Secondary hyperparathyroidism: Predictors and relationship with vitamin D status, bone turnover markers and bone mineral density.

INTRODUCTION: Secondary hyperparathyroidism (SHPT) has adverse implications for bone health but is relatively understudied. In this study we examine the prevalence and determinants of SHPT and describe the relationship of SHPT with bone turnover markers and bone mineral density (BMD) in older Irish adults. METHOD: Eligible participants (n = 4139) were identified from the Trinity-Ulster-Department of Agriculture (TUDA) study, a cohort of Irish adults aged ≥60 years. Exclusion criteria included an estimated glomerular filtration rate (eGFR) <30 ml/min and serum calcium >2.5 mmol/l to remove hyperparathyroidism due to advanced chronic kidney disease (CKD) and primary hyperparathyroidism respectively. The relationship between SHPT and bone turnover markers and BMD (measured by densitometry) was examined in a subsample (n = 1488). Vitamin D deficiency was defined as 25-hydroxyvitamin D [25 (OH)D] <30 nmol/l. RESULTS: Participants had a mean age of 73.6 ± 7.9 years, 65.1 % were female and 19.4 % were found to be vitamin D deficient. The prevalence of SHPT decreased as vitamin D increased, from 30.6 % in those deficient to 9.8 % in those with 25(OH)D ≥ 50 nmol/l and increased with declining kidney function. In non­calcium supplement users, principal determinants of SHPT were vitamin D deficiency (OR 4.18, CI 3.05-5.73, p < 0.001), eGFR 30-44 ml/min (OR 3.69, CI 2.44-5.57, p < 0.001), loop diuretic use (OR 3.52, CI 2.59-4.79, p < 0.001) and to a lesser extent body mass index (p = 0.001), eGFR 45-59 ml/min (p < 0.001) and 25(OH)D level 30-49 nmol/l (p = 0.002). Similar findings were observed in calcium supplement users, though proton pump inhibitors were also associated with SHPT (OR 1.55, CI 1.08-2.22, p = 0.018) while vitamin D 30-49 nmol/l was not. In participants with SHPT versus those without, bone turnover markers were higher: bone alkaline phosphatase (p = 0.017) and tartrate-resistant acid phosphatase (p = 0.033), whilst there was lower BMD at the neck of femur (0.880 vs. 0.903 g/cm2, p = 0.033) and total hip (0.968 vs. 0.995 g/cm2, P = 0.017). DISCUSSION: The results show that up to one in six older Irish adults had SHPT and this was associated with lower BMD and higher concentrations of bone turnover markers. Both vitamin D deficiency and 25(OH)D level 30-49 nmol/l were important predictors of SHPT. Loop diuretics and PPIs may also increase the risk of SHPT, and their use may need to be carefully considered in this population. Further studies examining the potential impact of these factors on bone health in similar populations to our study sample are warranted.

Surgical treatment of secondary hyperparathyroidism in children with chronic kidney disease. Experience in 19 patients.

OBJECTIVES: Secondary hyperparathyroidism (sHPT) is an important contributor to bone disease and cardiovascular calcifications in children with chronic kidney disease (CKD). When conservative measures are ineffective, parathyroidectomy is indicated. The aim of our study was to evaluate the efficacy and safety of subtotal parathyroidectomy (sPTX) in pediatric and adolescent patients, and to provide a rationale for considering this aggressive treatment in CKD patients with uncontrolled sHPT. METHODS: We retrospectively analyzed the medical records of 19 pediatric CKD patients on dialysis with refractory sHPT who underwent sPTX at our institution between 2010 and 2020. All patients had clinical, radiological, and biochemical signs of renal osteodystrophy. RESULTS: One year after sPTX, parathyroid hormone (PTH) levels (median and interquartile range (IQR)) dropped from 2073 (1339-2484) to 164 (93-252) pg/mL (p=0.0001), alkaline phosphatase (ALP) levels from 1166 (764-2373) to 410 (126-421) IU/L (p=0.002), and the mean (±SDS) calcium-phosphate (Ca*P) product from 51±11 to 41±13 mg2/dL2 (p=0.07). Postoperatively, all patients presented with severe hungry bone syndrome (HBS) and required intravenous and oral calcium and calcitriol supplementation. None of them had other postoperative complication. Histological findings had a good correlation with preoperative parathyroid ultrasound imaging (n: 15) in 100 % and with technetium-99m (99mTc) sestamibi scintigraphy (n: 15) in 86.6 %. Clinical and radiological signs of bone disease improved in all patients. CONCLUSIONS: Pediatric sPTX is effective and safe to control sHPT and calcium-phosphate metabolism in children with CKD on dialysis and may mitigate irreversible bone deformities and progression of cardiovascular disease.

Hypomagnesemia: a potential underlooked cause of persistent vitamin D deficiency in chronic kidney disease.

