Impact of Parathyroidectomy Versus Oral Cinacalcet on Bone Mineral Density in Patients on Peritoneal Dialysis With Advanced Secondary Hyperparathyroidism: The PROCEED Pilot Randomized Trial.

RATIONALE & OBJECTIVE: Parathyroidectomy and calcimimetics have been used to reduce fracture risk in patients with kidney failure and advanced secondary hyperparathyroidism (SHPT), but direct comparisons of these treatment approaches have not been implemented. This pilot study compared their effects on bone mineral density (BMD) in this patient population. STUDY DESIGN: A prospective pilot open-label randomized trial. SETTING & PARTICIPANTS: 65 patients receiving maintenance peritoneal dialysis with advanced SHPT recruited from 2 university-affiliated hospitals in Hong Kong. INTERVENTIONS: Total parathyroidectomy with forearm autografting versus oral cinacalcet treatment for 12 months. OUTCOME: Prespecified secondary end points including changes in BMD z and T scores of femoral neck, lumbar spine, and distal radius 12 months after treatment initiation and also categorized as osteopenia or osteoporosis according to the World Health Organization. RESULTS: Both total parathyroidectomy and cinacalcet significantly improved BMD of the lumbar spine and femoral neck over 12 months, but the total parathyroidectomy group had a greater increase than the cinacalcet-treated group (P<0.001). The proportion of study participants classified as having osteopenia/osteoporosis by femoral neck T-score fell from 78.2% to 51.7% in the total parathyroidectomy group (P<0.001) and from 65.7% to 52.0% in cinacalcet-treated group after 12 months (P=0.7). The proportion of participants with a T-score at the lumbar spine classified as osteopenia/osteoporosis fell from 53.1% to 31.0% in the total parathyroidectomy group (P=0.01) and from 59.4% to 53.8% with cinacalcet (P=0.3). No significant change was observed in BMD T or z score of the distal radius over 12 months with either intervention. LIMITATIONS: Bone histology was not assessed, and the study duration was 12 months. CONCLUSIONS: A large proportion of peritoneal dialysis patients with advanced SHPT had low bone densities and osteopenia/osteoporosis. Total parathyroidectomy increased the BMD of the lumbar spine and femoral neck and reduced osteopenia/osteoporosis more than oral cinacalcet. FUNDING: Grants from academic (The University of Hong Kong Research) and not-for-profit (Hong Kong Society of Nephrology) entities. REGISTRATION: Registered at Clinicaltrials.gov with study number NCT01447368. PLAIN-LANGUAGE SUMMARY: It is not known whether oral cinacalcet and surgical parathyroidectomy differ in their effects on bone parameters in patients with advanced secondary hyperparathyroidism (SHPT) receiving peritoneal dialysis. This pilot randomized trial evaluated the effect of medical versus surgical therapy on bone mineral densities (BMD) as prespecified secondary study end points. The findings showed that a large proportion of peritoneal dialysis patients with advanced SHPT had low bone densities and osteopenia/osteoporosis. Parathyroidectomy increased the BMD of the lumbar spine and femoral neck more than cinacalcet over 12 months. Parathyroidectomy reduced the proportion of patients with osteopenia/osteoporosis at the lumbar spine and femoral neck more than cinacalcet after 12 months. Neither intervention led to an increase in the BMD of the distal radius over 12 months.

Predictive Ability of Rule of 3 in Parathyroid Cancer: Outcomes from a South Asian Cohort.

BACKGROUND: Preoperative diagnosis of parathyroid cancer (PC) where possible allows for en-bloc resection of the tumour, which is associated with excellent prognosis. The rule of >3 (size of tumour larger than 3 cm; corrected calcium more than 3 mmol/L) as proposed by Schulte and Talat has a specificity of 95% in predicting malignancy in parathyroid neoplasms. We looked at the impact of rule of 3 in predicting malignancy and outcomes on intervention in a South Asian cohort. METHODS: Patients who underwent parathyroid surgery between 2010 and 2023 at two tertiary referral centres were assessed. Patients with PC were selected and their clinicopathological parameters, treatment modalities, and outcomes were analysed. RESULTS: Thirteen of 336 (3.8%) patients with a mean age of 61.8 (±17.5) years were diagnosed with PC during the study period. The highest mean preoperative values were PTH (92.4 ± 66.27 pmol/L), highest corrected calcium (3.21 ± 0.28 mmol/L), and alkaline phosphatase (419 IU/mL). Nine patients underwent en-bloc excision while the other had focussed parathyroidectomy. Recurrences were recorded in 2 (28.5%) patients over a mean follow-up period of 69 (±48.6) months. One patient with lung metastasis underwent video-assisted thoracic surgery. There was no disease specific mortality in this cohort during the study period. CONCLUSIONS: In our experience, the predictive rule of 3 has low sensitivity to suspect PC preoperatively, resulting in limited usefulness in clinical practice. Outcomes appear to be less favourable with higher recurrence rates in cases where less than en-bloc resection is performed.

