Elevated parathyroid hormone one year after kidney transplantation is an independent risk factor for graft loss even without hypercalcemia.

BACKGROUND: Hypercalcemic hyperparathyroidism has been associated with poor outcomes after kidney transplantation (KTx). However, the clinical implications of normocalcemic hyperparathyroidism after KTx are unclear. This retrospective cohort study attempted to identify these implications. METHODS: Normocalcemic recipients who underwent KTx between 2000 and 2016 without a history of parathyroidectomy were included in the study. Those who lost their graft within 1 year posttransplant were excluded. Normocalcemia was defined as total serum calcium levels of 8.5-10.5 mg/dL, while hyperparathyroidism was defined as when intact parathyroid hormone levels exceeded 80 pg/mL. The patients were divided into two groups based on the presence of hyperparathyroidism 1 year after KTx. The primary outcome was the risk of graft loss. RESULTS: Among the 892 consecutive patients, 493 did not have hyperparathyroidism (HPT-free group), and 399 had normocalcemic hyperparathyroidism (NC-HPT group). Ninety-five patients lost their grafts. Death-censored graft survival after KTx was significantly lower in the NC-HPT group than in the HPT-free group (96.7% vs. 99.6% after 5 years, respectively, P < 0.001). Cox hazard analysis revealed that normocalcemic hyperparathyroidism was an independent risk factor for graft loss (P = 0.002; hazard ratio, 1.94; 95% confidence interval, 1.27-2.98). CONCLUSIONS: Normocalcemic hyperparathyroidism 1 year after KTx was an independent risk factor for death-censored graft loss. Early intervention of elevated parathyroid hormone levels may lead to better graft outcomes, even without overt hypercalcemia.

Predictors of Bone Mineral Density Improvement after Parathyroidectomy for Secondary Hyperparathyroidism: A Retrospective Single-Center Analysis.

BACKGROUND: Parathyroidectomy (PTx) reportedly increases bone mineral density (BMD) in patients with severe secondary hyperparathyroidism (SHPT). To date, however, there has not been sufficient evidence on predictors of BMD improvement post-PTx for SHPT, an issue the present retrospective cohort study aimed to address. METHODS: A total of 173 SHPT patients who underwent total PTx with forearm autograft between 2009 and 2017 were included in the present study. Demographic information, perioperative laboratory data and pre- and post-PTx BMD values (measured by dual-energy X-ray absorptiometry) were collected from their medical records. The change in BMD post-PTx in the lumbar spine was evaluated as the primary outcome. Then, a multivariate logistic regression analysis was performed for a ≥ 10% increase in BMD post-PTx. RESULTS: Overall, the median BMD in the lumbar spine was increased by 8.7% post-PTx. The multivariate logistic regression analysis revealed that age ≥ 70 years (P = 0.005; odds ratio [OR], 0.138; 95% confidence interval [CI]: 0.034-0.555), serum Ca level (P = 0.017; OR, 0.598; 95% CI: 0.392-0.911) and pre-PTx BMD in the lumbar spine (P = 0.003; OR, 0.013; 95% CI: 0.001-0.229) were negatively associated with a ≥ 10% increase in BMD post-PTx. CONCLUSION: Our study demonstrated that presurgical age, serum Ca levels and BMD values could better predict an improvement in BMD post-PTx in SHPT patients.

Comparison of Pre- and Post-transplant Parathyroidectomy in Renal Transplant Recipients and the Impact of Parathyroidectomy Timing on Calcium Metabolism and Renal Allograft Function: A Retrospective Single-Center Analysis.