Magnesium and vitamin D play important roles in most cells of the body. These nutrients act in a coordinated fashion to maintain physiologic functions of various organs, and their abnormal balance could adversely affect these functions. Therefore, deficient states of both nutrients may lead to several chronic medical conditions and increased cardiovascular and all-cause mortality. Chronic kidney disease (CKD) patients have altered metabolism of both magnesium and vitamin D. Some studies indicate that magnesium could have a role in the synthesis and metabolism of vitamin D, and that magnesium supplementation substantially reversed the resistance to vitamin D treatment in some clinical situations. Recent observational studies also found that magnesium intake significantly interacted with vitamin D status and, particularly with the risk of cardiovascular mortality. It is therefore essential to ensure adequate levels of magnesium to obtain the optimal benefits of vitamin D supplementation in CKD patients. In this review, we discuss magnesium physiology, magnesium and vitamin D metabolism in CKD, potential metabolic interactions between magnesium and vitamin D and its clinical relevance, as well as the possible role of magnesium supplementation to assure adequate vitamin D levels.

Evaluation of Therapies for Secondary Hyperparathyroidism Associated with Vitamin D Insufficiency in Chronic Kidney Disease.

Introduction: Parathyroid hormone-lowering responses after administration of three different therapies capable of raising serum total 25-hydroxyvitamin D (25OHD) were evaluated in patients with secondary hyperparathyroidism (SHPT), vitamin D insufficiency (VDI), and stage 3 or 4 chronic kidney disease (CKD). Methods: Sixty-nine adult subjects with intact parathyroid hormone (iPTH) ≥85 and <500 pg/mL and VDI (25OHD <30 ng/mL) were randomized after ≥4-week washout to 2 months of open-label treatment with: (1) extended-release calcifediol (ERC) 60 µg/day; (2) immediate-release calcifediol (IRC) 266 µg/month; (3) high-dose cholecalciferol (HDC) 300,000 IU/month; or (4) paricalcitol plus low-dose cholecalciferol (PLDC) 1 or 2 µg and 800 IU/day, used as reference hormone replacement therapy. Serum 25OHD, calcium (Ca), phosphorus (P), plasma iPTH, and adverse events were monitored weekly. No clinically significant differences were observed at baseline between treatment groups. Results: Sixty-two subjects completed the study per protocol (PP; 14-17 per group). Mean (SD) 25OHD and iPTH at baseline were 20.6 (6.6) ng/mL and 144.8 (90) pg/mL, respectively. Mean 25OHD increased at end of treatment (EOT) to 82.9 (17.0) ng/mL with ERC (p < 0.001) and 30.8 (11.6) ng/mL with HDC (p < 0.05), but remained unchanged with IRC and PLDC. EOT 25OHD levels reached ≥30 ng/mL in all subjects treated with ERC and in 44% with HDC. All subjects attained EOT 25OHD levels ≥50 ng/mL with ERC versus none with other therapies. iPTH response rates at EOT (≥10, 20 or 30% below baseline) were similar for ERC and PLDC; rates for IRC and HDC were much lower. No significant changes from baseline were observed in ionized or corrected total Ca or P in any group. One episode of hypercalcemia (>10.3 mg/dL) occurred with PLDC. Hyperphosphatemia (>5.5 mg/dL) occurred once with ERC, eight times with HDC, 3 times with IRC, and twice with PLDC. Conclusion: ERC was highly effective in both raising serum 25OHD and decreasing iPTH in patients with SHPT, VDI, and stage 3 or 4 CKD. iPTH-lowering response rates with ERC were similar to daily PLDC, the reference therapy; rates with IRC or HDC were significantly lower. ERC is an attractive alternative to vitamin D hormone therapy in CKD patients.

A New Calculation Model for Calcium Requirements After Parathyroidectomy in Patients With Secondary Hyperparathyroidism.

OBJECTIVES: We aimed to develop a new calculation model for calcium requirements in dialysis patients following parathyroidectomy. METHODS: A total of 98 patients with secondary hyperparathyroidism receiving parathyroidectomy from January 2014 to January 2022 were enrolled in this study. Among these patients, 78 were randomly selected for construction of the calcium requirement calculation model, and the remaining 20 patients were selected for model validation. The calcium requirement model estimated the total calcium supplementation for 1 week after surgery using variables with significant relationships in the derivation group by stepwise multiple linear regression analysis. Bias, precision, and accuracy were measured in the validation group to determine the performance of the model. RESULTS: The model was as follows: calcium requirement for 1 week after surgery=33.798-8.929×immediate postoperative calcium+0.190×C-reactive protein-0.125×age+0.002×preoperative intact parathyroid hormone+0.003×preoperative alkaline phosphatase (R2=0.8). The model was successfully validated. CONCLUSION: We generated a novel model to guide calcium supplementation. This model can assist in stabilizing the serum calcium levels of patients during the early postoperative period. Furthermore, it contributes to the individualized and precise treatment of hypocalcemia in patients following parathyroidectomy.

