Immediate and Long-term results of parathyroid autotransplantation in primary hyperparathyroidism

The authors review the experience of total parathyroidectomy with microsurgical autotransplantation with reference to the long-term results. This method — after further control investigations-may be envisaged for making a definitive evaluation of the results.     

Expression of kinase genes in primary hyperparathyroidism: adenoma versus hyperplastic parathyroid tissue

BACKGROUND: Differentiation between parathyroid hyperplasia and adenoma is difficult and based on the surgeon's skill. Microarrays and other sophisticated research tools generate information about differential gene expression in various tissues. Exploration of genes that express differentially in 1 tissue will enable identification and perhaps development of new methods of preoperative or intraoperative diagnosis. METHODS: RNA was extracted from parathyroid hyperplasia and adenoma tissue and hybridized to a microarray containing 359 human complementary DNAs of known kinase genes. Signals of exposure were scanned and quantified with software for digital image analysis (Atlas-image, v. 2; Clontech Labs Inc, Palo Alto, Calif). The program generates a color schematic comparison view and numeric data in a tabular format for further analysis. RESULTS: The ratio values that are considered significant (< 0.5 or > 1.5) suggest that genes up-regulated in parathyroid adenoma are those responsible for angiogenesis and production of blood vessels. Genes down-regulated in parathyroid adenoma and expressed in hyperplasia are related to a decrease in apoptosis. Moreover, an interesting gene expressed only in the hyperplasia sample is increased in relation to in vivo proliferation activities. CONCLUSIONS: Parathyroid hyperplasia and adenoma are different physiologic conditions. Further analysis of kinase genes involved in angiogenesis and apoptosis will enable design of a chip that concentrates in the different key genes responsible for the transition between hyperplasia and adenoma. Identifying such genes will enable to target both diagnostic and therapeutic approaches.     

Acute hyperparathyroidism successfully treated by total parathyroidectomy and parathyroid autotransplantation

Acute hyperparathyroidism occurs infrequently and sometimes represents a diagnostic problem in urological patients.We report a case of acute hyperparathyroidism successfully treated by total parathyroidectomy and parathyroid autotransplantation.     

Total parathyroidectomy with autotransplantation for a rare disease derived from uremic secondary hyperparathyroidism,the uremic leontiasis ossea

Summary

We described six uremic leontiasis ossea (ULO) patients who underwent total parathyroidectomy with autotransplantation. ULO demonstrated more a systemic disease than a simple craniofacial deformation. The surgery seemed an effective treatment to alleviate secondary hyperparathyroidism and to improve patients’ quality of life. ULO may have a high postoperative recurrence tendency.

Introduction

ULO is a rare disease derived from uremic secondary hyperparathyroidism (SHPT). Previous studies mostly focused on the craniofacial deformations. This study aims to investigate the systemic features of the disease and the surgical outcomes.

Methods

The present study retrospectively assessed six ULO patients who underwent total parathyroidectomy (TPTX) with autotransplantation (AT). Follow-up data were recorded. The follow-up status was considered as “effectiveness” if serum intact parathyroid hormone (iPTH) levels were <150 pg/mL in the first 3 days after surgery, or as “recurrence” if serum iPTH gradually increased >300 pg/mL during follow-up in patients whose status was initially considered as “effectiveness”.

Results

Craniofacial deformations, short stature, thoracocyllosis, spine malformations, osteodynia, and muscle weakness were observed in all patients. Abnormal pulmonary functions were observed in five patients. After surgery, one patient died from respiratory failure. Surgery was effective in the remaining five patients with relieved osteodynia and stopped craniofacial deformation. A mean follow-up of 7.6 (4 to 12) months was available. Three patients suffered from recurrence of hyperparathyroidism originating from autografts.

Conclusions

Our data suggests that ULO is not only a simple disease with craniofacial malformations but is a severe systemic disease leading to increased surgical risks. TPTX with AT seems an effective treatment to relieve SHPT and to improve quality of life. ULO may have a high postoperative recurrence tendency.     