BACKGROUND: The effect of parathyroidectomy (PTx) timing on serum calcium (Ca) levels and renal functions in renal transplant recipients with severe hyperparathyroidism (HPT) remains unclear. We retrospectively aimed to investigate and compare the clinical data of patients who underwent pre- and post-transplant PTx and elucidated the impact of PTx timing on serum Ca levels and renal graft outcomes after renal transplantation (RTx). METHODS: During January 2000-December 2016, 53 and 55 patients underwent post-transplant PTx (Post-RTx group) and pretransplant PTx (Pre-RTx group), respectively. The serum Ca levels and estimated glomerular filtration rate (eGFR) were assessed in both groups. RESULTS: At the end of the follow-up, the serum Ca levels were significantly higher and the incidence of hypocalcemia was significantly lower in the Pre-RTx group than in the Post-RTx group [9.5 vs. 8.9 mg/dL, P < 0.001; 14.5% vs. 34.0%, P = 0.024]. The decrease in the eGFR 12-36 months after RTx was more significant in the Post-RTx group than in the Pre-RTx group (-13.8% vs. -0.9%; P = 0.001). A logistic regression involving age, sex, dialysis period, and serum parathormone level revealed that post-transplant PTx is an independent risk factor for persistent hypocalcemia at the end of the follow-up (P = 0.034) and for a >20% decrease in the eGFR 12-36 months after RTx (P = 0.029). CONCLUSIONS: In renal transplant candidates with severe HPT, pretransplant PTx should be considered to prevent persistent hypocalcemia and deterioration of the renal graft function.

Development of Severe Hyperparathyroidism Despite Short-Term Renal Replacement Therapy.

BACKGROUND: We occasionally experience cases of severe secondary hyperparathyroidism (SHPT) that require parathyroidectomy (PTX) despite undergoing short-term renal replacement therapy (RRT). Because the characteristics of such cases have never been discussed, we aimed to elucidate the pathophysiology of severe SHPT after short-term RRT by retrospectively analyzing clinical data. METHODS: A total of 1013 patients with severe SHPT underwent PTX between January 2007 and April 2016 at Nagoya Daini Red Cross Hospital. Of these patients, 570 underwent RRT for ≥10 years (long RRT group) and 23 for ≤1 year (short RRT group). We retrospectively investigated and compared patient characteristics, preoperative data, subjective symptoms, and bone lesion incidence between the two groups. RESULTS: A higher proportion of subjects with congenital or hereditary diseases as primary disease for chronic kidney disease (CKD) (21.7% (5/23) vs. 6.3% (36/570); P = 0.016) and longer predialysis period (21.2 ± 14.0 vs. 10.1 ± 9.2 years; P < 0.001) were observed in the short RRT group than in the long RRT group. Furthermore, lower serum calcium and phosphate levels, heavier parathyroid glands, and severe bone lesions were observed in the short RRT group than in the long RRT group. CONCLUSION: Severe SHPT after short-term RRT appeared to occur because of long-term CKD before initiating RRT. Therefore, treating mineral and bone disorders during the early CKD stage might prevent severe SHPT development before initiating RRT.

Effect of Oral Alfacalcidol on Clinical Outcomes in Patients Without Secondary Hyperparathyroidism Receiving Maintenance Hemodialysis: The J-DAVID Randomized Clinical Trial.

