Advanced Renal Hyperparathyroidism Research Articles

Incidence of Parathyroid Glands Located in Thymus in Patients with Renal Hyperparathyroidism

Parathyroid glands are frequently located in thymus, and it is essential to resect thymic tissue from the neck incision, especially in surgery for renal hyperparathyroidism (HPT). In this study, we evaluated the incidence, location, and type of intrathymic parathyroid glands in 902 patients who underwent initial parathyroidectomy (PTx) for advanced renal HPT in our department. Removal of the thymic tongues on both sides was routinely performed from the neck incision, and the thymic tissue was carefully examined both macroscopically and microscopically. Of the 902 patients in the study, 269 had only inferior parathyroid glands in the thymus, in 62 patients only supernumerary glands were found in the thymic tongue, and in 78 patients both inferior and supernumerary glands were present in thymic tissue. Therefore the incidence of patients with intrathymic glands was 45.3% (269 + 62 + 78 = 409/902). In 129 (92.1%) of 140 patients with supernumerary glands in the thymic tongue, these glands were detected only on histopathological examination, and about half of them were classified as the parathyromatosis type. In the human, parathyroid glands might be located in the thymus in about 50%. If the inferior gland/glands cannot be found around the inferior pole of thyroid lobe, it is very important to search for glands in the thymic tongue. Moreover, to avoid missing supernumerary glands, removal of the thymic tongue on both sides is essential in surgery for renal HPT.

Percutaneous ethanol injection therapy for advanced renal hyperparathyroidism in Japan: 2004 survey by the Japanese Society for Parathyroid Intervention.

Background. Marked hyperplasia of the parathyroid gland (PTG) is a characteristic feature of severe hyperparathyroidism in patients under chronic haemodialysis treatment. Percutaneous ethanol injection therapy (PEIT) is now becoming popular in Japan as a treatment option for secondary hyperparathyroidism (SHPT) and its cost is covered by the National Health Insurance (NHI) System. The Japanese Society for Parathyroid Intervention surveyed its membership in 2004 to revise the guidelines for the use of PEIT.Methods. The project was approved by the Executive Committee of the Society, and the primary questionnaire was addressed to 3268 centres (departments) affiliated with the Japanese Society for Dialysis Therapy. A follow-up questionnaire was sent to all the centres that responded.Results. Although the number of centres to which the questionnaire was sent in 2004 was 3268, compared with 2653 in 1998, the number of responses decreased from 1425 (53.7%) in 1998 to 962 (29.4%) in 2004. To the question of whether the centre performed PEIT, 114 (11.9%) answered ‘Yes’ and 848 (88.1%) answered ‘No’ in 2004. It was an increase from 1998 when only 83 (5.8%) of 1425 centres answered ‘Yes’. In the 1998 survey, 612 patients underwent PEIT at 74 centres, and in 2004, 2098 patients underwent PEIT at 111 centres.Conclusions. PEIT may become the frequently performed treatment for SHPT patients who become resistant to medical therapy. However, the same problems as in 1998 remain unsolved; that is, recurrent nerve paralysis, difficulty of post-PEIT PTx and lack of evidence showing the long-term effectiveness of PEIT.

Two cases of calciphylaxis treated by parathyroidectomy: importance of increased bone formation

Calciphylaxis (calcific uremic arteriolopathy) is a poorly understood and highly morbid syndrome of both vascular calcification and skin necrosis. The main histopathological finding is calcium deposits within arteriolar and small vessel walls, showing endovascular fibrosis associated with fat necrosis. The therapeutic strategy is to normalize the high calcium-phosphate products (Ca x P). When calciphylaxis is complicated with advanced renal hyperparathyroidism (HPT), parathyroidectomy (PTX) should be performed promptly. However, for patients with low PTH level, calciphylaxis is unresponsive to PTX, and such an approach may worsen hyperphosphatemia and hypercalcemia. We report two patients with calciphylaxis confirmed by skin biopsy. PTX was performed in both patients based on high PTH levels. PTH and Ca x P level decreased in both patients post PTX. In Case 1, the skin ulcers gradually improved and almost disappeared after PTX. However, in Case 2, new ulcers appeared after PTX. In Case 1, alkaline phosphatase (ALP) after PTX was approximately twice its level before surgery and PTX resulted in normalization of uptake on bone scintigraphy. However, no rise in ALP was noted in Case 2, probably due to long-term use of aluminum, which prevented bone formation. These findings suggest that differences in the extent of bone formation explain the different response in post-PTX ulcer healing.

