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Journal of Bone and Mineral Research :... Nov 2022The last international guidelines on the evaluation and management of primary hyperparathyroidism (PHPT) were published in 2014. Research since that time has led to new... (Review)
Review
The last international guidelines on the evaluation and management of primary hyperparathyroidism (PHPT) were published in 2014. Research since that time has led to new insights into epidemiology, pathophysiology, diagnosis, measurements, genetics, outcomes, presentations, new imaging modalities, target and other organ systems, pregnancy, evaluation, and management. Advances in all these areas are demonstrated by the reference list in which the majority of listings were published after the last set of guidelines. It was thus, timely to convene an international group of over 50 experts to review these advances in our knowledge. Four Task Forces considered: 1. Epidemiology, Pathophysiology, and Genetics; 2. Classical and Nonclassical Features; 3. Surgical Aspects; and 4. Management. For Task Force 4 on the Management of PHPT, Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) methodology addressed surgical management of asymptomatic PHPT and non-surgical medical management of PHPT. The findings of this systematic review that applied GRADE methods to randomized trials are published as part of this series. Task Force 4 also reviewed a much larger body of new knowledge from observations studies that did not specifically fit the criteria of GRADE methodology. The full reports of these 4 Task Forces immediately follow this summary statement. Distilling the essence of all deliberations of all Task Force reports and Methodological reviews, we offer, in this summary statement, evidence-based recommendations and guidelines for the evaluation and management of PHPT. Different from the conclusions of the last workshop, these deliberations have led to revisions of renal guidelines and more evidence for the other recommendations. The accompanying papers present an in-depth discussion of topics summarized in this report. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
Topics: Humans; Hyperparathyroidism, Primary
PubMed: 36245251
DOI: 10.1002/jbmr.4677 -
Journal of Clinical & Translational... Jun 2023Primary hyperparathyroidism (PHPT) is the underlying etiology for 90% of patients with hypercalcemia. PHPT patients have traditionally been characterized as being...
PURPOSE
Primary hyperparathyroidism (PHPT) is the underlying etiology for 90% of patients with hypercalcemia. PHPT patients have traditionally been characterized as being symptomatic or asymptomatic. However, we submit that even "asymptomatic" patients may still have clinical features, posing the idea of coining asymptomatic disease as a misnomer. This paper presents a systematic review and meta-analysis elucidating the differences between asymptomatic and symptomatic PHPT in the literature.
METHODS
A comprehensive literature search was conducted in PubMed, Cochrane, and Web of Science databases for articles published from 2012 to 2022. Inclusion criteria consisted of all studies comparing symptomatic and asymptomatic PHPT patients. Two reviewers independently evaluated the literature using Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. The level of evidence was determined using the Oxford Center for Level of Evidence-Based Medicine. Data were extracted, and a meta-analysis was performed. I index was employed for heterogeneity.
RESULTS
There were 18 studies included, with a total of 4238 patients. The average age of patients included was 56.37, with 25.7% of the cohort being male. Several studies reported clinical features even for the "asymptomatic" group. Patients in the symptomatic group tended to have higher levels of PTH and calcium. The asymptomatic group had greater levels of vitamin D. There was observed heterogeneity between the studies.
CONCLUSIONS
More extreme PTH, calcium values, and low vitamin D levels were seen in patients with symptomatic disease. However, asymptomatic patients occasionally exhibited clinical features. Therefore, the terminology of "asymptomatic" disease is likely inappropriate for these patients.
PubMed: 37089759
DOI: 10.1016/j.jcte.2023.100317 -
Endocrine Connections Jul 2020Primary hyperparathyroidism (PHPT) is a common condition affecting people of all ages and is mainly treated with parathyroidectomy. Cinacalcet has been widely used in...
PURPOSE
Primary hyperparathyroidism (PHPT) is a common condition affecting people of all ages and is mainly treated with parathyroidectomy. Cinacalcet has been widely used in secondary or tertiary hyperparathyroidism, but the use of cinacalcet in PHPT is less clear.