Importance: Patients with chronic kidney disease have impaired vitamin D activation and elevated cardiovascular risk. Observational studies in patients treated with hemodialysis showed that the use of active vitamin D sterols was associated with lower risk of all-cause mortality, regardless of parathyroid hormone levels. Objective: To determine whether vitamin D receptor activators reduce cardiovascular events and mortality in patients without secondary hyperparathyroidism undergoing hemodialysis. Design, Setting, and Participants: Randomized, open-label, blinded end point multicenter study of 1289 patients in 207 dialysis centers in Japan. The study included 976 patients receiving maintenance hemodialysis with serum intact parathyroid hormone levels less than or equal to 180 pg/mL. The first and last participants were enrolled on August 18, 2008, and January 26, 2011, respectively. The final date of follow-up was April 4, 2015. Interventions: Treatment with 0.5 µg of oral alfacalcidol per day (intervention group; n = 495) vs treatment without vitamin D receptor activators (control group; n = 481). Main Outcomes and Measures: The primary outcome was a composite measure of fatal and nonfatal cardiovascular events, including myocardial infarctions, hospitalizations for congestive heart failure, stroke, aortic dissection/rupture, amputation of lower limb due to ischemia, and cardiac sudden death; coronary revascularization; and leg artery revascularization during 48 months of follow-up. The secondary outcome was all-cause death. Results: Among 976 patients who were randomized from 108 dialysis centers, 964 patients were included in the intention-to-treat analysis (median age, 65 years; 386 women [40.0%]), and 944 (97.9%) completed the trial. During follow-up (median, 4.0 years), the primary composite outcome of cardiovascular events occurred in 103 of 488 patients (21.1%) in the intervention group and 85 of 476 patients (17.9%) in the control group (absolute difference, 3.25% [95% CI, -1.75% to 8.24%]; hazard ratio, 1.25 [95% CI, 0.94-1.67]; P = .13). There was no significant difference in the secondary outcome of all-cause mortality between the groups (18.2% vs 16.8%, respectively; hazard ratio, 1.12 [95% CI, 0.83-1.52]; P = .46). Of the 488 participants in the intervention group, 199 (40.8%) experienced serious adverse events that were classified as cardiovascular, 64 (13.1%) experienced adverse events classified as infection, and 22 (4.5%) experienced malignancy-related serious adverse events. Of 476 participants in the control group, 191 (40.1%) experienced cardiovascular-related serious adverse events, 63 (13.2%) experienced infection-related serious adverse events, and 21 (4.4%) experienced malignancy-related adverse events. Conclusions and Relevance: Among patients without secondary hyperparathyroidism undergoing maintenance hemodialysis, oral alfacalcidol compared with usual care did not reduce the risk of a composite measure of select cardiovascular events. These findings do not support the use of vitamin D receptor activators for patients such as these. Trial Registration: UMIN-CTR Identifier: UMIN000001194.

Cinacalcet hydrochloride relieves hypercalcemia in Japanese patients with parathyroid cancer and intractable primary hyperparathyroidism.

Pharmacological treatment of hypercalcemia is essential for patients with parathyroid carcinoma and intractable primary hyperparathyroidism (PHPT). Use of the calcimimetic cinacalcet hydrochloride (cinacalcet) is an option to treat such patients. We investigated the efficacy and safety of cinacalcet in Japanese patients with parathyroid carcinoma and intractable PHPT. Five Japanese patients with parathyroid carcinoma and two with intractable PHPT were enrolled in an open-label, single-arm study consisting of titration and maintenance phases. Cinacalcet doses were titrated until the albumin-corrected serum calcium concentration decreased to 10.0 mg/dL or less or until dose escalation was considered not necessary or feasible. Serum calcium concentration at the baseline was 12.1 ± 1.3 mg/dL (mean ± standard deviation; range 10.4-14.6 mg/dL) and decreased to 10.1 ± 1.6 mg/dL (range 8.6-13.3 mg/dL) at the end of the titration phase with cinacalcet at a dosage of up to 75 mg three times a day. At the end of the titration phase, at least a 1 mg/dL reduction in serum calcium concentration from the baseline was observed in five patients (three with carcinoma and two with PHPT), and it decreased to the normocalcemic range in five patients (three with carcinoma and two with PHPT). Common adverse events were nausea and vomiting. One patient discontinued participation in the study because of an adverse event, liver disorder. Cinacalcet effectively relieved hypercalcemia in 60% of the Japanese patients with parathyroid carcinoma and might be effective in those with intractable PHPT. The drug might be tolerable and safe at a dosage of at most 75 mg three times a day.

Location Frequency of Missed Parathyroid Glands After Parathyroidectomy in Patients with Persistent or Recurrent Secondary Hyperparathyroidism.