肾性甲状旁腺功能亢进患者甲状旁腺素钙敏感受体的表达

目的研究肾性甲状旁腺功能亢进(甲旁亢)患者甲状旁腺组织钙敏感受体(CaR)的表达,探讨CaR在肾性甲旁亢发病机制中的作用。方法用免疫组织化学的方法,比较正常对照组和继发性甲旁亢(SHPT)组甲状旁腺CaR蛋白质的表达。结果CaR在正常甲状旁腺组织的细胞膜和细胞浆均有表达,细胞阳性率为(75．20±2．31)％,而SHPT组为(27．88±4．90)％,明显减少(P＜0．01)。弥漫性增生和结节性增生之间差异也有显著性[分别为(40．00±3．34)％和(15．75±1．75)％,P＜0．01]。CaR表达阳性率与腺体重量呈负相关(r＝0．86,P＜0．01)。结论严重肾性甲旁亢患者甲状旁腺CaR表达明显下降,结节性增生比弥漫性增生下降更显著,是引起PTH过度分泌的重要原因。上调CaR的表达或激活CaR的功能将成为肾性甲旁亢新的治疗目标。     

Apoptosis in parathyroid hyperplasia of patients with primary or secondary uremic hyperparathyroidism

BACKGROUND: Chronic oversecretion of parathyroid hormone (PTH) is associated with parathyroid hyperplasia, reflecting a disturbed balance between cell proliferation and apoptosis. This study addressed the unsolved issue of apoptosis in hyperparathyroidism. METHODS: Parathyroid glands from 19 patients with primary (1 degrees ) and 11 patients with secondary (2 degrees ) uremic hyperparathyroidism, as well as 13 normal parathyroid glands, were examined. Apoptosis was evaluated by terminal deoxynucleotidyl transferase (Tdt)-mediated dUTP nick end-labeling assay (TUNEL). Because the apoptotic process is regulated by several oncoproteins, the expression of Bcl-2 and Bax was analyzed by immunohistochemistry. RESULTS: The numbers of apoptotic cells in 1 degrees parathyroid adenoma (0.99 +/- 0.03 per 1000 cells, mean +/- SE, P < 0.009) and 2 degrees parathyroid hyperplasia (1.20 +/- 0.54 per 1000 cells, P < 0.005) were significantly higher than in normal parathyroid tissue (0.13 +/- 0. 06 per 1000 cells). Light microscopy examination of hyperplastic parathyroid tissue from a uremic patient showed the presence of nuclei with dense chromatin characteristic of apoptosis. Bcl-2 staining was strong in normal tissues but weak or negative in several sections of 1 degrees and 2 degrees hyperparathyroid tissues, mostly in nodular areas. Bax staining was homogeneous in normal tissue but patchy in several hyperplastic tissues. CONCLUSION: These results suggest that hyperparathyroidism is associated with a compensatory increase in apoptosis, possibly favored by a diminished Bcl-2/Bax ratio. This renders highly improbable the hypothesis that parathyroid hyperplasia is due to a decreased rate of apoptosis.     

肾性甲状旁腺功能亢进患者甲状旁腺细胞增生与凋亡

目的　探讨甲状旁腺细胞增生和凋亡在严重肾性继发性甲状旁腺功能亢进（ Ｓ Ｈ Ｐ Ｔ） 发病机制中的作用。方法　对５ 例伴严重 Ｓ Ｈ Ｐ Ｔ的尿毒症患者的腺体,采用 Ｄ Ｎ Ａ 片段末端标记作细胞凋亡的定量检测,并用免疫组织化学法观察增殖细胞核抗原（ Ｐ Ｃ Ｎ Ａ） 、 Ｂｃｌ２ 蛋白质表达。结果　 Ｓ Ｈ Ｐ Ｔ组甲状旁腺腺体细胞凋亡指数（１１ ±１２） 较对照组（７１ ±５６） 明显下降,结节性增生组织比弥漫增生组织更为显著。腺体细胞 Ｐ Ｃ Ｎ Ａ 阳性率（６１０ ‰±３７７ ‰） 比对照组（１５６ ‰±１４０ ‰） 显著增加, Ｂｃｌ２ 表达（０９３ ‰±０４８ ‰） 比对照组（０４４ ‰±０３２ ‰） 亦上调;后两者与腺体细胞凋亡程度均呈负相关。结论　尿毒症时甲状旁腺腺体细胞增生与凋亡失去平衡可能是导致 Ｓ Ｈ Ｐ Ｔ 发生的主要原因     

Decreased calcium-sensing receptor expression in hyperplastic parathyroid glands of uremic rats: role of dietary phosphate