Cost-Effectiveness and Clinical Outcomes of Secondary Hyperparathyroidism Treatments in Patients with Chronic Kidney Disease.

The study addresses the challenge of treating secondary hyperparathyroidism (SHPT) in chronic kidney disease (CKD) patients, focusing on the cost-effectiveness of surgical versus pharmacological interventions. Conducting a retrospective analysis on 152 CKD patients with SHPT at the Third People's Hospital of Chengdu, the study matched 80 patients into two groups: 40 undergoing parathyroidectomy with autotransplantation (PTX + AT) and 40 treated with calcimimetics. PTX + AT was more effective in alleviating symptoms, particularly bodily pain, and demonstrated greater cost-effectiveness over a long-term period compared to calcimimetics. This was especially significant in patients with PTH levels > 1800 pg/mL and hyperphosphatemia. Despite similar initial costs, PTX + AT led to a substantial decrease in expenses during the 2-5 years post-treatment period, PTX + AT results in an ICER of -RMB 26.71/QALY for the first post-treatment year and -RMB-111.9k/QALY for the 2-5 year period, indicating cost-effectiveness with reduced long-term costs. The study also found an increased economic burden in managing patients with hyperphosphatemia. Surgical intervention (PTX + AT) is advocated as the primary treatment strategy for severe SHPT in CKD patients, owing to its long-term economic and clinical advantages. The results underscore the need for a severity-based approach in treating SHPT.

Modern Trends for Primary Hyperparathyroidism: Intervening on Less Biochemically Severe Disease.

INTRODUCTION: Primary hyperparathyroidism (PHPT) is defined by autonomous parathyroid hormone secretion, which has broad physiologic effects. Parathyroidectomy is the only cure and is recommended for patients demonstrating symptomatic disease and/or end organ damage. However, there may be a benefit to intervening before the development of complications. We sought to characterize institutional trends in the biochemical and symptomatic presentation of PHPT and the associated cure and complication rates. METHODS: We performed a retrospective cohort study of 1087 patients undergoing parathyroidectomy for PHPT, evaluating patients at 2-year intervals between 2002 and 2019. We identified signs and symptoms of PHPT based on the 2016 American Association of Endocrine Surgery Guidelines. Trends were evaluated with Kruskal Wallis, Chi-square tests, and Fisher's exact tests. RESULTS: Patients with PHPT are presenting with lower parathyroid hormone (P = 0.0001) and calcium (P = 0.001) in the current era. Parathyroidectomy is more commonly performed for borderline guideline concordant patients with osteopenia (40.2%) and modest calciuria (median 246 mg/dL/24 h). 93.7% are cured, with no difference over time or between groups by guideline concordance. CONCLUSIONS: Parathyroidectomy is increasingly performed for patients who demonstrate modest bone and renal dysfunction. Patients experience excellent cure rates and rarely experience postoperative hypocalcemia, suggesting a role for broader surgical indications.

Patient Neighborhood Adversity Associated With Access Not Wait Time to Parathyroidectomy.

INTRODUCTION: Delays to treatment of primary hyperparathyroidism (PHPT) escalates patient morbidity, which particularly affects individuals from under-resourced areas already facing health disparities. We hypothesized that PHPT patients from socially and economically deprived areas encounter longer waits to surgery. METHODS: Utilizing a prospectively maintained database, we identified PHPT patients aged ≥18 undergoing initial parathyroidectomy between 2013 and 2022 at an academic, tertiary care center. Patient's social and economic advantage levels were classified into deciles using the Area Deprivation Index (ADI), which accounts for 17 social determinants of health. The time from first hypercalcemic value to surgery was compared across ADI groups via linear regression, controlling for pertinent care process factors. RESULTS: Among 1132 patients, 68.9% were from low, 19.1% from medium, and 12.0% from high-disadvantage areas, diverging from the hospital's catchment population (55.2%, 26.6%, and 18.1%, respectively, P < 0.01). Patients from high-disadvantage areas exhibited higher comorbidity rates (55.2% versus 38.2%, P < 0.01) and were predominantly rural residents (66.2% vs. 5.8%, P < 0.01) compared to low-disadvantage areas. Similar biochemical and clinical features were shown across ADI groups. The median time from abnormal calcium to surgery was 648 d (IQR 543-753), with high-disadvantage patients experiencing a median treatment delay of 527 d, compared to 657 and 633 d for medium and low-disadvantage patients, respectively (P = 0.38). Linear regression analysis showed no association between ADI and treatment delay. CONCLUSIONS: The high-disadvantage group underwent parathyroidectomy at lower rates than expected, but there were no significant delays in surgery among disadvantaged patients who were ultimately treated. This suggests that while social determinants may correlate to care access, they do not necessarily prolong treatment for those with established care.