BACKGROUND: Reoperative parathyroidectomy (RPTX) because parathyroid glands have been missed is frequently required in patients with secondary hyperparathyroidism (SHPT). The usual locations of these missed glands in patients with SHPT are yet to be fully elucidated. METHODS: We retrospectively investigated the locations of missed glands in 165 patients who underwent RPTX for persistent or recurrent SHPT at our institution from August 1982 to July 2014. At our institution, total parathyroidectomy with forearm autograft is the routine operative procedure for SHPT. We also routinely resect the thymic tongue. RESULTS: Of 165 patients, 82 underwent initial parathyroidectomy at our institution (Group A), and the remaining 83 underwent initial parathyroidectomy at other institutions (Group B). A total of 239 parathyroid glands were resected (Group A, 93; Group B, 146). Missed glands were most commonly located in the mediastinum (Group A, 22/93) and the thymic tongue (Group B, 31/146). CONCLUSIONS: In patients with persistent or recurrent SHPT, ectopic parathyroid glands are frequently located in the mediastinum and thymic tongue. Therefore, resecting the thymic tongue during the initial operation may reduce the need for RPTX.

Characteristics of Persistent Hyperparathyroidism After Renal Transplantation.

BACKGROUND: Persistent hyperparathyroidism (HPT) after renal transplantation (RTx), termed tertiary HPT (THPT), is not uncommon. However, risk factors and appropriate operative procedures for THPT are poorly understood. METHODS: A retrospective study of patients who underwent RTx without pre-transplant parathyroidectomy (PTx) was performed at our hospital between January 2001 and March 2011. Risk factors for the development of THPT were investigated by comparing THPT and non-THPT groups. We retrospectively analyzed patients with THPT who underwent total PTx with forearm autograft. Pre- and postoperative (1 year after PTx) laboratory results were analyzed for PTx efficacy. RESULTS: Data for 520 patients were analyzed. On multivariate analysis, long dialysis duration (p = 0.009, hazard ratio (HR) 1.01), large maximum parathyroid gland size before RTx (p = 0.003, HR 1.23), pre-RTx high intact parathyroid hormone (iPTH) (p = 0.041, HR 1.01), post-RTx (<2 weeks) high calcium (Ca) (p < 0.001, HR 25.04), and post-RTx high alkaline phosphatase (ALP) (p = 0.027, HR 0.99) were identified as risk factors for THPT. Patients who underwent PTx showed significant improvement compared with baseline for serum Ca, phosphorus, iPTH, and ALP. Serum creatinine showed no significant difference. CONCLUSIONS: Several risk factors for THPT development were identified. PTx for patients with THPT significantly improved serum Ca, iPTH, ALP, and phosphorous levels. There was no significant difference in renal function after PTx. Therefore, total PTx with forearm autograft may be an appropriate surgical approach for patients with THPT.

Death and kidney allograft dysfunction after bacteremia.

BACKGROUND: Some studies have reported causal associations between bacteremia and mortality or allograft loss in kidney transplant recipients (KTR). However, few studies have assessed the clinical course of kidney function and the risk of acute allograft rejection after bacteremia. METHODS: We retrospectively reviewed 902 kidney transplants performed at Nagoya Daini Red Cross Hospital between January 1, 2002 and March 31, 2014. Forty-five living donor kidney transplant recipients with single bacteremia were included. We analyzed death, change in kidney function, and development of acute allograft rejection 12 months after bacteremia according to the following groups: primary source of bacteremia (urinary tract or other sources), site of acquisition (community acquired or nosocomial), severity (not meeting the systemic inflammatory response syndrome criteria and sepsis or severe sepsis and septic shock), empiric antibiotic use (appropriate or inappropriate), and baseline kidney function (estimated glomerular filtration rate ≤44.7 or ≥44.8 ml/min). RESULTS: Urinary tract infection (UTI) was the leading cause of bacteremia (68.9 %), and Escherichia coli was the most common pathogen. Three cases (6.7 %) died of infection that caused bacteremia within 12 months. Pneumonia accounted for two-thirds. Kidney function declined 1 week after bacteremia (P < 0.05), particularly in severe cases. Thereafter, kidney function was comparable to baseline level in each group (P ≥ 0.05). Severe UTI was associated with subsequent acute allograft rejection (P = 0.03). CONCLUSIONS: Pneumonia in KTR should be managed with caution. Kidney function generally returned to baseline level after bacteremia. However, severe UTI may be associated with subsequent acute allograft rejection.