Prevalence and risk factors for secondary hyperparathyroidism (SHPT) in patients undergoing bariatric surgery.

INTRODUCTION: Secondary hyperparathyroidism (SHPT) after bariatric surgery has significant adverse implications for bone metabolism, increasing the risk for osteoporosis and fracture. Our aim was to characterize prevalence and identify risk factors for SHPT in bariatric surgery patients. METHODS: We performed a single-institution, retrospective chart review of patients who underwent bariatric surgery from June 2017 through December 2021. Demographic and clinical data were collected, including serum parathyroid hormone, calcium, and vitamin D3 at enrollment and 3, 6, and 12-months postoperatively. Chi-square or Fisher's exact tests were used to analyze categorical data and Mann-Whitney U test for continuous data. Multivariable analysis using binomial logistic regression assessed risk factors for SHPT. P-values ≤ 0.05 were considered significant. RESULTS: 350 patients were analyzed. SHPT prevalence at any time point was 72.9%. 65.8% had SHPT at enrollment; 45.9% resolved with intensive vitamin supplementation; and 19.7% had recurrent SHPT. New-onset SHPT occurred in 8.6%. Persistent SHPT was present in 42.4% at 1-year. Baseline SHPT correlated with black race and T2DM. SHPT at any time point correlated with T2DM and higher baseline BMI. 1-year SHPT correlated with RYGB, depression, and longer time in program. SHPT was not correlated with %TBWL at any time point. In patients with SHPT, vitamin D3 deficiency prevalence was significantly higher at baseline (77.0%) compared to all post-bariatric time points (16.7%, 17.3%, and 23.1%; P < 0.0001). CONCLUSIONS: SHPT is highly prevalent in patients with obesity seeking weight loss surgery. 42% had persistent SHPT at 1-year despite appropriate vitamin supplementation. Current vitamin D3 and calcium supplementation protocols may not effectively prevent SHPT in many post-bariatric patients. Low prevalence of concomitant vitamin D3 deficiency with SHPT after bariatric surgery suggests that there may be alternative mechanisms in this population. Further studies are needed to develop effective treatment strategies to mitigate the adverse effects of bariatric surgery on bone metabolism.

Complications after radiofrequency ablation of hyperparathyroidism secondary to chronic kidney disease.

OBJECTIVE: To study the complications of ultrasound-guided radiofrequency ablation (RFA) in chronic kidney disease (CKD) patients undergoing renal replacement therapy with secondary hyperparathyroidism (SHPT). METHODS: This retrospective study reviewed the clinical data, including general information, examination results, treatment times, time interval, and postoperative complications, of 103 SHPT patients who received ultrasound-guided RFA treatment from July 2017 to January 2021. RESULTS: Of 103 patients, 52 required two sessions of RFA within a month. The incidence of recurrent laryngeal nerve injury at the second treatment was significantly higher than that at the first treatment (first session vs. second session, 5.77% vs. 21.15%; p = .021). Of all the enrolled 103 patients, 27 suffered complications after the first session of RFA. When we separated patients into complications group and non-complication group, we detected more ablated nodules in the complications group (Z = -2.222; p = .0026). Subgroup analysis further showed that the patients in the severe hypocalcemia group were younger (p = .005), had more ablated nodules (p = .003) and higher blood phosphorus (p = .012) and alkaline phosphatase (ALP) levels (p = .002). Univariate analysis showed that age, serum phosphorus, ALP, and number of ablated nodules were associated with a higher risk of severe hypocalcemia after the first session of RFA. CONCLUSIONS: An interval of more than 1 month between two treatments may help to avoid recurrent laryngeal nerve injury. Age, serum phosphorus, ALP, and number of ablated nodules were associated with a higher risk of severe hypocalcemia after the first session of RFA.

The effects and safety of high dose vitamin D3 in hemodialysis patients.

Background: Different studies have shown that hemodialysis patients require higher doses of Vitamin D3 (VD3) than the general population to achieve satisfactory replenishment. This study aims to assess the safety of such practice and its benefits on some of the parameters of Chronic Kidney Disease- Mineral and Bone Disorder (CKD-MBD). Methods: A single-center clinical trial assessing the benefits of high dose VD3 in hemodialysis patients. The dose of VD3 (300,000 IU) was administered orally and monthly from April to December 2020 (9 months) at the dialysis unit. The data analyzed were blood levels of calcium, phosphorus, alkaline phosphatase, 25(OH)D, 1,25(OH)2D and intact parathyroid hormone (iPTH) done every three months. Results: We could recruit a cohort of 23 patients. Blood levels of 25(OH)D increased significantly in 82.6% of the patients to above 30 ng/ml. A similar effect was observed with 1, 25(OH)2D levels. iPTH levels decreased significantly when levels of 25(OH)D exceeded 30ng/ml at the end of the nine months. Vitamin D serum levels were typically measured immediately before the next monthly dose was administered. Blood levels of calcium, phosphorus, and alkaline phosphatase were stable during the study period. No events of hypercalcemia were reported, and no patient discontinued the monthly VD3 supplementation. Conclusion: Monthly administration of a high dose of VD3 over a long period of nine months in hemodialysis patients was found to be safe and beneficial in VD3 replenishment. It also allowed a significant decrease in iPTH levels. Further studies are warranted to identify the therapeutic target level of 25(OH)D in hemodialysis patients, allowing beneficial effects on iPTH.