Pre-Transplant Calcimimetic Use and Dose Information Improves the Accuracy of Prediction of Tertiary Hyperparathyroidism after Kidney Transplantation: A Retrospective Cohort Study.

Tertiary hyperparathyroidism (THPT) is characterized by elevated parathyroid hormone and serum calcium levels after kidney transplantation (KTx). To ascertain whether pre-transplant calcimimetic use and dose information would improve THPT prediction accuracy, this retrospective cohort study evaluated patients who underwent KTx between 2010 and 2022. The primary outcome was the development of clinically relevant THPT. Logistic regression analysis was used to evaluate pre-transplant calcimimetic use as a determinant of THPT development. Participants were categorized into four groups according to calcimimetic dose, developing two THPT prediction models (with or without calcimimetic information). Continuous net reclassification improvement (CNRI) and integrated discrimination improvement (IDI) were calculated to assess ability to reclassify the degree of THPT risk by adding pre-transplant calcimimetic information. Of the 554 patients, 87 (15.7%) developed THPT, whereas 139 (25.1%) received pre-transplant calcimimetic treatment. Multivariate logistic regression analysis revealed that pre-transplant calcimimetic use was significantly associated with THPT development. Pre-transplant calcimimetic information significantly improved the predicted probability accuracy of THPT (CNRI and IDI were 0.91 [p < 0.001], and 0.09 [p < 0.001], respectively). The THPT prediction model including pre-transplant calcimimetic information as a predictive factor can contribute to the prevention and early treatment of THPT in the era of calcimimetics.

Patient-reported outcome measures for primary hyperparathyroidism: a systematic review of measurement properties.

BACKGROUND: The quality of patient-reported outcome measures (PROMs) used to assess the outcomes of primary hyperparathyroidism (PHPT), a common endocrine disorder that can negatively affect patients' health-related quality of life due to chronic symptoms, has not been rigorously examined. This systematic review aimed to summarize and evaluate evidence on the measurement properties of PROMs used in adult patients with PHPT, and to provide recommendations for appropriate measure selection. METHODS: After PROSPERO registration (CRD42023438287), Medline, EMBASE, CINAHL Complete, Web of Science, PsycINFO, and Cochrane Trials were searched for full-text articles in English investigating PROM development, pilot studies, or evaluation of at least one PROM measurement property in adult patients with any clinical form of PHPT. Two reviewers independently identified studies for inclusion and conducted the review following the Consensus-Based Standards for the Selection of Health Measurement Instruments (COSMIN) Methodology to assess risk of bias, evaluate the quality of measurement properties, and grade the certainty of evidence. RESULTS: From 4989 records, nine PROM development or validation studies were identified for three PROMs: the SF-36, PAS, and PHPQoL. Though the PAS demonstrated sufficient test-retest reliability and convergent validity, and the PHPQoL sufficient test-retest reliability, convergent validity, and responsiveness, the certainty of evidence was low-to-very low due to risk of bias. All three PROMs lacked sufficient evidence for content validity in patients with PHPT. CONCLUSIONS: Based upon the available evidence, the SF-36, PAS, and PHPQoL cannot currently be recommended for use in research or clinical care, raising important questions about the conclusions of studies using these PROMs. Further validation studies or the development of more relevant PROMs with strong measurement properties for this patient population are needed.

Identification of novel risk factors for postoperative severe hypocalcemia in patients with primary hyperparathyroidism undergoing parathyroidectomy: a case control study.

BACKGROUND: Patients with primary hyperparathyroidism (PHPT) are at risk for severe hypocalcemia (SH) following parathyroidectomy (PTX), but limited data exist on the predictors of SH. We aimed to identify risk factors for early postoperative SH after PTX in patients with PHPT and to evaluate the predictive value of clinical parameters. METHODS: A retrospective review of patients with PHPT who underwent PTX between January 2010 and December 2022 was performed. A total of 46 patients were included in the study, with 15 (32.6%) experiencing postoperative SH, 19 (41.3%) having calculi in the ureter or kidney, and 37 (80.4%) having osteoporosis. Patients were divided into SH and non-SH groups based on postoperative serum calcium levels. Preoperative biochemical indicators, bone turnover markers, and renal function parameters were analyzed and correlated with postoperative SH. RESULTS: Statistically significant (P < 0.05) differences were found in preoperative serum calcium (serum Ca), intact parathyroid hormone, serum phosphorus (serum P), serum Ca/P, percentage decrease of serum Ca, total procollagen type 1 intact N-terminal propeptide, osteocalcin (OC), and alkaline phosphatase levels between the two groups. Multivariate analysis showed that serum P (odds ratio [OR] = 0.989; 95% confidence interval [95% CI] = 0.981-0.996; P = 0.003), serum Ca (OR = 0.007; 95% CI = 0.001-0.415; P = 0.017), serum Ca/P (OR = 0.135; 95% CI = 0.019-0.947; P = 0.044) and OC levels (OR = 1.012; 95% CI = 1.001-1.024; P = 0.036) were predictors of early postoperative SH. The receiver operating characteristic curve analysis revealed that serum P (area under the curve [AUC] = 0.859, P < 0.001), serum Ca/P (AUC = 0.735, P = 0.010) and OC (AUC = 0.729, P = 0.013) had high sensitivity and specificity. CONCLUSION: Preoperative serum P, serum Ca/P and osteocalcin levels may identify patients with PHPT at risk for early postoperative SH after PTX.