Beneficial effects of preemptive kidney transplantation on calcium and phosphorus disorders in early post-transplant recipients.

BACKGROUND: Recently, preemptive kidney transplantation (PKT) has increased in Japan; however, the effects of PKT on calcium (Ca) and phosphorus (Pi) metabolism are poorly understood. METHODS: Thirty-two consecutive patients were enrolled in this study at Nagoya Daini Red Cross Hospital. Fifteen patients were in the PKT group and 17 patients were in the non-PKT group. Parameters of Ca and Pi metabolism, including fibroblast growth factor (FGF) 23 and intact parathyroid hormone, were measured before transplantation and 1, 3, and 24 weeks after transplantation. RESULTS: FGF 23 decreased dramatically in both groups after transplantation; however, FGF 23 before transplantation and at 1 and 3 weeks after transplantation was significantly lower in the PKT group than in the non-PKT group (p < 0.05). Although iPTH levels were higher in the PKT group than in the non-PKT group before transplantation, these levels were lower in the PKT group at 24 weeks after transplantation (p < 0.05). Corrected Ca was lower at 24 weeks in the PKT group (p < 0.05), whereas Pi was lower in the non-PKT group at 1 and 3 weeks (p < 0.05), but not significantly different at 24 weeks. Multivariate linear regression analysis revealed that FGF 23 before transplantation was the strongest predictor of Ca and Pi disorders in early post-transplant recipients. CONCLUSIONS: This study suggests that PKT has beneficial effects on Ca and Pi metabolism and pre-transplant FGF 23 levels are a good marker of post-transplant Ca and Pi metabolism disorders.

How to estimate kidney function in kidney transplant recipients with mild to moderate kidney impairment: comparison of estimated glomerular filtration (eGFR) values between creatinine-based GFR equations and cystatin C-based GFR equations for Japanese population.

BACKGROUND: With the recent increase in renal transplantations in Japan, accurate assessment of renal function is required. METHODS: This study included 73 patients who had undergone renal transplantation at Nagoya Daini Red Cross Hospital at least 6 months previously and had stable renal function for >3 months. Glomerular filtration rates (GFRs) were measured by inulin clearance (mGFR) and compared with estimated cystatin C-based GFRs (eGFRcys), estimated creatinine-based GFRs (eGFRcre) and their average values (eGFRave). RESULTS: mGFR was 43.3 ± 14.1 mL/min/1.73 m(2), eGFRcre was 39.6 ± 11.7, eGFRcys was 56.0 ± 17.1, and eGFRave was 47.8 ± 13.7 mL/min/1.73 m(2). Serum cystatin C was 1.39 ± 0.37 mg/L and serum creatinine was 1.58 ± 0.51 mg/dL. The correlation coefficients between mGFR and eGFRcre, eGFRcys, and eGFRave were 0.768, 0.831, and 0.841, respectively (P < 0.001, for all).The intraclass correlation coefficients were 0.754, 0.816, and 0.840, respectively (P < 0.001, for all).The mean differences between measured and estimated GFR values were 3.74 mL/min/1.73 m(2) with a root-mean square error (RMSE) of 9.06 for eGFRcre, +12.64 with RMSE of 9.48 for eGFRcys, and +4.45 with RMSE of 7.86 for eGFRave. Bland-Altman plots showed that eGFRcys overestimated GFR values compared with mGFR values in most cases and that eGFRave overestimated GFR values in 53 of 73 cases, whereas eGFRcre underestimated the values in 53 of 73 cases. CONCLUSION: eGFRave may be the best marker to estimate kidney function in Japanese renal transplant recipients with mildly reduced or normal kidney function.

Hypocalcemia immediately after renal transplantation.