Vitamin D and Chronic Kidney Disease Association with Mineral and Bone Disorder: An Appraisal of Tangled Guidelines.

Chronic kidney disease (CKD) is a highly prevalent condition worldwide in which the kidneys lose many abilities, such as the regulation of vitamin D (VD) metabolism. Moreover, people with CKD are at a higher risk of multifactorial VD deficiency, which has been extensively associated with poor outcomes, including bone disease, cardiovascular disease, and higher mortality. Evidence is abundant in terms of the association of negative outcomes with low levels of VD, but recent studies have lowered previous high expectations regarding the beneficial effects of VD supplementation in the general population. Although controversies still exist, the diagnosis and treatment of VD have not been excluded from nephrology guidelines, and much data still supports VD supplementation in CKD patients. In this narrative review, we briefly summarize evolving controversies and useful clinical approaches, underscoring that the adverse effects of VD derivatives must be balanced against the need for effective prevention of progressive and severe secondary hyperparathyroidism. Guidelines vary, but there seems to be general agreement that VD deficiency should be avoided in CKD patients, and it is likely that one should not wait until severe SHPT is present before cautiously starting VD derivatives. Furthermore, it is emphasized that the goal should not be the complete normalization of parathyroid hormone (PTH) levels. New developments may help us to better define optimal VD and PTH at different CKD stages, but large trials are still needed to confirm that VD and precise control of these and other CKD-MBD biomarkers are unequivocally related to improved hard outcomes in this population.

RPS15A Mediates PI3K/AKT Signaling-Induced Parathyroid Cell Proliferation in Rats with Secondary Hyperparathyroidism.

OBJECTIVE: Ribosomal protein S15A (RPS15A) has been identified as a new oncogene in several tumors, but its functional role in secondary hyperparathyroidism (SHPT) characterized by increased serum parathyroid hormone (PTH) level and parathyroid cell proliferation remains unclear. METHODS: A rat model of SHPT was successfully established with a high-phosphorus diet plus 5/6 nephrectomy. ELISA assay was used to determine PTH, calcium and phosphorus and ALP activity. Cell proliferation was analyzed by Cell counting Kit-8 (CCK-8) assay. Flow cytometry assay was utilized to determine cell cycle distribution and apoptosis in parathyroid cells. LY294002, an inhibitor of PI3K/AKT signaling, was used to elucidate the relationship between RPS15A and PI3K/AKT signaling. Immunohistochemical (IHC) staining, quantitative real time PCR and western blot analysis were applied to determine related molecular levels. RESULTS: Our data showed an upregulation of RPS15A and activated PI3K/AKT signaling pathway in the parathyroid gland tissues of SHPT rats, accompanied with increased PTH, calcium and phosphorus levels. Knockdown of RPS15A decreased parathyroid cell proliferation, induced cell cycle arrest and apoptosis. Treatment with LY294002 reversed the effects of pcDNA3.1-RPSH15A in parathyroid cells. CONCLUSIONS: Our study demonstrated RPS15A-mediated PI3K/AKT pathway as a novel molecular mechanism in the pathogenesis of SHPT, which may provide a new drug target in the future.

Risk factors of recurrent secondary hyperparathyroidism after adequate primary surgical treatment.

Background: Secondary hyperparathyroidism (SHPT) is a common condition in patients with end-stage renal disease (ESRD) who are on dialysis. Parathyroidectomy is a treatment for patients when medical therapy has failed. Recurrence may occur and is indicated for further surgery in the era of improved quality of care for ESRD patients. Methods: We identified, 1060 patients undergoing parathyroidectomy from January, 2011 to June, 2020. After excluding patients without regular check-up at our institute, primary hyperparathyroidism, or malignancy, 504 patients were enrolled. Sixty-two patients (12.3%, 62/504) were then excluded due to persistent SHPT even after the first parathyroidectomy. We aimed to identify risk factors for recurrent SHPT after the first surgery. Results: During the study period, 20% of patients who underwent parathyroidectomy at our institute (in, 2019) was due to recurrence after a previous parathyroidectomy. There were 442 patients eligible for analysis of recurrence after excluding patients with the persistent disease (n = 62). While 44 patients (9.95%) had recurrence, 398 patients did not. Significant risk factors for recurrent SHPT within 5 years after the first parathyroidectomy, including dialysis start time to first operation time < 3 years (p = 0.046), postoperative PTH >106.5 pg/mL (p < 0.001), and postoperative phosphorus> 5.9 mg/dL (p = 0.016), were identified by multivariate analysis. Conclusions: The starting time of dialysis to first operation time < 3 years in the patients with dialysis, postoperative PTH> 106.5 pg/mL, and postoperative phosphorus> 5.9 mg/dL tended to have a higher risk for recurrent SHPT within 5 years after primary treatment.