BACKGROUND: The abnormal control of parathyroid hormone secretion in chronic renal failure is attributed, in part, to down-regulation of the calcium-sensing receptor (CaR) in hyperplastic parathyroid tissue. The cause of this down-regulation is unknown. Here we examined the roles of uremia and parathyroid hyperplasia on parathyroid gland (PTG) CaR expression in the rat model of renal failure. METHODS: Rats made uremic by 5/6 nephrectomy were maintained for one month on diets containing 0.2% P (low phosphate), 0.5% P (normal phosphate) or 1.2% P (high phosphate); intact rats (controls) were maintained on the normal-phosphate diet. RESULTS: CaR mRNA was reduced only in uremic rats fed the high-phosphate diet (55% less than in controls, P < 0.05). Immunohistochemical staining revealed decreased CaR protein expression in uremic high-phosphate rat PTG compared with controls (41% decrease as determined by computer-assisted quantitation, P < 0.01). PTG size was increased in uremic rats fed the high-phosphate diet compared with controls (2.77 +/- 0.95 vs. 0.77 +/- 0.16 microgram/g body wt, P < 0.0001). There was no increase in PTG size in uremic rats fed the low-phosphate and normal-phosphate diets (0.92 +/- 0.31 and 1.01 +/- 0.31 micrograms/g) compared with controls (0.77 +/- 0.16 microgram/g body wt). Immunohistochemical staining for proliferating cell nuclear antigen in hyperplastic PTG from uremic rats showed that CaR was decreased primarily in areas of active cell proliferation. CONCLUSION: These results suggest that CaR down-regulation cannot be attributed to uremia per se, but rather, is associated with parathyroid cell proliferation. Furthermore, dietary phosphate restriction prevents both the parathyroid hyperplasia and decreased CaR expression in renal failure.     

Reoperative parathyroid surgery for primary hyperparathyroidism caused by multiple-gland disease: total parathyroidectomy and autotransplantation with cryopreserved tissue

Between September 1975 and June 1980, 27 patients with primary hyperparathyroidism caused by multiple-gland disease underwent reoperative parathyroid surgery at the National Cancer Institute. In an effort to minimize persistence and recurrence we adopted a strategy of attempting total parathyroidectomy. Immediate autotransplantation was not performed, but rather tissue was assessed in vitro for suppressibility and was cryopreserved. Patients with prolonged postoperative hypoparathyroidism underwent autotransplantation with cryopreserved tissue. Of 26 surviving patients, 23 (88%) were cured of hypercalcemia. Although 13 had hypoparathyroidism at the time of discharge, 4 of these 13 no longer required calcium or vitamin D within 1 year. At follow-up 17 were normocalcemic without medication (14 without and 3 with autografts). Thirteen patients had four or five glands removed. Two of these remain hypercalcemic, and at follow-up nine were normocalcemic without medication (seven without and two with autografts). Patients with multiple-gland disease, even those undergoing total parathyroidectomy, remain at risk for persistent or recurrent hypercalcemia. Such patients do no inevitably acquire hypoparathyroidism, and normocalcemia in patients undergoing immediate autotransplantation need not be attributed to the autograft. Selective, deferred autotransplantation with cryopreserved tissue prevents confusion regarding the source of postoperative hypercalcemia should it occur, minimizes the risk of graft-dependent hypercalcemia by restricting autotransplantation to those truly in need of additional tissue, and can effectively manage hypoparathyroidism.     

Total parathyroidectomy and autotransplantation of parathyroid tissue for renal hyperparathyroidism. A one- to six-year follow-up.

From 1975 to 1981 total parathyroidectomy and parathyroid autotransplantation were carried out in 62 patients for renal (secondary) hyperparathyroidism. The paper reports on 46 patients followed for one to six years (mean 2.2 +/- 1.2 years). Forty-one were on chronic hemodialysis, three were predialytic, two had a functioning renal graft. There have been two different groups of indications: one in which hypercalcemia was the main reason for surgery (59%), the other in which severe renal osteopathy (bone pain, radiologic and histologic signs, elevation of alkaline phosphatase, and parathyroid hormone) was observed. Among 45 patients not previously operated on for hyperparathyroidism, five parathyroid glands were removed in three patients, four glands were removed in 36 patients, and three glands were removed in five patients. In one patient previously operated (thyroid surgery), two glands were removed. Tissue was immediately autografted into a forearm muscle. One patient (two glands removed) received a cryopreserved tissue six months after neck exploration. An improvement of bone pain, pruritus, and radiologic signs of renal osteopathy was noted in about 80% of patients. At one to six years no patient was hypercalcemic, in 44 patients the grafted tissue was functioning normally after an average time of 5.8 +/- 1.4 months. One patient is still on low-dose, supplemental therapy for slight hypocalcemia 14 months after autotransplantation. In another patient a part of the grafted tissue was removed for increasing parathyroid hormone levels. Serum concentration of alkaline phosphatase and serum parathyroid hormone decreased after surgery. One- to six-year results after total parathyroidectomy and autotransplantation for renal hyperparathyroidism are considered to be extremely satisfactory.     