Recurrent Renal Hyperparathyroidism Caused by Parathyromatosis

Parathyromatosis is defined as multiple foci of benign hyperfunctioning parathyroid tissue in the neck or mediastinum. Parathyromatosis is a problematic cause of recurrent hyperparathyroidism (HPT). In renal HPT, the stimuli of the parathyroid cells persist after parathyroidectomy (PTx), and for this reason, parathyromatosis might be important in renal HPT. Between July 1973 and December 2005, 1,932 patients underwent PTx for advanced renal HPT in our department. We evaluated the frequency, clinical findings and the prognosis of this kind of parathyroid disorder. After total PTx with forearm autograft for renal HPT, which was performed initially in our department, the risk for developing parathyromatosis was 0.11% (2/1837); after sub-total PTx, it was 5% (1/20). The risk for developing parathyromatosis was lower after total PTx with forearm autograft than after sub-total PTx (P < 0.05). In patients who developed persistent or recurrent HPT and were referred to our department for neck re-operation, parathyromatosis occurred in 12.1% (7/58); in those originally operated on at our hospital, the corresponding figure was 7.1% (3/42). This difference was not significant (P = 0.42). Only in 4 of 10 patients was parathyromatosis suggested before re-operation. However, in spite of several re-operations, high parathyroid hormone (PTH) levels persisted in 6 of 10 patients with parathyromatosis. Parathyromatosis is a non-negligible cause of recurrent renal HPT in patients who require neck re-exploration. Parathyromatosis is difficult to diagnose pre-operatively and completely controlled by re-operation. Parathyromatosis should be kept in mind when performing neck re-exploration for recurrent renal HPT.

Surgical significance of undescended parathyroid gland in renal hyperparathyroidism

In renal hyperparathyroidism, in which basically all parathyroid glands are hyperplastic, overlooking one undescended parathyroid gland becomes important. Between July 1973 and December 2004, 1750 patients in our department underwent parathyroidectomy for severely advanced renal hyperparathyroidism. We evaluated the frequency and location of undescended parathyroid glands and the clinical findings and the prognosis of patients with such glands. Undescended parathyroid glands in our series of renal hyperparathyroidism numbered 16 of 1750 cases (0.91%). In 9 patients, the glands were removed at the initial parathyroidectomy in our hospital. Two of these glands were detected by preoperative imaging; 6 glands were removed with an undescended thymus. The mean weight of the undescended parathyroid glands that were removed at initial operations was 470 mg (30 to 1392 mg). In 7 other patients, unrecognized undescended glands were responsible for persistent hyperparathyroidism in 6 patients and recurrent disease in 1 patient. In 4 of these 7 patients, the initial parathyroidectomy was performed at our hospital; in the other 3 patients, the initial parathyroidectomy had been done at another hospital, and the glands were removed on reoperation. The mean weight of these glands was 1295 mg (range, 444-2396 mg). In 12 of a total of 16 patients with undescended glands, there appeared to be an inferior parathyroid gland, and the other 4 glands appeared to be a superior gland. No glands were detected by sestamibi scans. In operations for renal hyperparathyroidism, an undescended parathyroid gland can be readily overlooked, which leads to persistent or recurrent hyperparathyroidism. Because an undescended parathyroid gland is not always an inferior gland, in surgery for persistent and/or recurrent renal hyperparathyroidism, it is very important to examine carefully the submandibular portion to detect such an undescended gland.

Ultrasonographic Diagnosis and Nucleus Medicine Inspection with 99m-Tec-MIBI for Advanced Renalhyperparathyroidism

Ultrasonographic Diagnosis and Nucleus Medicine Inspection with 99m-Tec-MIBI for Advanced Renalhyperparathyroidism

Calciphylaxis: A Rare Complication of Patients Who Required Parathyroidectomy for Advanced Renal Hyperparathyroidism

