Hyperkalemia Following Parathyroidectomy in Patients with Renal Hyperparathyroidism—New Thresholds for Urgent Perioperative Dialysis

Parathyroidectomy (PTX) is a mainstay of treating secondary hyperparathyroidism (SHPT) in patients with kidney failure in order to reduce the incidence of cardiovascular events (CVE), increase overall survival and improve quality of life. Perioperative hyperkalemia may lead to devastating cardiac complications. Distinct preoperative thresholds for serum potassium levels (SPL) were defined, but neither their usefulness nor consecutive risks are understood. This study compared the results and efficacy of different clinical procedures in preventing or treating perioperative hyperkalemia, including postoperative urgent hemodialysis (UHD). Methods: Patients from Charité-Universitätsmedizin Berlin and Rheinland Klinikum Lukaskrankenhaus, Neuss, undergoing PTX due to SHPT between 2008 and 2018 were analyzed retrospectively with regard to demographic parameters, surgery specific conditions and perioperative laboratory results. Comparisons of patient values from both centers with focus on perioperative hyperkalemia and the need for UHD were performed. Results: A total of 251 patients undergoing PTX for SHPT were included (Neuss: n = 121 (48%); Berlin: n = 130 (52%)). Perioperative hyperkalemia (SPL ≥ 5.5 mmol/L) was noted in 134 patients (53%). UHD on the day of surgery was performed especially in patients with intraoperative hyperkalemia, in females (n = 40 (16%) vs. n = 27 (11%); p = 0.023), in obese patients (n = 27 (40%) vs. n = 50 (28%), p = 0.040) and more often in patients treated in Neuss (n = 42 (35%) vs. 25 (19%); p = 0.006). For patients treated in Neuss, the intraoperative hyperkalemia cut-off level above 5.75 mmol/L was the most predictive factor for UHD (n = 30 (71%) vs. n = 8 (10%); p < 0.001). Concerning secondary effects of hyperkalemia or UHD, no patient died within the postoperative period, and only three patients suffered from acute CVE, with SPL > 5.5 mmol/L measured in only one patient. Conclusion: Perioperative values could not predict postoperative hyperkalemia with the need for UHD. Previously defined cut-off levels for SPL should be reconsidered, especially for patients undergoing PTX. Early postoperative dialysis in patients with postoperative hyperkalemia can be performed with a low risk for complications and may be indicated for all patients with increased perioperative SPL.

Practice variation in the treatment of patients with renal hyperparathyroidism: a survey-based study in the Netherlands

Background Renal hyperparathyroidism is a disease entity that is complex and poorly understood. Although there are guidelines regarding how to manage this patient group, evidence is scarce. Therefore, this survey-based study aims to map the physicians’ attitude in terms of preference for management of renal hyperparathyroidism and the influence of patient and respondent factors. Methods A survey was sent to Dutch societies of nephrology, endocrinology, and surgeons with interest in endocrine surgery. The survey consisted of eight case vignettes of renal hyperparathyroidism patients who were on hemodialysis and suitable for kidney transplantation, and varied in one of three patient variables import for decision making: age (40 vs. 65 years), parathyroid hormone (40 vs. 90 pmol/L), and serum calcium level (2.25 vs. 2.8 mmol/L). For each case, respondents could choose between maintaining conservative treatment (active vitamin D metabolites), calcimimetics, or subtotal parathyroidectomy as their treatment of choice. Categorical multilevel logistic models were used to investigate the association of patient and respondent variables with treatment preference. The influence of patient variables was determined independently of each other and by means of logistic regression the probabilities of treatment choice were calculated. Results In total, 115 surveys were included in the analysis. In 6 out of 8 cases, less than two-thirds of respondents agreed on the most favoured treatment. Among patient characteristics, the main disincentive for respondents not to choose conservative therapy was an elevated serum calcium level (subtotal parathyroidectomy vs conservative OR 93.1, 95%-CI: 48.39–179.07 and calcimimetics vs conservative OR 31.2 95%-CI: 18.58–52.30). Additionally, the most significant treatment differences were found between medical specialties and the experience of the respondents, expressed as the amount of cases the physician was involved in during the past year. Conclusions Elevated serum calcium levels were widely recognized and the prime reason for respondents to abandon conservative treatment. However, considerable disagreement in treatment preferences remained throughout the cases, demonstrating the current literature available being inconclusive in guiding physicians. Therefore, a high-quality trial comparing subtotal parathyroidectomy to medical treatment is needed to determine optimal treatment.

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.