BACKGROUND: After renal transplantation (RTX), hypercalcemia, mainly due to persistent hyperparathyroidism, and hypophosphatemia, caused by the improved ability to excrete phosphorus in the renal tubules, are expected. However, immediately after RTX, a transient reduction in serum calcium (Ca) levels has been previously reported, the reason for which is not clear. PATIENTS AND METHODS: In 21 patients receiving ABO compatible living donor kidney transplants, serum levels of Ca, phosphorus, intact parathyroid hormone (iPTH), 1,25-dihydroxyvitamin D, and tacrolimus were measured within three wk after RTX, along with urinary Ca and phosphorus excretion. The immunosuppressive regimen consisted of a three-drug combination including a glucocorticoid, a calcineurin inhibitor, and an antimetabolite agent. RESULTS: Serum Ca levels declined significantly during the first post-operative week. Urinary Ca excretion increased immediately after RTX and gradually normalized. Increased urinary Ca excretion did not correlate with serum levels of iPTH and tacrolimus. CONCLUSIONS: Immediately after RTX, regardless of serum iPTH and tacrolimus levels, transient increases in urinary Ca excretion and hypocalcemia were observed. Administration of glucocorticoids is one potential cause of inappropriate urinary Ca wasting.

Treatment for secondary hyperparathyroidism focusing on parathyroidectomy.

Secondary hyperparathyroidism (SHPT) is a major problem for patients with chronic kidney disease and can cause many complications, including osteodystrophy, fractures, and cardiovascular diseases. Treatment for SHPT has changed radically with the advent of calcimimetics; however, parathyroidectomy (PTx) remains one of the most important treatments. For successful PTx, removing all parathyroid glands (PTGs) without complications is essential to prevent persistent or recurrent SHPT. Preoperative imaging studies for the localization of PTGs, such as ultrasonography, computed tomography, and 99mTc-Sestamibi scintigraphy, and intraoperative evaluation methods to confirm the removal of all PTGs, including, intraoperative intact parathyroid hormone monitoring and frozen section diagnosis, are useful. Functional and anatomical preservation of the recurrent laryngeal nerves can be confirmed via intraoperative nerve monitoring. Total or subtotal PTx with or without transcervical thymectomy and autotransplantation can also be performed. Appropriate operative methods for PTx should be selected according to the patients' need for kidney transplantation. In the case of persistent or recurrent SHPT after the initial PTx, localization of the causative PTGs with autotransplantation is challenging as causative PTGs can exist in the neck, mediastinum, or autotransplanted areas. Additionally, the efficacy and cost-effectiveness of calcimimetics and PTx are increasingly being discussed. In this review, medical and surgical treatments for SHPT are described.

Maximal parathyroid gland diameter as a predictive factor for autograft-dependent recurrent secondary hyperparathyroidism after total parathyroidectomy.

Introduction: Following total parathyroidectomy (PTx), transcervical thymectomy, and forearm autograft for secondary hyperparathyroidism (SHPT), recurrent SHPT can occur in the autografted forearm. However, few studies have investigated the factors contributing to re-PTx due to autograft-dependent recurrent SHPT before the completion of the initial PTx. Methods: A total of 770 patients who had autografted parathyroid fragments derived from only one of the resected parathyroid glands (PTGs) and who had undergone successful initial total PTx and transcervical thymectomy-defined by serum intact parathyroid hormone level < 60 pg/mL on postoperative day 1-between January 2001 and December 2022 were included in this retrospective cohort study. Factors contributing to re-PTx due to graft-dependent recurrent SHPT before the completion of the initial PTx were investigated using multivariate Cox regression analysis. Receiver operating characteristic (ROC) curve analysis was performed to obtain the optimal maximum diameter of PTG for autograft. Results: Univariate analysis showed that dialysis vintage and maximum diameter and weight of the PTG for autograft were significant factors contributing to graft-dependent recurrent SHPT. However, multivariate analysis revealed that dialysis vintage (P=0.010; hazard ratio [HR], 0.995; 95% confidence interval [CI], 0.992-0.999) and the maximum diameter of the PTG for autograft (P=0.046; HR, 1.107; 95% CI, 1.002-1.224) significantly contributed to graft-dependent recurrent SHPT. ROC curve analysis showed that < 14 mm was the optimal maximum diameter of PTG for autograft (area under the curve, 0.628; 95% CI, 0.551-0.705). Conclusions: The dialysis vintage and maximum diameter of PTG for autograft may contribute to re-PTx due to autograft-dependent recurrent SHPT, which can be prevented by using PTGs with a maximum diameter of < 14 mm for autograft.