Calciphylaxis is a relatively rare but life-threatening complication in uremic patients. Clinical findings and prognosis were evaluated in six patients who developed calciphylaxis from a group of 1499 patients who underwent parathyroidectomy (PTx) for advanced renal hyperparathyroidism (HPT) in our department from July 1972 to July 2003. The frequency of calciphylaxis was 0.40% (6/1499). Two patients were women and four were men. The mean age was 50.5 years, and the mean duration of hemodialysis (HD) treatment was 14.0 years. In five of six patients, calciphylaxis was classified as distal type; in one case, as proximal type. In three patients, calciphylaxis was diagnosed at the time for PTx. In two patients, calciphylaxis was identified after PTx, although the serum parathyroid hormone (PTH) level was within the appropriate range for dialysis patients. In two patients, calciphylaxis improved after PTx, but two patients required leg and toe amputations after PTx. In one patient with the proximal type of calciphylaxis, the condition occurred when a high PTH level recurred after the initial PTx. The patient died as a result of a serious infection due to uncontrollable skin ulcers. Calciphylaxis is a rare complication in patients who require PTx for renal HPT. Especially the proximal type has a poor prognosis. High levels of the Ca x P product and/or PTH are risk factors. Therefore, this syndrome should be kept in mind and attention should be paid to reduce risk factors. It is important that PTx being performed at the right time in patients with advanced renal HPT refractory to medical treatment.

Clinical effect of parathyroidectomy for advanced renal hyperparathyroidism

Advanced renal hyperparathyroidism induced not only osteitis fibrosa but also vessel and valvular calcification which affect high mortality due to cardiovascular disease. Parathyroidectomy usually promises dramatic clinical improvement of hyperparathyroidism. However, ectopic calcification except for tumor calcinosis is irreversible by parathyroidectomy. Then the surgery should be indicated at right time. Total parathyroidectomy with forearm autograft is suitable operative method for renal hyperparathyroidism, because removal of autograft can be less invasively performed at recurrence which is not negligible after the internal operation.

More than 1,000 cases of total parathyroidectomy with forearm autograft for renal hyperparathyroidism

Between March 1981 and December 2000, we performed 1,053 total parathyroidectomies with forearm autograft for advanced renal hyperparathyroidism (HPT). Based on histopathologic and pathophysiologic investigations, surgical treatment should be considered when parathyroid glands show nodular hyperplasia. Measuring parathyroid volume by ultrasonography was useful to detect nodular glands and to determine surgical indications. The clinical effect of parathyroidectomy on the symptoms and biochemical variables was striking. Skeletal deformity, progressive bone loss, and vessel calcification leading to high mortality risk could not be alleviated by even successful surgery, however. To prevent cardiovascular complications, parathyroidectomy should be performed in the relatively early stage of renal HPT. Total parathyroidectomy with forearm autograft is a suitable procedure for renal HPT, especially in patients who require long-term hemodialysis. For surgeons, it is important to remove all parathyroid glands, including supernumerary glands, at the initial operation and to choose adequate parathyroid tissue for the autograft to prevent persistent and recurrent HPT. Although the risk of graft-dependent recurrent HPT is not negligible, enlarged transplanted parathyroid tissue can be removed easily and noninvasively from the forearm under local anesthesia. There is no risk of hypofunction of the autograft. © 2001 by the National Kidney Foundation, Inc.

Management of renal hyperparathyroidism

Histopathological and pathophysiological investigations including the genetic approach have been contributing to management of renal hyperparathyroidism (HPT). In renal failure, parathyroid glands initially proliferate diffusely and polyclonally, and then are transformed to monoclonal nodular hyperplasia with aggressive growth potential and diminished expression of both the vitamin D receptor and calcium-sensing receptor. When more than one parathyroid gland progresses to nodular hyperplasia, HPT is refractory to medical treatment. To prevent advanced renal HPT, progression to nodular hyperplasia should be avoided. Control of hyperphosphatemia is very important to prevent advanced renal HPT, but it is usually difficult. Administration of vitamin D metabolites constitutes the most promising form of prophylaxis and should be performed with monitoring of the PTH level to avoid adynamic bone disease. Calcitriol pulse therapy is effective for advanced renal HPT; however, when parathyroid glands progress to nodular hyperplasia, surgical treatment should be considered. Measuring parathyroid volume by ultrasonography is useful for detecting nodular glands and deciding treatment options. Parathyroidectomy (PTx) is an effective treatment for advanced renal HPT. However, the timing of the operation is important, because the improvement of skeletal deformity and vessel calcification inducing high mortality risk cannot be expected even after successful surgery. Total PTx with forearm autograft is a suitable procedure for renal HPT. Recently. selective percutaneous ethanol injection therapy has been adopted as an alternative treatment to PTx, and new vitamin D analogues, phosphate binders without calcium, and calcimimetics have been developed as new options for management of renal HPT.