Characteristics, management and outcomes of primary hyperparathyroidism from 2009 to 2021: a single centre report from South Africa.

BACKGROUND: There has been a notable shift towards the diagnosis of less severe and asymptomatic primary hyperparathyroidism (PHPT) in developed countries. However, there is a paucity of recent data from sub-Saharan Africa (SSA), and also, no reported data from SSA on the utility of intra-operative parathyroid hormone (IO-PTH) monitoring. In an earlier study from Inkosi Albert Luthuli Central Hospital (IALCH), Durban, South Africa (2003-2009), majority of patients (92.9%) had symptomatic disease. The aim of this study was to evaluate the clinical profile and management outcomes of patients presenting with PHPT at IALCH. METHODS: A retrospective chart review of patients with PHPT attending the Endocrinology clinic at IALCH between July 2009 and December 2021. Clinical presentation, laboratory results, radiologic findings, surgical notes and histology were recorded. RESULTS: Analysis included 110 patients (87% female) with PHPT. Median age at presentation was 57 (44; 67.5) years. Symptomatic disease was present in 62.7% (n:69); 20.9% (n:23) had a history of nephrolithiasis and 7.3% (n:8) presented with previous fragility fractures. Mean serum calcium was 2.87 ± 0.34 mmol/l; median serum-PTH was 23.3 (15.59; 45.38) pmol/l, alkaline phosphatase 117.5 (89; 145.5) U/l and 25-hydroxyvitamin-D 42.9 (33.26; 62.92) nmol/l. Sestamibi scan (n:106 patients) identified an adenoma in 83.02%. Parathyroidectomy was performed on 84 patients with a cure rate of 95.2%. Reasons for conservative management (n:26) included: no current surgical indication (n:7), refusal (n:5) or deferral of surgery (n:5), loss to follow-up (n:5) and assessed as high anaesthetic risk (n:4). IO-PTH measurements performed on 28 patients indicated surgical success in 100%, based on Miami criteria. Histology confirmed adenoma in 88.1%, hyperplasia in 7.1% and carcinoma in 4.8%. Post-operative hypocalcaemia developed in 30 patients (35.7%), of whom, 14 developed hungry bone syndrome (HBS). In multivariate analysis, significant risk factors associated with HBS included male sex (OR 7.01; 95% CI 1.28, 38.39; p 0.025) and elevated pre-operative PTH (OR 1.01; 95% CI 1.00, 1.02; p 0.008). CONCLUSIONS: The proportion of asymptomatic PHPT has increased at this centre over the past decade but symptomatic disease remains the dominant presentation. Parathyroidectomy is curative in the majority of patients. IO-PTH monitoring is valuable in ensuring successful surgery.

Same-day parathyroidectomy for primary hyperparathyroidism -an over 20-year practice.

INTRODUCTION: There has been a shift in recent years toward same-day parathyroidectomies due to the decrease in mutual costs with few significant differences in postoperative morbidity or mortality. We sought to determine if demographics, preoperative patient risk factors, or comorbidities were associated with a patient's likelihood of having same-day or inpatient surgery. MATERIALS AND METHODS: A prospective database of parathyroid operations from 2001 to 2022 (n = 2948 patients) was reviewed for surgeries completed for primary hyperparathyroidism. Patients were categorized as same-day or inpatient surgery; demographics, risk factors, and co-morbidities were examined and differences across practice patterns during the 21-year period were studied and also analyzed in a subset of patients from 2013 to 2022. RESULTS: In a recent subset of patients from 2013 to 2022, patients having inpatient surgery were more likely to be Black and use anticoagulation or antiplatelet therapy. Multivariable regression confirmed increased odds of aging and black patients requiring inpatient parathyroidectomy. Compared to 2001-2003, there was a significantly increased proportion of patients undergoing same-day surgery; compared to 2010-2012, there was a similar proportion of patients undergoing outpatient surgery between 2013 and 2018, and there was an increased proportion from 2019 through 2022. CONCLUSION: Same-day parathyroidectomies have been shown to be safe and has become the typical practice for high-volume parathyroid surgeons over the last decade. Complications such as postoperative hematoma or hypocalcemia were previously shown to be incompletely mitigated by increased LOS or inpatient surgery, although demographics are considered to increase the odds of inpatient parathyroidectomy.

Risk of neuropsychiatric disorders in primary hyperparathyroidism: Parathyroidectomy versus nonoperative management.

