. METHODS: Twelve haemodialysis patients of our Dialysis Unit had a relapse of SHPTH after PTx, defined as serum levels of immunoreactive intact parathyroid hormone (iPTH)>300 pg/ml. They were stratified into a treatment group (the six patients having the highest serum levels of iPTH) and a control group (the remaining six patients): the former were treated for 6 months with a dose of cinacalcet ranging from 30 mg every other day to 60 mg a day; the latter continued to be administered the conventional treatment. Serum levels of albumin, iPTH, calcium (Ca), phosphate (P) and alkaline phosphatase were determined monthly. The treatment group included four cases of nodular hyperplasia and two cases of carcinoma of parathyroid glands, whereas the control group included four cases of nodular hyperplasia and two cases of diffuse hyperplasia. RESULTS: At the start of the study, the six patients treated with cinacalcet showed a more severe picture of biochemical abnormalities when compared with the control patients. After 6 months of treatment, a statistically significant reduction in the serum levels of iPTH, Ca, P and CaxP product was obtained only in the patients treated with cinacalcet. Symptomatic episodes of hypocalcaemia (serum Ca<7.0 mg/dl) were observed in three patients of this group. The six patients undergoing the conventional treatment showed at 6 months a not significant decrease in the mean serum levels of iPTH and a not significant increase in the mean serum levels of Ca, P and CaxP product, when compared with the baseline values. CONCLUSIONS: Our single-centre prospective study, even though small and of short duration, shows that cinacalcet is effective also in controlling relapses of SHPTH after PTx, thus representing a solid, and sometimes unique, therapeutic opportunity for this high-risk category of patients.     

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.