Recurrent Renal Hyperparathyroidism Research Articles

Outcomes of subtotal parathyroidectomy for renal hyperparathyroidism

BackgroundRenal hyperparathyroidism due to end-stage kidney disease is associated with considerable morbidity, and when refractory is treated with parathyroidectomy. Recurrent renal hyperparathyroidism is a major surgical complication, yet initial target parathyroid remnant size and outcomes, including rates of recurrence are not well elucidated. MethodsThis is a single-institution retrospective cohort study of patients who underwent initial subtotal parathyroidectomy for renal hyperparathyroidism on dialysis, from 1990–2022. The subtotal parathyroidectomy was defined as resection of 3 parathyroid glands ± partial resection of the fourth gland leaving a remnant of ∼75–100 mg, and postresection intraoperative parathyroid hormone goal was 150–250 pg/mL. Clinical data were examined for outcomes. ResultsAmong 204 patients who met inclusion criteria, 139 (68%) had follow-up data; 58% (80/139) were women and median age was 45 years. Surgical complications included 2 hematomas (1.4%), 1 recurrent laryngeal nerve injury (<1%), and no patient required readmission for intravenous calcium. Using a target remnant size of 75–100 mg, recurrent renal hyperparathyroidism was uncommon (14/139, 10%) and arose at a median interval of 58.6 months (range, 8–180). In cases of recurrence, the postresection intraoperative parathyroid hormone level was less likely to drop <250 pg/mL (40%, 4/10 vs nonrecurrence 65%, 80/123; P = .11) with a slightly lower median decrease (70% vs 81% in nonrecurrence, P = .8); however, neither were significant. Recurrence did not occur in the 19 patients who later received kidney transplantation (P = .2). ConclusionIn subtotal parathyroidectomy for renal hyperparathyroidism, use of a target 75–100 mg remnant size results in low complication rates. Durable cure appears to be more likely with renal transplantation.

Neck Reoperation for Recurrent or Persistent Renal Hyperparathyroidism.

Patients with renal hyperparathyroidism undergoing parathyroidectomy may experience relapse. Reoperation for persistent or recurrent disease, particularly in the neck region, is challenging and has a high complication rate because of difficult exploration. We aimed to evaluate the effectiveness of neck reoperation in renal hyperparathyroidism. Patients with recurrent or persistent renal hyperparathyroidism who underwent neck reoperation between January 2015 and August 2022 were investigated, focusing on operative findings, perioperative biochemical changes, and significance of intraoperative parathyroid hormone (PTH) measurements. During reoperation, 35 parathyroid glands were identified and removed from the 26 enrolled patients, with one, two, and three glands retrieved from 19 (73.2%), five (19.2%), and two (7.6%) patients, respectively. Most removed glands (68.6%) were located in the lower neck, followed by the mediastinum, carotid sheath, and upper neck. Successful resection, defined as a postoperative PTH level of <300pg/mL, was achieved in 21 patients (80.8%). The remaining four (15.4%) and one (3.9%) patients were classified as having persistent and recurrent disease, respectively. The extent of PTH reduction was correlated with specimen weight, specimen volume, and preoperative alkaline phosphatase (ALP) level. The mean intraoperative PTH ratio (10 min after excision/pre-excision) was 0.23, and all patients with persistent or recurrent disease had a PTH ratio >0.3. Severe hypocalcemia (<7.5mg/dL) occurred in 19 (73.0%) patients after reoperation. Neck reoperation is an effective therapeutic option in patients with recurrent or persistent renal hyperparathyroidism. A decrease in PTH level by >70% during reoperation (PTH ratio <0.3) predicts successful resection.

Intact parathyroid hormone levels localize causative glands in persistent or recurrent renal hyperparathyroidism: A retrospective cohort study.