Upacicalcet, a positive allosteric modulator of the calcium-sensing receptor, prevents vascular calcification and bone disorder in a rat adenine-induced secondary hyperparathyroidism model.

Secondary hyperparathyroidism (SHPT) is a major comorbidity of chronic kidney disease (CKD). Chronic elevation of PTH levels is associated with cortical bone deterioration and increase in the risk of fractures in CKD patients. Here, we evaluated the effect of repeated administration of upacicalcet, a novel positive allosteric modulator of the calcium-sensing receptor, in a rat model of adenine-induced renal failure, by determining serum levels of intact PTH (iPTH), calcium, phosphorus, creatinine, and urea nitrogen. Furthermore, parathyroid hyperplasia (parathyroid gland weight and Ki-67-positive cell density), ectopic calcification (calcium content in the thoracic aorta, kidney and heart and positive von Kossa staining in the thoracic aorta), and bone morphometry parameters (cortical porosity and fibrosis volume) were evaluated. Rats treated with either 0.2 mg/kg or 1 mg/kg upacicalcet exhibited significantly lower serum iPTH levels than CKD-control rats, as early as 7 days after the first dose. Repeated administration of upacicalcet reduced serum iPTH levels and inhibited parathyroid hyperplasia in rats with adenine-induced severe renal failure. Moreover, it suppressed ectopic calcification and cortical pore formation. In contrast, serum calcium and phosphorus levels were not significantly affected, suggesting a low risk of hypocalcemia, which often occurs with SHPT treatment. In conclusion, repeated administration of upacicalcet decreased serum iPTH levels and suppressed parathyroid hyperplasia in the adenine-induced CKD rat model of SHPT. Furthermore, ectopic calcification and cortical pore formation were suppressed without significant changes in blood mineral parameters. Upacicalcet safely inhibited the progression of SHPT in an adenine-induced CKD rat model.

Hyperparathyroidism in a Large Cohort of Chinese Patients With Tumor-induced Osteomalacia.

CONTEXT: Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome caused by excessive production of fibroblast growth factor 23 (FGF23) by a tumor. Hyperparathyroidism (HPT) including secondary HPT (SHPT) and tertiary HPT (THPT) in TIO patients, which is believed to be associated with phosphate supplementation, has not been well documented. OBJECTIVES: To clarify the prevalence, clinical characteristics, and risk factors for HPT in a large cohort of Chinese patients with TIO in our hospital. DESIGN, SETTING, AND PARTICIPANTS: This retrospective study enrolled 202 patients with TIO. MAIN OUTCOME MEASUREMENTS: Occurrence of HPT in patients with TIO. RESULTS: HPT was observed in 91 patients (91/202, 45.1%): 84 patients (41.6%) with SHPT and 7 patients (3.5%) with THPT. All patients with THPT underwent parathyroidectomy and only 1 patient experienced recurrence. Compared with patients without HPT, patients with SHPT had longer disease duration, higher rate of phosphate and calcitriol supplementation, lower serum calcium, lower urine calcium excretion, and higher urine phosphate excretion. Compared with patients with SHPT, patients with THPT had even longer disease duration and a higher rate of phosphate and calcitriol supplementation. PTH levels showed positive correlation with intact FGF23 and 1,25-dihydroxyvitamin D levels, but not 25-hydroxy vitamin D level in patients with TIO. Multivariate logistic regression analysis showed that long disease duration and phosphate supplementation were independently associated with occurrence of HPT in patients with TIO. Further logistic regression analysis and restricted cubic spline model revealed dose-response relationship between cumulative dose of phosphate supplementation and PTH levels. CONCLUSIONS: HPT is common in patients with TIO. To avoid the occurrence of HPT in patients with TIO, timely diagnosis and tumor resection is necessary and an excessive dose of phosphate supplementation is not suggested before surgery.

Effect of total parathyroidectomy in patients with secondary hyperparathyroidism: a retrospective study.