Recurrent hyperparathyroidism due to peroperative seeding of neoplastic or hyperplastic parathyroid tissue. Case report

The clinical course and histologic characteristics of recurrent hyperparathyroidism due possibly to peroperative seeding of parathyroid cells are described in four cases--two of parathyroid adenoma, one of parathyroid hyperplasia associated with multiple endocrine neoplasia type 1 and one of parathyroid carcinoma. The observations underline the necessity for careful handling of parathyroid lesions during extirpation, and that the multiple nodules of implanted parathyroid tissue can be curatively excised in some cases.     

Obligatory parathyroid autotransplantation in thyroid surgery

In a series of 301 bilateral thyroidectomies carried out over a 6 month period, immediate parathyroid autotransplantation was performed in 44 patients, i.e. 14.6%. Hypoparathyroidism was transient in 14 patients, i.e. 4.7% but was permanent in 4 patients, i.e. 1.3%. We attempted to determine the conditions justifying parathyroid autotransplantation during thyroidectomies. In our opinion parathyroid autotransplantation should be performed only to save a parathyroid gland accidentally removed or devascularized. It should not be used simply as a means of avoiding dissection no matter how long or tedious.     

7-84 parathyroid hormone fragments are proportionally increased with the severity of uremic hyperparathyroidism

AIMS: Recent progress in PTH assay has revealed that the intact PTH assay kit in current use does not differentiate between the truncated 7-84 PTH molecule and the 1-84 PTH molecule. In our series, we examined the effectiveness of a new PTH assay as a noninvasive method of evaluating severity of uremic hyperparathyroidism. METHODS AND MATERIALS: Two hundred and seventy hemodialysis (HD) patients recruited from three HD centers were included and divided into subgroups according to the conventional iPTH assay results. Pre-dialysis blood samples were collected and subjected to two different PTH assays: "intact" PTH assay (iPTH) and "whole" PTH (wPTH) assay. Two biochemical markers of bone remodeling were also examined. RESULTS: In all cases, PTH levels determined by the wPTH assay were in the average 32.3% lower than those determined by the iPTH assay. The difference of the results of the two PTH assay methods, which indicated the portion of 7-84 PTH fragments of the total PTH molecules measured with the iPTH assay, was gradually increased while the severity of uremic hyperparathyroidism increased. Biochemical markers of bone formation/resorption showed a similar change. CONCLUSION: The portion of the 7-84 PTH fragments and markers of increased bone turnover increased in proportion to the severity of uremic hyperparathyroidism. This finding disproves the hypothetical role of 7-84 PTH fragments alone as the noninvasive marker of low-turnover bone disease in HD patients.     

Assessment of parathyroid autotransplantation for preservation of parathyroid function after total thyroidectomy

BACKGROUND: Hypoparathyroidism with permanent hypocalcemia is a well-recognized complication after thyroid surgery. AIM: This study was conducted to assess the role of immediate parathyroid autotransplantation in the preservation of parathyroid function after total thyroidectomy. PATIENTS AND METHODS: Twenty-eight patients had autotransplantation of parathyroid glands resected or devascularized during total thyroidectomy. Data were collected prospectively regarding demographics, indication for surgery, operative procedure, pathologic diagnosis, number of glands transplanted, and subsequent course. Thyroid nodules were evaluated by ultrasonography, radionuclide scanning, and/or fine-needle aspiration cytology. All patients had serum ionized calcium, phosphorus, and intact parathyroid hormone (PTH) levels measured preoperatively and monitored regularly postoperatively for a period of 14 weeks and again at 6 months after operation. Patients were categorized into three groups according to the number of glands transplanted: one (group 1, n = 6), two (group 2, n = 14), or three glands (group 3, n = 8). In three other volunteers, one parathyroid gland was transplanted in the brachioradialis and subjected to electron microscopy 1, 2, and 4 weeks after transplantation. RESULTS: Total thyroidectomy was performed for malignant disease in 16 patients (57.1%) and for benign disease in 12 (42.9%) patients. All patients reverted to asymptomatic normocalcemia without the need for any medications within 4 to 14 weeks. Normal levels of serum markers were regained slower when one gland was transplanted compared with two or three glands (P <.01). Electron microscopic examination showed evidence of ischemic degeneration in the transplanted tissues 1 week postoperatively. Regeneration started by the second week and coincided with normalization of PTH levels. Optimum resting and nearly normal status of parathyroid tissue was achieved by the fourth week. CONCLUSIONS: This study showed that active PTH production coincides with regeneration of parathyroid cells and that autotransplantation of at least two resected or devascularized glands during total thyroidectomy nearly eliminates permanent postoperative hypoparathyroidism, thus improving the safety of total thyroidectomy performed for malignant or benign disease.     