METHODS
Searches were conducted in Medline and Embase for cinacalcet use in PHPT from induction to 10 April 2020. Articles and conferences abstracts describing the use of cinacalcet for PHPT in prospective or retrospective cohorts and randomized controlled trials restricted to English language only. We initially identified 1301 abstracts. Each article went extraction by two blinded authors on a structured proforma. Continuous outcomes were pooled with weight mean difference (WMD). Quality of included articles was assessed with Newcastle Ottwa Scale and Cochrane Risk of Bias 2.0.
RESULTS
Twenty-eight articles were included. Normalization rate of serum Ca levels was reported at 90% (CI: 0.82 to 0.96). Serum levels of Ca and PTH levels were significantly reduced (Ca, WMD: 1.647, CI: -1.922 to -1.371; PTH, WMD: -31.218, CI: -41.671 to -20.765) and phosphate levels significantly increased (WMD: 0.498, CI: 0.400 to 0.596) after cinacalcet therapy. The higher the baseline Ca levels, the greater Ca reduction with cinacalcet treatment. Age and gender did not modify the effect of cinacalcet on serum Ca levels.
CONCLUSION
The results from the meta-analysis support the use of cinacalcet as an alternative or bridging therapy to treat hypercalcemia in people with PHPT.
PubMed: 32621588
DOI: 10.1530/EC-20-0221 -
The Quarterly Journal of Nuclear... Jun 2023Primary hyperparathyroidism (pHPT) is a common endocrine disorder caused by an autonomous overproduction of parathyroid hormone (PTH) by a parathyroid gland. Over the... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Primary hyperparathyroidism (pHPT) is a common endocrine disorder caused by an autonomous overproduction of parathyroid hormone (PTH) by a parathyroid gland. Over the last decade, F-choline (FCH) PET has emerged as a highly performant imaging technique for guiding parathyroidectomy. As cure is the goal of surgery, the main aims of this study were to summarize patient-based sensitivity, positive predictive value (PPV), and cure rate of FCH PET guided surgery in the surgical management of pHPT.
EVIDENCE ACQUISITION
We conducted a systematic review and metaanalysis according to the PRISMA Guidelines. A literature search was performed in the PubMed, Web of Science and Cochrane databases, last updated November 2022. Original articles on choline PET in patients with pHPT mentioning patient-based sensitivity, PPV and cure rate were retained. Quality of included studies was assessed using the QUADAS-2 Tool. Patient-based sensitivity, PPV and cure rate were pooled by using a random-effects model.
EVIDENCE SYNTHESIS
Twenty-three studies including 1716 patients were included for quantitative assessment. FCH PET showed a pooled patient-based sensitivity of 93.8% (95% CI: 89.8-96.3) and PPV of 97% (95% CI: 92.8-98.8) in patients with pHPT. Parathyroid surgery was performed in 1129 patients. The pooled cure rate of PET-guided surgery was 92.8% (95% CI: 87.4-96.0). Heterogeneity was shown to be moderate for all effect sizes.
CONCLUSIONS
FCH PET showed a high patient-based sensitivity, PPV and cure rate of PET guided surgery in patients with pHPT.