PURPOSE: To investigate the therapeutic efficacy, feasibility, and safety of total parathyroidectomy (tPTX) in the treatment of secondary hyperparathyroidism (SHPT). METHODS: The clinical data of 34 SHPT patients admitted to the Department of Nephrology, Yuxi People's Hospital, from January 2018 to January 2021 who had received tPTX, were retrospectively analyzed. The indications for tPTX were severe SHPT that did not respond to medical treatment and was ineligible for kidney transplantation. tPTX without autotransplantation was adopted to compare the level of symptom relief and changes in serum intact parathyroid hormone (iPTH), blood calcium, and blood phosphorus pre- and postoperatively. RESULTS: In 34 patients, 142 parathyroid glands were removed, including 21 ectopic parathyroid glands (14.78%). Six patients (17.64%, 6/34) had supernumerary parathyroid glands. At 6 h postoperatively, arthralgia and bone pain were significantly reduced to almost zero in 94.12% (32/34) of patients. At 24 h postoperatively, relief of bone pain and improvement of limb movement were observed in 100% (34/34) of patients, and pruritus almost disappeared in 86.36% (19/22) of patients. There were significant differences in iPTH (χ2 = 134.93, P < 0.05), calcium (χ2 = 23.02, P < 0.05), and phosphorus (χ2 = 102.11, P < 0.05) levels preoperatively and 40 min, 24 h, 1 week, half a year, and last available (> 1 year) postoperatively. The patients were followed up for 15-47 months (median 33 months). Hypoparathyroidism was observed in three patients, who underwent neck dissection or partial thymotomy concurrently for different reasons. No intractable hypocalcemia or adynamic bone disease occurred during the follow-up period. CONCLUSION: In SHPT patients who were ineligible for renal transplantation, tPTX was effective, safe, and reliable, with a low recurrence rate. However, when tPTX was performed alone without autologous transplantation, bilateral neck exploration was sufficient, and central neck dissection and thymic resection were inadvisable.

Efficacy of calcitriol combined with calcium receptor agonists in the treatment of chronic renal failure secondary hyperparathyroidism and its effect on serum β2-MG and FGF-23 / 中华内分泌外科杂志

Objective:To observe the efficacy of calcitriol combined with calcium receptor agonist therapy in patients with chronic renal failure-secondary hyperparathyroidism (CRF-SHPT) and its serum β2-Effects of β2-microglobulin ( β2-MG) and fibroblast growth factor-23 (FGF-23) levels. Methods:A total of 86 patients with CRF-SHPT who were admitted to the Department of Nephrology, Huzhou Hospital of Traditional Chinese Medicine, Zhejiang University of Traditional Chinese Medicine from Mar. 2020 to Mar. 2022 were included. Triol treatment) , combined treatment group (43 cases, calcitriol + calcium receptor agonist treatment) , the treatment effect was evaluated, and the serum phosphorus (P 3-) , serum calcium (Ca 2+) , ,and serum levels were measured before and after treatment intact parathyroid hormone (iPTH) , β2-MG, FGF-23 and renal function, blood lipid index levels, the occurrence of adverse reactions during the administration period, the measurement data were compared between groups using independent samples t test, count Comparison of data between groups was performed using the χ2 test. Results:The total effective rate (90.70%) in the combined treatment group was significantly higher than that in the control group (72.09%) ( χ2=4.91, P=0.027) ; the levels of P 3- and iPTH in the combined treatment group after treatment [ (220.16±23.76) ng/L, (1.22±0.14) mmol/L] were significantly lower than the control group [ (301.25±31.71) ng/L, (1.64±0.18) mmol/L], and the Ca 2+ level in the combined treatment group was significantly higher (2.59±0.41) mmol/L. Compared with the control group (2.26±0.34) mmol/L ( t=13.42, 12.08, 4.06, P=0.000, 0.000, 0.0000) , the serum levels of β2-MG and FGF-23 in the combined treatment group after treatment [ (34.67±4.12) mg/L, (71.36±8.05) ng/L] were significantly lower than the control group [ (40.36±4.87) mg/L, (78.97±8.73) ng/L] ( t=5.85, 4.20, P=0.000, 0.000) ; After treatment, the levels of triglyceride (TG) and total cholesterol (TC) in the combined treatment group [ (1.51±0.19) mmol/L, (4.11±0.51) mmol/L] were significantly lower than those in the control group[ (1.74±0.24) mmol/L, (4.75±0.59) mmol/L] ( t=4.93, 5.38, P=0.000, 0.000) ; Serum creatinine (Scr) , blood urea nitrogen (blood urea) in the two groups after treatment. There was no significant change in nitrogen) levels ( P>0.05) ; there was no significant difference in the incidence of adverse reactions between the combined treatment group and the control group during the treatment period ( P>0.05) . Conclusion:The treatment of CRF-SHPT patients with calcitriol combined with calcium receptor agonists can effectively reduce the iPTH level, improve the calcium-phosphorus imbalance and lipid metabolism disorder, and down-regulate the serum FGF-23 and β2-MG levels without damaging renal function of the residual of the patients.

[Reoperation treatment of persistent postoperative secondary hyperparathyroidism].