Persistent or recurrent renal hyperparathyroidism may occur after total parathyroidectomy and transcervical thymectomy with forearm autograft under continuous stimulation due to uremia. Parathyroid hormone (PTH) levels may reflect persistent or recurrent renal hyperparathyroidism because of the enlarged autografted parathyroid glands in the forearm or remnant parathyroid glands in the neck or mediastinum. Detailed imaging requires predictive localization of causative parathyroid glands. Casanova and simplified Casanova tests may be convenient. However, these methods require avascularization of the autografted forearm for >10 min with a tourniquet or Esmarch. The heavy pressure during avascularization can be incredibly painful and result in nerve damage. An easier method that minimizes the burden on patients in addition to predicting the localization of causative parathyroid glands was developed in this study. Ninety patients who underwent successful re-parathyroidectomy for persistent or recurrent renal hyperparathyroidism after parathyroidectomy between January 2000 and July 2019 were classified according to the localization of causative parathyroid glands (63 and 27 patients in the autografted forearm and the neck or mediastinum groups, respectively). Preoperatively, intact PTH levels were measured from bilateral forearm blood samples following a 5-min avascularization of the autografted forearm. Cutoff values of the intact PTH ratio (intact PTH level obtained from the non-autografted forearm before re-parathyroidectomy/intact PTH level obtained from the autografted forearm before re-parathyroidectomy) were investigated with receiver operating characteristic curves to localize the causative parathyroid glands. Intact PTH ratios of <0.310 with an area under the curve (AUC) of 0.913 (95% confidence interval [CI]: 0.856–0.970; P < 0.001) and >0.859 with an AUC 0.744 (95% CI: 0.587–0.901; P = 0.013) could predict causative parathyroid glands in the autografted forearm and the neck or mediastinum with diagnostic accuracies of 81.1% and 83.3%, respectively. Therefore, we propose that the intact PTH ratio is useful for predicting the localization of causative parathyroid glands for re-parathyroidectomy.

Application of Tissue Aspirate Parathyroid Hormone Assay for Imaging Suspicious Neck Lesions in Patients with Complicated Recurrent or Persistent Renal Hyperparathyroidism.

Background: Comprehensive pre-reoperative localization is essential in complicated persistent or recurrent renal hyperparathyroidism. The widely used imaging studies sometimes lead to ambiguous results. Our study aimed to clarify the role of tissue aspirate parathyroid hormone (PTH) assay with a new positive assay definition for imaging suspicious neck lesions in these challenging scenarios. Methods: All patients with complicated recurrent or persistent renal hyperparathyroidism underwent parathyroid sonography and scintigraphy. Echo-guided tissue aspirate PTH assay was performed in suspicious lesions revealed by localization imaging studies. The tissue aspirate PTH level was determined by an immunoradiometric assay. We proposed a newly-developed definition for positive assay as a washout level higher than one-thirtieth of the serum PTH level obtained at the same time. The final diagnosis after re-operation was confirmed by the pathologists. Results: In total, 50 tissue aspirate PTH assays were performed in 32 patients with imaging suspicious neck lesions, including discrepant results between scintigraphy and sonography in 47 lesions (94%), unusual locations in 19 lesions (38%), multiple foci in 28 lesions (56%), and locations over previously explored areas in 31 lesions (62%). Among 39 assay-positive lesions, 13 lesions (33.3%) were not identified by parathyroid scintigraphy, and 28 lesions (71.8%) had uncertain parathyroid sonography findings. The final pathology in patients who underwent re-operative surgery proved the tissue aspirate PTH assays had a 100% positive predictive value. Conclusions: Our findings suggest tissue aspirate PTH assay with this new positive assay definition is beneficial to clarify the nature of imaging suspicious lesions in patients with complicated persistent or recurrent renal hyperparathyroidism.