Topics: Humans; Hyperparathyroidism, Primary; Parathyroid Glands; Choline; Positron-Emission Tomography; Positron Emission Tomography Computed Tomography
PubMed: 36756935
DOI: 10.23736/S1824-4785.23.03512-4 -
Calcified Tissue International Jul 2024This study aimed to evaluate the prevalence and risk of malignant neoplasm in primary hyperparathyroidism (PHPT) patients. Potentially eligible studies were retrieved... (Meta-Analysis)
Meta-Analysis Review
This study aimed to evaluate the prevalence and risk of malignant neoplasm in primary hyperparathyroidism (PHPT) patients. Potentially eligible studies were retrieved from PubMed and Embase databases from inception to November 2023 using search strategy consisting of terms for "Primary hyperparathyroidism" and "Malignant neoplasm". Eligible study must report prevalence of malignant neoplasm among patients with PHPT or compare the risk of malignant neoplasm between patients with PHPT and comparators. Point estimates with standard errors were extracted from each study and combined using the generic inverse variance method.A total of 11,926 articles were identified. After two rounds of systematic review, 50 studies were included. The meta-analysis revealed that pooled prevalence rates of overall cancer was 0.19 (95%CI: 0.13-0.25; I 94%). The two most prevalent types of malignancy among patients with PHPT ware papillary thyroid cancer (pooled prevalence: 0.07; 95%CI: 0.06-0.08; I 85%) and breast cancer (pooled prevalence: 0.05; 95%CI: 0.03-0.07; I 87%). Subgroup analysis of studies focusing on patients undergoing parathyroidectomy reported a fourfold higher prevalence of papillary thyroid cancer than the remaining studies (0.08 versus 0.02). The meta-analysis of cohort studies found a significant association between PHPT and overall cancer with the pooled risk ratio of 1.28 (95%CI: 1.23-1.33; I 66.9%).We found that the pooled prevalence of malignant neoplasm in PHPT was 19%, with papillary thyroid cancer and breast cancer being the most prevalent types. The meta-analysis of cohort studies showed that patient with PHPT carried an approximately 28% increased risk of malignancy.
Topics: Humans; Hyperparathyroidism, Primary; Risk Factors; Prevalence; Parathyroidectomy; Breast Neoplasms; Thyroid Cancer, Papillary; Thyroid Neoplasms
PubMed: 38772934
DOI: 10.1007/s00223-024-01219-y -
Medicine Oct 2017The aim of the study is to systematically review the evidence on post parathyroidectomy (PTX) changes as measured by echocardiogram (ECHO) in patients with primary... (Meta-Analysis)
Meta-Analysis Review
The aim of the study is to systematically review the evidence on post parathyroidectomy (PTX) changes as measured by echocardiogram (ECHO) in patients with primary hyperparathyroidism (PHPT).PHPT may increase risk of cardiovascular morbidity/mortality. Conclusions of studies assessing ECHO changes, pre versus post PTX, are inconsistent.A systematic literature search was conducted to locate published and unpublished studies. Randomized control trials, nonrandomized control trials, and observational studies were included. Variables were reported as means and standard deviations. An inverse variance statistical method, with random-effects analysis model, was applied to continuous data. The effect measure was standardized mean difference, confidence interval of 95%. Primary outcome measure was left ventricular ejection fraction (LVEF). Secondary outcome measures were left ventricular mass index (LVMI), peak early over peak late diastolic velocity ratio (E/A ratio), isovolumetric relaxation time (IVRT), intraventricular septal thickness (IVST), and posterior wall thickness (PWT).Fourteen studies were included. Follow-up time ranged 3 to 67 months. No significant differences (P > .05) in primary outcome measure LVEF (SMD = -0.03, CI = -0.24, 0.19), or secondary outcome measures E/A Ratio (SMD = -0.05, CI = -0.24, 0.14), IVST (SMD = 0, CI = 0.31, 0.32), PWT (SMD = 0.01, CI = -0.38, 0.39), LVMI (SMD = -0.18, CI = -0.74, 0.38), and IVRT (SMD = -0.84, CI = -1.83, 0.14) were observed.There was no significant difference in LVEF pre to post PTX. Due to heterogeneity of current literature, we were unable to determine if other outcome measures of cardiac function are affected after PTX in patients with PHPT. We recommend a randomized control trial be conducted to make concrete conclusions.
Topics: Echocardiography; Humans; Hyperparathyroidism, Primary; Parathyroidectomy; Ventricular Function, Left
PubMed: 29068975
DOI: 10.1097/MD.0000000000007255 -
Frontiers in Endocrinology 2023Primary hyperparathyroidism (PHPT) is characterized by increased bone remodeling and hypercalcemia. Parathyroidectomy (PTX), the current standard of care, is recommended... (Meta-Analysis)
Meta-Analysis
Efficacy of antiresorptive agents bisphosphonates and denosumab in mitigating hypercalcemia and bone loss in primary hyperparathyroidism: A systematic review and meta-analysis.