Objective:To evaluate the clinical effect of reoperation in persistent hyperparathyroidism （PHPT） patients after operation of parathyroidectomy combined with autotransplantation（PTX+AT） on secondary hyperparathyroidism （SHPT） . Methods:18 PHPT patients who treated with reoperation after PTX+AT were enrolled in this study during the period from Aug 2012 to Dec 2021 in the Department of Otolaryngology Head and Neck Surgery of Peking University Civil Aviation School of Clinical Medicine, Civil Aviation General Hospital. The remaining parathyroid glands were located by preoperative colour Doppler ultrasonography, radionuclide imaging, enhanced CT and MR imaging in the neck region . Based on the imaging findings, the remaining parathyroid glands were removed in situ, and the missed ectopic or extra parathyroid glands were resected with an extended surgical scope according to the parathyroid dissection method. The surgical effect was evaluated by the changes of clinical symptoms, the dynamic change of serum intact paramyroidhomone（i-PTH） between preoperative and postoperative periods and the surgical complications. Results:All the 18 patients accepted successful operation. 30 parathyroid glands were resected confirmed by postoperative pathology, including 16 in situ and 14 ectopic glands（5 in superior mediastinum, 4 in thymus, 2 in posterior mediastinum ,2 in thyroid glands, 1 in carotid sheath）.Osteoarthropathy and skin itching were significantly relieved or even disappeared at 6 h after surgery. The levels of serum i-PTH, calcium and phosphorus reached the standards and muscle weakness was significantly improved 1 week after surgery. 16 patients presented hypocalcemia and returned to normal after supplement of calcium. Hoarseness due to temporary injury of laryngeal nerve was found in 6 cases. No serious complications or death occurred after the operation.There was no recurrence after 1 year follow-up. Conclusion:Reoperation is the first choice for SHPT patients complicated with persistent hyperparathyroidism. Multiple imaging examinations are used to locate the residual parathyroid, especially the ectopic gland. Expanded surgical scope is applied to resect all the residual parathyroid glands（ectopic, in situ and concealed parathyroid） according to the concept of dissection parathyroidectomy. The surgery is effective and safe. Patients'quality of life and long-term survival rate is improved.

A Systematic Review and Meta-analysis of Efficacy and Safety of Calcimimetic Agents in the Treatment of Secondary Hyperparathyroidism in Patients with Chronic Kidney Disease.

BACKGROUND: Some reports have pointed out that calcimimetics agents are effective in the treatment of secondary hyperparathyroidism (SHPT) in chronic kidney disease (CKD) patients, but there is no detailed description of the advantages and disadvantages of calcimimetics agents of SHPT in CKD patients. We tried to pool the published data to verify the effectiveness of calcimimetics agents and to compare the advantages and disadvantages of cinacalcet compared with control in the treatment of SHPT in CKD patients. METHODS: We included eligible studies of published papers from January 1st, 2000 to December 31st, 2020 in Medline, Pubmed and Web of science databases, and the data were extracted for this meta-analysis. RESULTS: Twenty-seven studies were eligible, and all the included studies were randomized controlled trials (RCT) including patients treated with long-term dialysis. The results indicated that calcimimetic agents can reduce the parathyroid hormone (PTH, pg/ml) level (WMD = -178.22, 95% CI: -238.57, -117.86, P < 0.00001), calcium (Ca, mg/dl) level (WMD = -0.71, 95% CI: -0.86, -0.55, P < 0.00001), phosphorus (P, mg/dl) level (WMD = -0.32, 95% CI: -0.55, -0.08, P = 0.008), calcium-phosphorus product level (WMD = -7.73, 95% CI: -9.64, -5.82, P < 0.00001). Calcimimetic agents increased the bone alkaline phosphatase (BSAP, ng/ml) levels and rate of achieving target PTH, and reduced osteocalcin levels and the rate of parathyroidectomy. Calcimimetic agents increased the total adverse events' rate, the rate of hypocalcemia and gastrointestinal side effects (nausea, vomiting, abdominal pain and diarrhea), but there was no significant difference in serious adverse events between the calcimimetic agent group and control group. CONCLUSION: Calcimimetic agents can reduce the PTH level, Ca level, P level, calcium-phosphorus product level and do not increase serious adverse events.

Parathyroidectomy Improves the Consumption of Erythropoiesis-Stimulating Agents in Hemodialysis Patients.