BACKGROUND: Neuropsychiatric disorders frequently manifest in primary hyperparathyroidism (PHPT), yet evidence of parathyroidectomy's benefit remains mixed. We sought to compare the incidence of neuropsychiatric disorders among patients treated with parathyroidectomy versus nonoperative management. METHODS: We retrospectively reviewed our institutional administrative database for patients with PHPT. Patients with secondary hyperparathyroidism were excluded. The date of biochemical diagnosis of PHPT was designated as day 0 and new-onset neuropsychiatric disorders were defined as conditions diagnosed after this date. The risk of new-onset neuropsychiatric disorders in propensity score-matched surgical and nonsurgical patients was compared using the Cox regression over a median follow-up of 4.2 years. RESULTS: Our cohort included 3728 patients, predominantly female (78%) and white (63.9%), with a mean (± Standard deviation) age of 62 ± 14 years. Of these, 1704 (45.7%) underwent parathyroidectomy. After propensity score matching and adjusting for clinical characteristics, patients who had parathyroidectomy showed a reduced hazard ratio (HR) for new-onset cognitive impairment (HR: 0.65, 95% CI: 0.47-0.91), somnolence (HR: 0.45, 95% CI: 0.23-0.9) and schizophrenia (HR: 0.08, 95% CI: 0.01-0.6), but not for anxiety (HR: 1.07, 95% CI: 0.83-1.37), depression (HR: 1.02, 95% CI: 0.77-1.36) or suicidal ideation (HR: 0.31, 95% CI: 0.04-2.71). Additionally, surgical patients were less likely to require inpatient care (0.3% vs. 1.8%, p < 0.001) for neuropsychiatric disorders. CONCLUSIONS: Parathyroidectomy is associated with lower risks of new-onset cognitive impairment, schizophrenia, or somnolence, indicating potential benefit of operative management in improving neuropsychiatric symptoms in patients with PHPT.

Assessment of left ventricular dysfunction by strain echo in primary hyperparathyroidism and its reversal after parathyroidectomy.

BACKGROUND: Strain echocardiography is a highly sensitive modality for detecting myocardial disease at an early stage. Therefore, we aim to evaluate subclinical left ventricular dysfunction in primary hyperparathyroidism (PHPT) patients with myocardial strain imaging in addition to conventional echocardiography and to look for its reversal after parathyroidectomy (PTx). METHODS: Thirty patients who underwent curative parathyroidectomy for PHPT were included. All patients were evaluated with M mode echo, 2D echo and strain imaging before and 6 months after PTx. Left ventricular ejection fraction, left ventricular diastolic dysfunction, left ventricular hypertrophy (LVH), Global Longitudinal Strain (GLS) and global circumferential strain (GCS) were recorded. RESULTS: On M mode echo, LVH was present in 15 patients and 8 of them improved completely after PTx (p < 0.038). Incidence of systolic and diastolic dysfunction on 2D echo was 10% and 13.3% respectively; while myocardial strain imaging showed impaired systolic function in 46.7% patients. Hence, compared to conventional 2D echo, strain imaging showed 36.7% high detection rate of subnormal cardiac function. There was improvement in left ventricle dysfunction (p = 0.083), GLS and GCS (p = 0.034) after PTx. Serum parathormone demonstrated a strong positive correlation with change in GLS and GCS (p = 0.013, p = 0.126) while serum calcium showed a weak correlation with change in GLS and GCS following surgery. CONCLUSION: Myocardial strain imaging should be considered for all PHPT patients as early identification of subclinical ventricle dysfunction provides an opportunity for an early intervention and thereby preventing development of irreversible LV dysfunction.

Surgical strategy in lithium-associated hyperparathyroidism: A population-based study.

BACKGROUND: The extent of parathyroidectomy (PTX) recommendation in patients with lithium-associated hyperparathyroidism (LAH) remains controversial. The primary objectives of this study were to analyze extent of surgery, complications, and long-term outcomes. METHODS: A population-based study, including all primary hyperparathyroidism (PHPT) patients who underwent PTX in Sweden between 2008 and 2017. Data on exhibited lithium prescriptions, morbidity, surgical approach, and outcomes were collected from relevant national registers and the Scandinavian Quality Register of Thyroid, Parathyroid, and Adrenal Surgery. Patients with lithium exposure before PTX were defined as having LAH. Descriptive summary statistics and regression models were used to evaluate differences in comorbidities, surgical approach, and outcomes between LAH and PHPT not exposed to lithium (non-LAH). RESULTS: Lithium exposure was significantly more common among PHPT (n = 202, 2.3%) than in controls (n = 416, 0.5%); OR 5.0 (95% CI 4.2-5.9). The risk of LAH correlated to the length of lithium exposure. In the LAH-group, the surgical procedures were more extensive and associated with a higher risk of postoperative bleeding, wound infections, persistent hypercalcemia, and hypocalcemia that remained after adjustment for the higher percentage of multiglandular disease. However, the cumulative risk of re-admission for PHPT was similar the first years after PTX and primarily elevated for patients with >5 years duration of lithium exposure prior to surgery. CONCLUSIONS: The findings support the perception of LAH as a complex entity. We recommend a functionally oriented approach, aimed to obtain and maintain normocalcemia for as long as possible, minimizing the risk of permanent hypoparathyroidism, and accepting some risk of recurrence.