PURPOSE
Primary hyperparathyroidism (PHPT) is characterized by increased bone remodeling and hypercalcemia. Parathyroidectomy (PTX), the current standard of care, is recommended in all symptomatic and some groups of asymptomatic patients. Anti-resorptive therapies (bisphosphonates and denosumab) have been used in patients where PTX is refused or contraindicated. In this meta-analysis, we investigated the effectiveness of anti-resorptives in preventing/treating PHPT-induced bone loss and mitigating hypercalcemia.
METHOD
PubMed, Scopus, and Cochrane Library databases were searched for articles with keywords containing PHPT, bisphosphonates, and denosumab in various combinations. We extracted and tabulated areal BMD (aBMD), serum mineral, and bone turnover parameters from the qualified studies and used comprehensive meta-analysis software for analysis.
RESULTS
Of the 1,914 articles screened, 13 were eligible for meta-analysis. In the pooled analysis, 12 months of anti-resoptives (bisphosphonates and denosumab) therapy significantly increased aBMD at the lumbar spine (Standard difference in means (SDM)=0.447, 95% CI=0.230 to 0.664, p=0.0001), femoral neck (SDM=0.270, 95% CI=0.049 to 0.491, p=0.017) and increased serum PTH (SDM=0.489, 95% CI=0.139 to 0.839, p=0.006), and decreased serum calcium (SDM=-0.545, 95% CI=-0.937 to -0.154, p=0.006) compared with baseline. 12 months of bisphosphonate use significantly increased aBMD only at the lumbar spine (SDM=0.330, 95% CI=0.088 to 0.571, p=0.007) with a significant increased in serum PTH levels (SDM=0.546, 95% CI= 0.162 to 0.930, p=0.005), and a decreased in serum calcium (SDM=-0.608, 95% CI=-1.048 to -0.169, p=0.007) and bone-turnover markers (BTMs) compared with baseline. Denosumab use for 12 months significantly increased aBMD at both the lumbar spine (SDM=0.828, 95% CI=0.378 to 1.278, p=0.0001) and femur neck (SDM=0.575, 95% CI=0.135 to 1.015, p=0.010) compared with baseline. Mean lumbar spine aBMD (SDM=0.350, 95% CI=0.041 to 0.659, p=0.027) and serum PTH (SDM=0.602, 95% CI= 0.145 to 1.059, p=0.010) were significantly increased after 12 months of alendronate use compared with placebo. When compared with baseline, alendronate significantly decreased BTMs after 12 months and increased aBMD without altering the PTH and calcium levels after 24 months.
CONCLUSION
Anti-resorptives are effective in mitigating bone loss and hypercalcemia in PHPT while maintaining or increasing aBMD. PTX reversed all changes in PHPT and normalized PTH levels.
Topics: Humans; Bone Density Conservation Agents; Diphosphonates; Alendronate; Denosumab; Hypercalcemia; Calcium; Hyperparathyroidism, Primary; Bone Density; Parathyroid Hormone; Bone Diseases, Metabolic; Lumbar Vertebrae
PubMed: 36817591
DOI: 10.3389/fendo.2023.1098841 -
JAMA Otolaryngology-- Head & Neck... May 2022Emerging computed tomographic (CT) imaging techniques for the localization of primary hyperparathyroidism (PHPT) may be superior to the current imaging standard, thus... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Emerging computed tomographic (CT) imaging techniques for the localization of primary hyperparathyroidism (PHPT) may be superior to the current imaging standard, thus necessitating a critical review and pooling of available evidence.
OBJECTIVE
Primary hyperparathyroidism requires accurate imaging to guide definitive surgical management. Advanced techniques including 4-dimensional computed tomographic (4D-CT) scan have been investigated over the past decade. We sought to evaluate the efficacy of these emerging imaging techniques through pooled analysis of the existing evidence.
DATA SOURCES
PubMed, Embase, and Web of Science databases were queried for original English articles without any restrictions on date.
STUDY SELECTION
We included comparative observational studies but excluded animal studies, case reports, and case series. Overall, 353 abstracts were screened independently by 2 investigators along with a third reviewer to resolve conflicts. A total of 26 full-text articles were included in this review.