Radio-guided parathyroidectomy for recurrent renal hyperparathyroidism caused by graft hyperplasia

Radio-guided surgery offers several advantages in treatment of primary hyperparathyroidism. It is considered less helpful in renal hyperparathyroidism, but it could be of great advantage in the treatment of persistent or recurrent secondary hyperparathyroidism. One of the surgical options for symptomatic renal hyperparathyroidism is total parathyroidectomy with autotransplantation of hyperplastic parathyroid tissue in forearm muscles or sternocleidomastoid muscle. Recurrence can occur and is most likely caused by graft hyperplasia. In this report we present the case of 54-year-old woman with recurrent renal hyperparathyroidism caused by hyperplasia of the graft in sternocleidomastoid muscle. Unfortunately no sutures or clips were placed at initial surgery to identify the location of the parathyroid tissue. The preoperative assessment consisting of 99mTc-sestamibi scintigraphy identified a parathyroid tissue in the in the middle third of sternocleidomastoid muscle. The patient underwent a radio-guided neck re-exploration that allowed a rapid localization and excision of the hyperplastic graft.

Parathyromatosis Coexisting with Papillary Thyroid Microcarcinoma

Summary: The aim of this report is to describe a fortuitely discovered association between parathyromatosis and papillary thyroid microcarcinoma. Case description: A 56 year old woman presented with a pyelic relapsed stone, bone pains, neurovegetative complaints and iPTH = 348 ng/l as manifestations of recurrent primary hyperparathyroidism after a right inferior parathyroid adenoma exeresis done elsewere six years ago. Ultrasonography showed a 5 mm hypoechoic zone at the lower pole of the right lobe of the thyroid. At the operation an irregular, unbounded, white-yellowish mass 5 mm in diameter was identified lateral and below the thyroid pole together with 15-20 nodules of 1-2 mm scattered on the distal surface of the gland and also in the areolar fibrofatty surrounding atmosphere. Excision and biopsy of the mass and of two main nodules showed the presence of parathyroid issue and the operation is finally completed to a thyroid lobectomy. Definitive paraffin examination evidencied multiple poorly outlined nests of benign parathyroid tissue but also a minute foci of papillary thyroid carcinoma. Two years after the operation the patient is symptom free without any local recurrence and in normal biological parameters. Discussion: Coexistence between parathyromatosis - a rare but challenging cause of hyperparathyroidism – and thyroid (micro) carcinoma a more frequent encountered lesion is an entirely coincidental occurrence. The preoperative diagnosis of both conditions - particularly of the latter one – is rarely anticipated. In such intraoperative fortuitous finding the intervention must include an en bloc thyroid lobectomy together with periglandular and retro-sternal fibrofatty tissue. This strategy is beneficent also for the eventually nonidentified thyroid microcarcinoma. Conclusions: Preoperative and intraoperative evaluation for recurrent primary and renal hyperparathyroidism must be exhaustive considering possible coexisting thyroid lesions. Indeed in our knowledge there have been no reports in the literature mentioning this unprecedented entity.

Removal of Autografted Parathyroid Tissue for Recurrent Renal Hyperparathyroidism in Hemodialysis Patients

Recurrent renal hyperparathyroidism (HPT) is a serious problem after parathyroidectomy (PTx). We evaluated the frequency of graft-dependent recurrent HPT and the clinical outcomes after removal of the autograft. Between March 1980 and January 2009, 2660 patients underwent total PTx with forearm autograft. After resection of all parathyroid glands, 30 pieces of 1 x 1 x 3 mm parathyroid tissue from diffuse hyperplasia, if possible, were autografted into brachioradial muscle. Graft-dependent recurrence of HPT was diagnosed by a high PTH gradient and detection of swollen autografts by palpation and/or MRI or US. In 248/2660 (9.3%) patients, removal of the graft was required a total of 327 times (53 patients required removal of the autograft several times). The cumulative frequency of graft-dependent recurrent HPT was 17.4% ten years after the initial PTx. Thirty-two patients underwent both resection of missed glands located in the neck or mediastinum and removal of the graft. En-bloc resection of autograft with surrounding muscle was required to avoid reoperation. When the intact PTH level dropped under 300 pg/ml, in the majority of patients renal HPT could be medically managed after the operation. The mean weight of the resected parathyroid tissue was 1583.7 mg. No specimen had histopathologically malignant features. Three patients suffered from hematoma in the wound. Graft-dependent recurrent renal HPT is not negligible. However, in the majority of patients, renal HPT can be controlled by removal of the autograft noninvasively. Total PTx with forearm autograft is preferable for hemodialysis patients, especially when long-term survival is expected.