Surgical Management of Secondary Hyperparathyroidism in Uremia

Advanced secondary (renal) hyperparathyroidism (HPT) induced by uremia is one of the most serious complications for long-term hemodialysis patients. Parathyroidectomy (PTx) is indicated in patients with severely advanced renal HPT that is refractory to medical treatment, including calcitriol pulse therapy. The clinical effect of PTx is striking. However, skeletal deformity, vessel calcification, and remarkable reduction of bone content is irreversible. Therefore, it is important to perform PTx at the right time. Based on histopathological and pathophysiological investigations, nodular hyperplasia is monoclonal neoplasia with abnormal parathyroid hormone response to extracellular calcium and vitamin D. When parathyroid hyperplasia progresses to nodular hyperplasia, PTx should be required. Total PTx with forearm autograft is the preferred procedure for renal HPT, especially for patients who need to continue hemodialysis treatment after PTx. Removal of all parathyroid glands, including supernumerary glands, at the initial operation and proper choice of adequate parathyroid tissue for autograft are important to prevent persistent and recurrent HPT. In this series of 782 patients, the function of autografted parathyroid tissue is almost satisfactory and no retransplantation of cryopreserved parathyroid tissue was necessary; however, graft-dependent recurrent HPT was not negligible. In conclusion, total PTx with forearm autograft is very effective and adequate treatment for advanced renal HPT and parathyroid function can be controlled after PTx.

Surgical management of secondary hyperparathyroidism in uremia.

Advanced secondary (renal) hyperparathyroidism (HPT) induced by uremia is one of the most serious complications for long-term hemodialysis patients. Parathyroidectomy (PTx) is indicated in patients with severely advanced renal HPT that is refractory to medical treatment, including calcitriol pulse therapy. The clinical effect of PTx is striking. However, skeletal deformity, vessel calcification, and remarkable reduction of bone content is irreversible. Therefore, it is important to perform PTx at the right time. Based on histopathological and pathophysiological investigations, nodular hyperplasia is monoclonal neoplasia with abnormal parathyroid hormone response to extracellular calcium and vitamin D. When parathyroid hyperplasia progresses to nodular hyperplasia, PTx should be required. Total PTx with forearm autograft is the preferred procedure for renal HPT, especially for patients who need to continue hemodialysis treatment after PTx. Removal of all parathyroid glands, including supernumerary glands, at the initial operation and proper choice of adequate parathyroid tissue for autograft are important to prevent persistent and recurrent HPT. In this series of 782 patients, the function of autografted parathyroid tissue is almost satisfactory and no retransplantation of cryopreserved parathyroid tissue was necessary; however, graft-dependent recurrent HPT was not negligible. In conclusion, total PTx with forearm autograft is very effective and adequate treatment for advanced renal HPT and parathyroid function can be controlled after PTx.

Guideline of selective parathyroid percutaneous etanol injection therapy for patients with advanced renal hyperparathyroidism

Guideline of selective parathyroid percutaneous etanol injection therapy for patients with advanced renal hyperparathyroidism

In vitro suppression of parathyroid hormone secretion by 22‐oxa‐calcitriol in human parathyroid hyperplasia due to uraermia

SUMMARY: 22‐oxa‐calcitriol (OCT), a vitamin D analogue, suppresses parathyroid hormone (PTH) secretion and has less calcaemic activity than 1,25‐dihydroxyvitamin D3 [1,25(OH)2D3] in vivo. In this study, we evaluated the effect of OCT on PTH secretion in vitro using human hyperplastic parathyroid tissue obtained during surgery for advanced renal hyperparathyroidism and normal bovine parathyroid glands to compare the effects of 1,25(OH)2D3. 22‐oxa‐calcitriol suppressed PTH secretion by nodular hyperplastic parathyroid tissue and normal bovine tissue in a dose dependent manner, the same as 1,25(OH)2D3. We showed the additive effect of extracellular calcium level on suppression of PTH secretion by OCT and 1,25(OH)2D3. These results suggest that OCT suppresses PTH secretion, the same as 1,25(OH)2D3 not only in normal parathyroid cells but also on hyperplastic parathyroid cells.

Surgical treatment of renal hyperparathyroidism.