The Effects of Parathyroidectomy vs Medical Treatments for Secondary Hyperparathyroidism in Patients Undergoing Dialysis: A Meta-Analysis.

OBJECTIVE: The management of secondary hyperparathyroidism in patients undergoing dialysis is debated, with uncontrolled parathyroid hormone (PTH) levels becoming more common despite the expanded use of medical treatments like cinacalcet. This study examines the clinical benefits of parathyroidectomy vs medical treatment in reducing mortality and managing key laboratory parameters in patients undergoing dialysis. METHODS: PubMed, Embase, Cochrane, Scopus, and Web of Science databases were searched for cohort studies or randomized controlled trials published before August 18, 2023. We included studies with comparative arms, specifically medical treatment vs surgical intervention. Patients with a history of kidney transplant were excluded. Outcomes were analyzed using hazard ratios (HRs) for mortality and weighted mean differences (WMD) for laboratory parameters. RESULTS: Twenty-three studies involving 24 398 patients were analyzed. The pooled meta-analysis has shown a significant reduction in all-cause (HR, 0.47; 95% confidence interval [CI], 0.35-0.61) and cardiovascular mortality (HR, 0.58; 95% CI, 0.40-0.84) for parathyroidectomy vs medical treatments. Subgroup analysis showed that parathyroidectomy was associated with a greater reduction in mortality in patients with a PTH level over 585 pg/mL (HR, 0.37; 95% CI, 0.24-0.58). No mortality difference was found when all patients in the medical group received cinacalcet alongside standard medical treatment (HR, 1.02; 95% CI, 0.49-2.11). Parathyroidectomy also led to a larger decrease in PTH (WMD, 1078 pg/mL; 95% CI, 587-1569), calcium (WMD, 0.86 mg/dL; 95% CI, 0.43-1.28), and phosphate (WMD, 0.74 mg/dL; 95% CI, 0.32-1.16). CONCLUSION: Parathyroidectomy may offer a survival advantage compared to medical management in patients with severe secondary hyperparathyroidism.

Primary Hyperparathyroidism: Assessment of the Effects of Parathyroidectomy Using Dual X-Ray Absorptiometry, Trabecular Bone Score, and Dual X-Ray Absorptiometry-Based Three-Dimensional Modeling.

OBJECTIVE: This study aimed to evaluate the bone microstructure to determine whether curative surgery of primary hyperparathyroidism produces changes in bone mineral density (BMD), trabecular bone score (TBS), and three-dimensional (3D) dual x-ray absorptiometry (DXA) parameters and whether these changes are comparable. METHODS: We retrospectively studied 85 patients (60 women and 25 men, 60.4 ± 12.5 years) diagnosed with primary hyperparathyroidism and undergoing parathyroidectomy. Mean percent changes in BMD (lumbar spine [LS], femoral neck [FN], total hip [TH], and 1/3 radius), TBS and 3D-DXA parameters (trabecular volumetric BMD (vBMD), cortical vBMD, integral vBMD, cortical surface density (sBMD), and cortical thickness at TH) after surgery (12, 24, and/or 36 months) were calculated and compared, and we sought the determinants of these changes. RESULTS: After parathyroidectomy, BMD presented statistically significant mean increases in LS, FN, and TH during the first 3 years after surgery (P < .001), accompanied by an improvement in all 3D-DXA parameters, but there were no significant changes in 1/3 radius BMD or TBS. Cortical sBMD, trabecular vBMD, and integral vBMD reached mean increases of similar magnitude to those of FN and TH BMD. Age and preoperative serum levels of parathyroid hormone and carboxy-terminal telopeptide of type 1 collagen were significantly associated with percent changes after surgery. CONCLUSION: We found a benefit of parathyroidectomy for bone, with significant percent increases in LS, FN, and TH BMD up to the third year after surgery, and a qualitative benefit for the hip in both its trabecular and cortical compartments and bone strength.

Parathyroidectomy reduces inflammatory cytokines and increases vitamin D metabolites in patients with primary hyperparathyroidism.