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.

Parathyroid Hormone Venous Sampling Before Reoperative Surgery in Renal Hyperparathyroidism

To analyze the predictive values of selective venous sampling (SVS) in our own experience and in a systematic meta-analysis of the international literature and to compare them with the results of noninvasive localization studies before reoperative parathyroid surgery. Twenty-one consecutive patients with persistent or recurrent renal hyperparathyroidism underwent preoperative SVS and noninvasive imaging. These data were added to a systematic review of the literature on localization studies before reoperative surgery. The literature search included localization studies, recurrent hyperparathyroidism, and reoperation. STUDY SELECTION Prospective and retrospective studies that provided at least the true-positive rate of 1 procedure were included. Data from initial surgery, hyperfunctioning autografts, and case reports were excluded. Thirty-one publications reported on SVS (n = 22), technetium Tc 99m sestamibi scintigraphy (n = 17), thallium-technetium scintigraphy (n = 11), ultrasonography (n = 18), magnetic resonance imaging (n = 12), and computed tomography (n = 13). The overall analysis was performed by dividing the overall number of true- and false-positive results by the total number of patients. Localization by SVS was correct in 20 of 21 patients. In 1 patient with 2 localizations, only 1 was predicted correctly. Therefore, the sensitivity of SVS was at least 90%, with no false-positive results. Overall true- and false-positive rates, respectively, in 31 studies were 71% and 9% for SVS, 69% and 7% for technetium Tc 99m sestamibi scintigraphy, 54% and 16% for magnetic resonance imaging, 55% and 15% for thallium-technetium scintigraphy, 50% and 18% for ultrasonography, and 45% and 14% for computed tomography. With its high sensitivity, SVS is the gold standard in patients with persistent or recurrent renal hyperparathyroidism and negative results of noninvasive localization procedures. The noninvasive procedure of choice is now technetium Tc 99m sestamibi scintigraphy, with high sensitivity and a low rate of false-positive results.

Recurrent renal hyperparathyroidism and DNA analysis of autografted parathyroid tissue.

In spite of recent therapeutic advances, severe overt secondary hyperparathyroidism due to chronic renal failure necessitates parathyroidectomy and recurrent hyperparathyroidism is one of the most significant problems in this patient population. In the present study, the incidence of recurrent hyperparathyroidism was evaluated in relation to the histopathological features. Image cytometric DNA analysis was performed to estimate the proliferative potential of parathyroid tissue. The study comprised 248 patients who underwent parathyroidectomy from 1973 to 1991. The frequency of recurrent hyperparathyroidism after subtotal parathyroidectomy was 4 (21.1%) of 19 patients, the rate of graft-dependent recurrence after removal of residual parathyroid tissue with forearm autograft was 2 (50%) of 4 patients. The frequency of graft-dependent recurrence after total parathyroidectomy with forearm autograft was 16 (7.5%) of 212 patients. The frequency of recurrence was significantly higher (p less than 0.01) when nodular hyperplastic parathyroid tissue was autografted (17 of 68 patients, 25%) than when diffuse-hyperplastic tissue was grafted (1 of 105 patients, less than 1%). All 58 specimens subjected to image cytometric DNA analysis showed a diploid nuclear pattern cytometrically. However, the relative number of scattered cells that displayed cytometric nuclear DNA values outside the main diploid histogram peak was significantly greater (p less than 0.01) in nodular hyperplastic tissue before being autografted and in parathyroid tissue removed at re-operation performed for recurrence than in diffuse hyperplastic tissue. These clinical findings and results of DNA analysis clearly indicated that nodular hyperplastic parathyroid tissue has a higher growth potential, and it is concluded that to prevent graft-dependent recurrence, the nodular type of hyperplastic tissue should not be autografted.