Advanced secondary (renal) hyperparathyroidism induced by chronic renal disturbance is one of the most serious complications for long-term hemodialysis patients. Parathyroidectomy is indicated in patients with severely advanced renal hyperparathyroidism refractory to medical treatment (including calcitriol pulse therapy) and the clinical effect of parathyroidectomy is striking. However, skeletal deformity, vessel calcification, and remarkable reduction of bone content is irreversible, and it is important to perform parathyroidectomy at right time. Based on histopathological and pathophysiological investigations, nodular hyperplasia is monoclonal neoplasia with abnormal parathyroid hormone (PTH) response to extracellular calcium and vitamin D. When parathyroid hyperplasia progresses to nodular hyperplasia, parathyroidectomy should be required. Total parathyroidectomy with forearm autograft is the preferable procedure for renal hyperparathyroidism, especially for patients who need to continue hemodialysis treatment after parathyroidectomy. Removal of all parathyroid glands, including supernumerary glands, at the initial operation, and proper choice of adequate parathyroid tissue for autograft, are important to prevent persistent and recurrent hyperparathyroidism. Preoperative image diagnosis is useful for localization, and routine resection of thymic tissue is necessary to remove supernumerary glands. In our series of 548 patients, graft-dependent recurrent hyperparathyroidism was not negligible and the incidence was about 20% at the 5th year postoperatively. Enlarged autografts of parathyroid tissue could be removed from forearm under local anesthesia with fewer invasions. The function of autografted parathyroid tissue is nearly satisfactory and no re-transplantation of cryopreserved parathyroid tissue was necessary. To avoid adynamic bone disease, relatively high PTH level is required-over-suppression of PTH by excess of vitamin D and calcium salts should be avoided. In our experience, total parathyroidectomy with forearm autograft is very effective and adequate treatment for advanced renal hyperparathyroidism, and parathyroid function can be controlled after parathyroidectomy.

Clonal analysis of nodular parathyroid hyperplasia in renal hyperparathyroidism.

Although it is well known that chronic renal failure induces parathyroid hyperplasia, the pathogenesis and development of this parathyroid lesion in this disease are poorly understood. Histopathologically, there is progression from diffuse to nodular hyperplasia, and each nodule consists of a single cell type with aggressive proliferative potential. Pathophysiologic and clinical investigations have suggested that neoplastic tumors may emerge from nodular hyperplasia. In this study the clonality of parathyroid tissue in nodular and diffuse hyperplasia in renal hyperparathyroidism was analyzed by a method based on restriction fragment length polymorphism of the X chromosome-linked phosphoglycerokinase gene and on random inactivation of the gene by methylation. DNA of peripheral lymphocytes was screened in 43 women undergoing parathyroidectomy for advanced renal hyperparathyroidism, and 10 of these patients appeared to be heterozygous. Fourteen specimens from these patients were available for clonal analysis. The analysis showed that all four specimens of diffuse hyperplasia were polyclonal, whereas all seven specimens from nodules in nodular hyperplasia and all three samples representing parathyroid tissue removed from forearm because of graft-dependent recurrence were revealed to be monoclonal. It is likely that the clonal origin of each nodule is independent. These results suggest that in renal hyperparathyroidism parathyroid glands initially grow diffusely and polyclonally, and then the cells in the nodules are later transformed monoclonally and proliferate aggressively. From the present study it can be concluded that nodular hyperplasia represents monoclonal parathyroid neoplasia, which might explain why patients with nodular hyperplasia in renal hyperparathyroidism are refractory to medical treatment, requiring parathyroidectomy. To prevent recurrences, nodular hyperplastic tissue should not be left at surgery.

Surgical treatment of secondary hyperparathyroidism

Secondary hyperparathyroidism is one of the most serious complications for long-term hemodialysis patients. In our department, we performed parathyroidectomies on 215 patients between July 1973 and June 1990. We found that parathyroidectomies on 215 patients between July 1973 and June 1990. We found that parathyroidectomy was an effective treatment for advanced renal hyperparathyroidism and that after total parathyroidectomy with forearm autograft, renal hyperparathyroidism was controllable, even when hyperparathyroidism was progressive. However, the timing of this operation was important, because skeletal deformity and vessel calcification did not improve after parathyroidectomy. There were two problems after parathyroidectomy for secondary hyperparathyroidism. One was persistent hyperparathyroidism due to supernumerary parathyroid glands, particularly those located in the mediastinum, and the other was recurrent hyperparathyroidism. From our clinical and pathohistological investigations, we suspected that the proliferation of parathyroid cells changed with the progress of renal hyperparathyroidism and we found that it was difficult to prevent enlargement of parathyroid glands and recurrence of this problem.