Total parathyroidectomy with autotransplantation in secondary hyperparathyroidism

Five patients with chronic renal failure were undergone total parathyroidectomy and immediate autotransplantation into the muscle of the forearm. All patients had relief of symptoms and restoration of PTH levels to normal. This technique of parathyroid transplantation offers the surgeon versatility in managing patients with hyperparathyroidism.     

New therapies for uremic secondary hyperparathyroidism.

Secondary hyperparathyroidism (SHPT) is a common and serious complication of chronic kidney disease (CKD). It affects more than 300,000 end-stage renal disease patients treated by dialysis and probably more than 3 million patients with CKD worldwide. For a long time, traditional therapies for SHPT had consisted of correcting the hypocalcemia using calcium salts and vitamin D derivatives, preventing the hyperphosphatemia by calcium- or aluminum-containing intestinal phosphate binders, and recently by using no metal-containing intestinal phosphate binders; however, these therapies are limited by the occurrence of hypercalcemia, hyperphosphatemia, and the lack of specificity and long-term efficacy. Moreover, surgical parathyroidectomy (PTX), which remains the gold standard therapy, is not exempt from risk. PTX exposes patients to anesthesia risks, presurgical and postsurgical complications, and in many cases a permanent state of hypoparathyroidism. Thus, the medical treatment of SHPT became an ideal target for the development of new therapies and strategies. The purpose of this article is to provide an overview of these new therapies, including vitamin D analogs, intestinal phosphate binders, calcimimetics, parathyroidectomies, tyrosine kinase inhibitors, azydothymidine, anticalcineurins, N-terminal truncated parathyroid hormone fragments, bisphosphonates, calcitonin, osteoprotegerin, and others. The use of these new therapies alone or in combination may help to optimize the future treatment of SHPT in CKD patients.     

腔镜下甲状旁腺全切加自体前臂移植术在继发性甲旁亢中的应用

目的:探讨腔镜下甲状旁腺全切术加自体前臂移植术在继发性甲旁亢中的临床应用价值。方法:2013年6月至2015年6月为收治的15例继发性甲状旁腺功能亢进患者行腔镜下甲状旁腺全切加自体前臂种植术,对其临床资料进行回顾性分析。结果:15例患者均完成腔镜手术,无一例中转开放手术。手术时间平均(95.4±20.7)min,术中出血量平均(15.7±6.3)ml,平均下床时间(1.2±0.6)d,术后平均住院(2.6±1.1)d。术后患者骨痛、瘙痒症状明显缓解,无一例发生术后出血、声音嘶哑、呛咳等并发症。1例患者术后发生手脚麻木,经补充钙制剂后症状缓解。随访中,1例患者于术后4个月甲状旁腺激素轻度升高,无其他不适症状,予以继续随访。结论:腔镜下甲状旁腺全切加自体前臂移植术具有患者创伤小、痛苦轻、康复快及美容效果好等优点,并可借助良好的照明、清晰的术野减少出血及神经损伤等并发症的发生,值得推广应用。     

Reoperative parathyroid surgery for persistent hyperparathyroidism

In a 2-year period 30 patients with persistent hyperparathyroidism following 59 prior unsuccessful procedures underwent reoperation. Preoperative arteriography was useful in planning the surgical approach in 56%, and retrospectively was correct in 63%. Selective venous catheterization gave localizing information in 83%, correctly predicting site or side in 60% of the total. Computerized axial tomography was helpful in identifying mediastinal glands before operation. Reoperation was successful in rendering the patient hypocalcemic or normocalcemic in 83%. Of the 11 patients (37%) who were rendered profoundly hypocalcemic, two were subsequently weaned from vitamin D and calcium support; seven have received either fresh or cryopreserved parathyroid autografts. Persistent hyperparathyroidism is a difficult surgical problem which we believe warrants aggressive localization attempts prior to operation. Autotransplantation with cryopreserved parathyroid tissue may be of value in the long-term management of the high incidence of postoperative hypocalcemia in this patient group.