CONTEXT: Primary hyperparathyroidism (PHPT) is accompanied by a decreased 25-hydroxyvitamin D (25OHD) and vitamin D binding protein (DBP). High parathyroid hormone (PTH) is associated with elevated interleukin-6 (IL-6) and monocyte chemoattractant protein-1 (MCP-1), yet the role of parathyroidectomy (PTX) on DBP and cytokines is not clear. OBJECTIVE: To prospectively evaluate the effect of PTX on inflammatory profiles, total and free 25OHD, and DBP in patients with PHPT. METHODS: Newly diagnosed patients with PHPT were recruited in the study (n=70). Twenty-eight patients returned after PTX, 3 months later. Biochemical markers were measured before and after PTX. A group of age and BMI-matched healthy subjects were included as controls (n=70). RESULTS: Prior to PTX, patients had lower serum DBP (37.5±6.0 vs 41.5±6.1mg/dL, p<0.001) and total 25OHD (30.1±9.5 vs 33.3±7.9ng/mL, P<0.05), but similar free 25OHD when compared to controls. Serum IL-6, C-reactive protein (CRP), and MCP-1 were higher in PHPT patients (p<0.05), whereas interleukin-10 (IL-10) was similar to controls. PTX increased total and free 25OHD and DBP (p<0.001), and decreased serum IL-6 and MCP-1 (p<0.05), but not CRP and IL-10. Multiple regression analysis indicated that the preoperative PTH explained a significant portion of the variance of IL-6 and MCP-1 (p<0.05). CONCLUSIONS: These findings suggest that PTH may upregulate the production of MCP-1 and IL-6 and downregulate circulating DBP in patients with PHPT, that are normalized by PTX. The exact effect of IL-6 and MCP-1 on DBP, vitamin D metabolites and the role on clinical outcomes in patients with PHPT is an area requiring further study.

Restless leg syndrome as a complication of primary hyperparathyroidism: insights from a retrospective study.

INTRODUCTION: Restless leg syndrome (RLS) is an invalidating neurological disorder with a complex, largely unknown pathophysiology. While RLS is observed in Parkinson's disease and in renal failure, idiopathic cases are common. Limited reports associate RLS with parathyroid hormone (PTH). This study analyzes a cohort of patients with primary hyperparathyroidism (PHPT) and chronic post-surgical hypoparathyroidism (hypo PTH), to investigate RLS prevalence, and associated risk factors. METHODS: Ninety-five patients (54 PHPT, 41 hypo PTH) were consecutively enrolled at the bone metabolism outpatient clinic. The revised IRLSSG diagnostic criteria were used to diagnose RLS, with assessments conducted through face-to-face interviews and neurological examination. When RLS was confirmed, the RLS severity scale was applied. Retrospective records included calcium-phosphate metabolism-related parameters, surgery details, renal lithiasis, fragility fractures, and densitometric features (T-score). RESULTS: RLS was diagnosed in 22.2% PHPT patients, compared to 4.9% of patients with hypo PTH (p = 0.02). Of RLS diagnosed patients, 91.7% had a history of parathyroidectomy, compared to 47.6% of patients without RLS (p = 0.01). Most of the operated patients reported that surgery determined an improvement of symptoms; however, mean score severity of RLS at our evaluation was 15/40, defined as moderate. PTH and calcium levels were not statistically associated to the presence of RLS. CONCLUSION: Our study suggests that PHPT may be one of the etiologies of RLS. Parathyroidectomy alleviates symptoms in the vast majority of the cases but does not remove them.

Prevalence, risk factors and effect of curative parathyroidectomy on nephrocalcinosis in Asian-Indian patients with symptomatic primary hyperparathyroidism.

Primary hyperparathyroidism (PHPT) is characterized by inappropriate secretion of parathyroid hormone, causing hypercalcemia and hypercalciuria, leading to renal stone diseases and nephrocalcinosis. The frequency, risk factors, and curative effect on nephrocalcinosis in post-parathyroidectomy have not been identified yet. Therefore, the present study evaluated the clinico-biochemical, radiological parameters and curative effect on nephrocalcinosis. A total of 583 PHPT patients were analysed in four groups viz. Group 1 (PHPT with nephrocalcinosis-98; 16.8%); Group 2 (PHPT with nephrolithiasis-227; 38.9%); Group 3 (PHPT with both nephrolithiasis and nephrocalcinosis-59; 10.1%); and Group 4 (PHPT without renal diseases-199, 34.1%). In the sub-group analysis, younger age (p ≤ 0.05), male gender (p ≤ 0.05), and hematuria (p ≤ 0.005) were significant in Group 1 vs. Group 4. Dysuria and low eGFR were significant in Group 1 vs. Group 2 (p ≤ 0.0005; p ≤ 0.05) and Group 1 vs. Group 4 (p ≤ 0.0005; p ≤ 0.0005). Polyuria (p ≤ 0.05; p ≤ 0.05, p ≤ 0.005), and gravluria (p ≤ 0.05; p ≤ 0.0005, p ≤ 0.005) were frequent in Group 1 vs. other groups. A significant difference was observed in S.Ca and, 24-hrs U.Ca in Group 1 vs. Group 2 {(12.2 (10.8-13.4) vs. 11.2 (10.7-12.4), p ≤ 0.05; 301 (189.5-465) vs. 180 (92.5-323.1), p ≤ 0.05} and Group 1 vs. Group 4 {(12.2 (10.8-13.4) vs. 11.4 (10.7-12.5), p ≤ 0.05 ; 301 (189.5-465) vs. 213 (110-360), p ≤ 0.0005}. Multivariate logistic regression showed gravluria [aOR = 9.2, p = 0.0001], S.Ca (aOR = 1.30, p = 0.003) and, 24-hrs U.Ca (aOR = 1.02, p = 0.042) to be independent predictors of nephrocalcinosis. Pre and post-operative assessment revealed decreased S. Ca levels [(11.9 ± 1.9) vs. (10.5 ± 1.0) mg/dL; p = 0.04] and complete radiological resolution (10.4%) in PHPT with nephrocalcinosis. Therefore, serum calcium, 24-hrs Urinary calcium, and gravluria were independent predictors of nephrocalcinosis with 10.4% showing complete radiological resolution post-operatively.