[Kidney and bone update : the 5-year history and future of CKD-MBD. Parathyroidectomy for secondary hyperparathyroidism].

Induction of Cinacalcet HCl (cinacalcet) has influenced treatment of secondary hyperparathyroidism (SHPT) in Japan. The number of parathyroidectomy (PTx) for SHPT has remarkably decreased. Fundamentally patients with advanced SHPT refractory to medical treatment including cinacalcet should require PTx. PTx can release SHPT most dramatically. Because in Japan, many hemodialysis patients are expected for long-term survival, we should decide the indication of PTx concerning long-term treatment and economical aspect. We recommend PTx for patients who are expected for long term survival and SHPT is resistant to vitamin D activators, patients with severe symptoms of SHPT, patients with SHPT resistant to cinacalcet, patients with hypercalcemia and/or hyperphosphatemia resistant to medical treatment, and patients who cannot tolerate to side effect of cinacalcet. Some patients with advanced SHPT which is not controlled by surgical treatment should require cinacalcet therapy as rescuing treatment before operation.

Preservation of the nonrecurrent laryngeal nerve using intraoperative nerve monitoring during endoscopic thyroidectomy.

A 40-year-old woman underwent right lobe thyroidectomy for thyroid nodules that increased in size from 17 mm to 33.5 mm within 1 year. Identification of arteria lusoria using computed tomography suggested the presence of a right nonrecurrent laryngeal nerve (RNRLN). Endoscopic thyroidectomy was performed under general anesthesia. The right vagal nerve was first identified between the common carotid artery and jugular vein. A positive response was confirmed via intraoperative neuromonitoring (IONM), implying that the RNRLN did not branch from the central side of the stimulated point of the vagal nerve. The RNRLN was confirmed using IONM around the middle to lower pole of the right thyroid gland. The right thyroid lobe was successfully removed, with meticulous preservation of the RNRLN. The motion of the vocal cord, examined by an ear-nose-throat doctor postoperatively, was intact. We demonstrated the efficacy of IONM in patients with RNRLN who underwent endoscopic thyroidectomy.

Intraoperative intact parathyroid hormone monitoring and frozen section diagnosis are essential for successful parathyroidectomy in secondary hyperparathyroidism.

Background: Total parathyroidectomy (PTx) is often performed to treat secondary hyperparathyroidism (SHPT). Successful PTx is essential to prevent recurrent and persistent SHPT because remnant parathyroid glands (PTGs) in the neck can be stimulated and may secrete excessive parathyroid hormone (PTH) in end-stage renal disease. However, to date, few studies have investigated factors contributing to successful PTx before the completion of surgery. Materials and methods: Between August 2010 and February 2020, 344 patients underwent total PTx, transcervical thymectomy, and forearm autograft for SHPT at our institute. Factors contributing to successful PTx before the completion of surgery were investigated. Preoperative imaging diagnoses, including computed tomography, ultrasonography, technetium-99m methoxyisobutylisonitrile (99mTc-MIBI) scintigraphy, intraoperative intact PTH (IOIPTH) monitoring, and frozen section histologic diagnosis, were performed. Successful PTx was defined as intact PTH level < 60 pg/mL on postoperative day 1. A sufficient decrease in IOIPTH level was defined as > 70% decrease in intact PTH levels measured 10 min after total PTx and transcervical thymectomy compared to intact PTH levels measured before skin incision. Logistic regression analysis was conducted to investigate factors contributing to PTx success. Results: Univariate analysis showed that the number of all PTGs identified preoperatively by imaging modalities and the specimens submitted for frozen section diagnosis, which surgeon presumed to be PTGs, were not significant factors contributing to successful PTx. However, multivariate analysis revealed that the number of PTGs identified by frozen section diagnosis (P < 0.001, odds ratio [OR] 4.356, 95% confidence interval [CI] 2.499-7.592) and sufficient decrease in IOIPTH levels (P = 0.001, OR 7.847, 95% CI 2.443-25.204) significantly contributed to successful PTx. Conclusion: Sufficient intact PTH level decrease observed on IOIPTH monitoring and the number of PTGs identified by frozen section diagnosis contributed to successful PTx for SHPT. IOIPTH monitoring and frozen section diagnosis are essential for achieving successful PTx for SHPT.