Secondary hyperparathyroidism (SHPT) is common in end-stage renal disease (ESRD) patients, and it can suppress erythropoiesis. We aimed to investigate the relationship between the consumption of erythropoiesis-stimulating agents (ESAs) and parathyroidectomy (PTX) in ESRD patients with SHPT and to determine the predictors for anemia improvement. The current standard of chronic kidney disease anemia therapy relies on the prescription of iron supplementation, and ESA. We retrospectively analyzed 81 ESRD patients with PTX at Ditmanson Medical Foundation Chiayi Christian Hospital from July 2004 to Dec 2018. The requirement of ESA therapy markedly declined from a dose of 41.6 (interquartile range [IQR], 0−91.2) to 10.3 (IQR, 0−59.5, p = 0.001) unit/kg/week. In addition, 63.7% of patients required iron replacement therapy preoperatively and the proportion reduced to 52.5% after PTX (p < 0.001). The hemoglobin (Hb) level showed an insignificant change from a median value of 10.7 g/dL (9.5−11.6 g/dL) before PTX to 10.5 g/dL (9.6−11.2 g/dL) at 6 months after PTX. A preoperative Hb level ≤ 10 mg/dL (odds ratio [OR], 20.1; 95% confidence interval [CI], 4.71−125, p < 0.001) and transferrin saturation (TSAT) < 25% (OR, 12.8; 95% CI, 2.51−129, p < 0.001) were predictors for anemia improvement. Our study demonstrated that PTX markedly decreased the requirement of ESA. Patients with a low preoperative Hb level or low TSAT showed an increase in the Hb level after PTX. PTX may be considered not only for SHPT with refractory anemia but also for high ESA-dependent patients.

Semiquantitative assessment of 99mTc-MIBI uptake in parathyroids of secondary hyperparathyroidism patients with chronic renal failure.

Objective: To explore the valuably influential factors and improve the diagnostic accuracy and efficiency of 99mTc-methoxyisobutylisonitrile (MIBI) uptake in parathyroids of secondary hyperparathyroidism (SHPT) patients with chronic renal failure (CRF). Methods: The correlation analysis was performed between clinical indices related to CRF and 99mTc-MIBI uptake intensity TBR (the gray value mean ratio between the parathyroid target and the bilateral neck background, semiquantitatively calculated with ImageJ software). All clinical indices and TBRs were compared by a three- or two-level grouping method of MIBI uptake, which was visually qualitatively assessed. The three-level grouping method comprised slight, medium, and high groups with little, faint, and distinct MIBI concentration in parathyroids, respectively. The two-level grouping method comprised insignificant and significant groups with TBR greater than or less than 0.49-0.71, respectively. Results: MIBI uptake was significantly positively related to patient age, CRF course, hemodialysis vintage, serum parathyroid hormone (PTH), and alkaline phosphatase (AKP) but was significantly negatively related to serum uric acid (UA). MIBI washout was significantly positively related to patient age but was significantly negatively related to serum phosphorus (P) and calcium (Ca) × P. Oral administration of calcitriol and calcium could significantly reduce the MIBI uptake. MIBI uptake tendency might alter. Such seven indices, namely the MIBI uptake, CRF course, hemodialysis vintage, serum AKP, calcium, cysteine proteinase inhibitor C, and PTH, were comparable between the slight and medium groups but were significantly different between the slight and high groups or between the medium and high groups. The above seven indices plus blood urea nitrogen/creatinine were all significantly different between the insignificant and significant groups. All above significances were with P < 0.05. Conclusions: Patient age, CRF course, hemodialysis vintage, serum PTH, AKP, UA, phosphorus, Ca × P, oral administration of calcitriol and calcium, and parathyroids themselves can significantly influence MIBI uptake in parathyroids of SHPT patients with CRF. The two-level grouping method of MIBI intensity should be adopted to qualitatively diagnose the MIBI uptake.

Case report: Reoperative parathyroidectomy for large ectopic hyperplastic parathyroid in the mediastinum of a patient with recurrent secondary hyperparathyroidism.

Introduction: Secondary hyperparathyroidism (SHPT) is a common complication in hemodialysis patients with chronic renal failure uremia. For severe SHPT, parathyroidectomy is effective. Owing to the variability in parathyroid anatomy, surgical parathyroidectomy can be complex and many patients experience recurrent SHPT, which may require repeated surgery. These cases pose significant challenges to surgeons. Case description: An elderly woman with recurrent severe SHPT was admitted to our hospital. Preoperative methoxyisobutylisonitrile (MIBI) examination found a large ectopic parathyroid gland in the superior mediastinum, and she underwent reoperative parathyroidectomy. A large parathyroid gland in the right anterior mediastinum and another parathyroid gland in the left lingual lobe of the thymus were removed. The patient had postoperative hypocalcemia that was successfully corrected with calcium supplementation via femoral vein catheterization. During the 1-year postoperative follow-up, the patient's iPTH was well controlled and her blood calcium was within the normal range. Conclusion: We report a case of parathyroidectomy to remove multifocal ectopic hyperplastic parathyroid tissue in the mediastinum. Preoperative MIBI accurately detected the lesions. Calcium supplementation via femoral vein catheterization successfully corrected postoperative hypocalcemia. Postoperative follow-up for 1 year indicated that the surgery was successful.