FT4 is a novel indicator for risk assessment of severe hypocalcemia following parathyroidectomy.

OBJECTIVE: To analyze the risk factors associated with the development of severe hypocalcemia (SH) in patients who have undergone parathyroidectomy (PTX). METHODS: This research involved patients with chronic kidney disease-secondary hyperparathyroidism who underwent PTX between June 1, 2021, and May 31, 2023. SH was characterized by a serum total calcium (tCa) level below 1.8 mmol/L. This study aimed to analyze differences in preoperative laboratory findings and clinical manifestations between patients with and without SH. Logistic regression analysis was used to identify potential risk factors associated with the development of SH. RESULTS: The incidence of SH was 23% (n = 176). Significant differences were observed in free thyroxine (FT4), free triiodothyronine, alanine aminotransferase, osteocalcin, tCa, alkaline phosphatase (ALP), C-terminal cross-linked telopeptide of type I collagen, and parathyroid hormone between the SH and non-SH groups. The three independent risk factors for SH were tCa [odds ratio (OR) 0.063, 95% confidence interval (95% CI) 0.006-0.663], ALP (OR 1.003, 95% CI 1.001-1.005), and FT4 (OR 0.439, 95%CI 0.310-0.621). The area under the curve, sensitivity, specificity, and overall accuracy of this model were 0.904 (95% CI 0.856-0.952), 46.3%(95% CI 32.0%-61.3%), 94.8% (95% CI 89.7%-97.5%), and 83.5% (95% CI 77.3%-88.3%), respectively. CONCLUSION: The preoperative level of FT4 plays a crucial role in predicting the risk of SH after PTX. The combined FT4-ALP-tCa model demonstrates the ability to predict SH risk, providing valuable insights for customizing calcium supplementation strategies and improving clinical decision-making.

Cohort review of patients with parathyroid cancer in End Stage Renal Disease (ESRD).

BACKGROUND AND HYPOTHESIS: Parathyroid carcinoma (PTTC) is a rare malignant endocrine tumor seen in up to 1-2% of all cases of primary hyperparathyroidism. However, incidence of parathyroid carcinoma in renal hyperparathyroidism is a rare phenomenon. We aimed to evaluate the outcomes of PTTC in renal hyperparathyroidism published in the literature. METHODS: Cohort review of parathyroid cancer cases reported in Medline (via PubMed), COCHRANE and EMBASE between the period 1985 - 2023 in patients with renal hyperparathyroidism. RESULTS: A total of 48 patients (20 M: 28F), with a mean age of 49.8 (± 11.7 SD: range 20-75) years. Dialysis vintage was for a period of 8.9 (± 7.2; range 6 months to 40 years). The mean preoperative values were as follows: serum corrected calcium-2.87 IQR 2.56-3.01), PTH - 221.8 (IQR 86.6 -257.2 pmol/L) and serum phosphate - 2.07 (IQR 1.72-2.28) mmol/L. Preoperative imaging was in the form of ultrasound of the neck in 21 of 48 (44%), MIBI scan in 27/48 (56%), contrast enhanced computerized tomography in 14/48 (29%) and MRI neck in 1/48 (2%). The mean size of the cancer was 2.7 (± 1.35) cm and weight of the gland ranged between 0.9 to 4.98 g. 18/48 (37%) patients underwent a total parathyroidectomy and 30/48 (63%) had subtotal parathyroidectomy. En bloc excision of the tumour along with the thyroid along and central compartment lymph nodes was only performed in 12/48 (25%), of whom 9 (19%) had it performed at index surgery, whereas in the rest was done for persistent or recurrent disease. After a mean follow up of 34 months, 14 (29%) had local recurrence, 1 (2%) had distant metastasis to the skeletal system, and 12 (25%) to the lungs. Cohort mortality was 6 (13%) due to refractory hypercalcemia. CONCLUSIONS: Parathyroid carcinoma in renal hyperparathyroidism is rare but when encountered, en bloc excision with parathyroidectomy provides the best chance of cure. Recurrences can be difficult to treat but may be needed to treat intractable hypercalcaemia.