Renal hyperparathyroidism.

The number of the patients with chronic kidney disease is now increasing in the world. The pathophysiology of renal hyperparathyroidism is closely associated with Klotho-FGF-endocrine axes, which must be solved definitively as early as possible. It was revealed that the expression of fgf23 is activated by calciprotein particles, which induces vascular ossification. And it is well known that phosphorus overload directly increases parathyroid hormone and hyperparathyroid bone disease develops in those subjects. On the other hand, low turnover bone disease is often recently. Both the patients with chronic kidney disease suffering from hyperparathyroid bone disease or low turnover bone disease are associated with increased fracture risk. Micropetrosis may be one of the causes of increased fracture risk in the subjects with low turnover bone disease. In this chapter, we now describe the diagnosis, pathophysiology and treatments of renal hyperparathyroidism.

Immunocytochemical analysis for differential diagnosis of thyroid lesions using liquid-based cytology.

Recently, liquid-based cytology (LBC) has been widely applied to various samples in diagnostic cytology and its usefulness has been reported. In this study, we investigated thyroid cytology that applied LBC and immunocytochemistry to achieve more objective diagnosis and greater diagnostic accuracy. This study included 125 cases (57 papillary carcinomas (PCs), 22 follicular tumors, 43 adenomatous goiters and 3 with Basedow's disease). After preparing the LBC slide, immunocytochemical staining was performed on each slide with six antibodies (HBME-1, cytokeratin 19 (CK19), high molecular weight cytokeratin (34JE12), galectin-3, CD15 and CA 19-9). All antibodies presented immunopositivity frequently in PCs, but only a few or some of them were positive in other cases. These antibodies were considered positive markers for PCs, and the most reliable marker was 34betaE12; its sensitivity, specificity and diagnostic accuracy were 82.5%, 100% and 92.0%, respectively. Relations of immunocytochemical profiles against these markers were assessed using panel 34betaE12, GAL-3 and CK19. More than or equal to two of these markers showed co-positive in 53 of 57 PCs, and negative for all markers was observed in only one case. In the other (non PC) cases, the former was 0 of 58 and the latter was 40 cases. In this panel, the sensitivity, specificity and diagnostic accuracy were 93.0%, 100% and 96.8%, respectively. All of these values were higher than or equal to single values of 34betaE12. We concluded that the panel in this study is useful for more objective and accurate diagnosis of thyroid cytology.

[Morphological analysis of bone dynamics and metabolic bone disease. A case report of recurrent renal hyperparathyroidism].

A 39-years-old chronic hemodialysis patient who developed recurrent hyperparathyroidism after total parathyroidectomy with immediate autotransplantation (PTX-AT) is now reported. The patient had undergone bilateral nephrectomy due to bilateral renal cell carcinoma at 4 and 5 years after the initiation of dialysis, followed by the treatment with interleukin-2 administration. Secondary hyperparathyroidism was treated by PTX-AT, followed by confirmation of reduced bone turnover. The parathyroid glands were huge and the total weight of the parathyroid glands was 14.3 gr. Pathological examination revealed nodular hyperplastic parathyroid tissue in all four glands. However, the serum intact parathyroid hormone (iPTH) increased again at 7 years after the PTX, and bone biopsy revealed high turnover bone disease. The recurrent hyperparathyroidism was treated with cinacalcet hydrochloride to reduce the serum iPTH level.