DATA EXTRACTION AND SYNTHESIS
This review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines. Data was independently extracted by 2 investigators and subsequently pooled into a meta-analysis using a random-effects model.
MAIN OUTCOMES AND MEASURES
Measures of imaging diagnostic performance such as sensitivity, specificity, positive predictive value, and negative predictive value were the primary outcomes of interest.
RESULTS
Overall, of 34 articles screened, 26 met criteria for qualitative synthesis, and 23 of these were appropriate for meta-analysis. Of the 26 studies included, there were 5845 patients, of which 4176 were women (79.2%). The average of mean ages reported in 23 studies was 60.9 years. Meta-analysis in all patients with PHPT revealed pooled sensitivity that was greater with 4D-CT (81%; 95% CI, 77%-84%; I2 = 88%) compared with the current first-line modality of sestamibi-single-photon emission CT (SPECT/CT) (65%; 95% CI, 59%-70%; I2 = 93%). For patients with recurrent PHPT requiring reoperation, 4D-CT pooled sensitivity was 81% (95% CI, 64%-98%; I2 = 93%) in contrast to 53% (95% CI, 35%-71%; I2 = 81%) for sestamibi-SPECT/CT. The overall quality of the 26 studies was moderate with a median (range) Methodological Index for Nonrandomized Studies score for all included studies of 15.5 (13-19).
CONCLUSIONS AND RELEVANCE
The findings of this systematic review and with meta-analyses of numerous studies from the past decade suggest that the 4D-CT can be more sensitive and specific than sestamibi-SPECT/CT in localizing PHPT. More research is needed to determine the clinical significance of this improvement in localization.
Topics: Female; Humans; Hyperparathyroidism, Primary; Male; Middle Aged; Predictive Value of Tests; Radiopharmaceuticals; Tomography, Emission-Computed, Single-Photon; Tomography, X-Ray Computed
PubMed: 35357400
DOI: 10.1001/jamaoto.2022.0271 -
Journal of Bone and Mineral Research :... Nov 2022Both medical and surgical therapy represent potential management options for patients with asymptomatic primary hyperparathyroidism (PHPT). Because uncertainty remains... (Meta-Analysis)
Meta-Analysis
The Efficacy and Safety of Medical and Surgical Therapy in Patients With Primary Hyperparathyroidism: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
Both medical and surgical therapy represent potential management options for patients with asymptomatic primary hyperparathyroidism (PHPT). Because uncertainty remains regarding both medical and surgical therapy, this systematic review addresses the efficacy and safety of medical therapy in asymptomatic patients or symptomatic patients who decline surgery and surgery in asymptomatic patients. We searched Medline, Embase, Cochrane Central Register of Controlled Trials, and PubMed from inception to December 2020, and included randomized controlled trials in patients with PHPT that compared nonsurgical management with medical therapy versus without medical therapy and surgery versus no surgery in patients with asymptomatic PHPT. For surgical complications we included observational studies. Paired reviewers addressed eligibility, assessed risk of bias, and abstracted data for patient-important outcomes. We conducted random-effects meta-analyses to pool relative risks and mean differences with 95% confidence intervals and used Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) to assess quality of evidence for each outcome. For medical therapy, 11 trials reported in 12 publications including 438 patients proved eligible: three addressed alendronate, one denosumab, three cinacalcet, two vitamin D, and two estrogen therapy. Alendronate, denosumab, vitamin D, and estrogen therapy all increased bone density. Cinacalcet probably reduced serum calcium and parathyroid hormone (PTH) levels. Cinacalcet and vitamin D may have a small or no increase in overall adverse events. Very-low-quality evidence raised the possibility of an increase in serious adverse events with alendronate and denosumab. The trials also provided low-quality evidence for increased bleeding and mastalgia with estrogen therapy. For surgery, six trials presented in 12 reports including 441 patients proved eligible. Surgery achieved biochemical cure in 96.1% (high quality). We found no convincing evidence supporting an impact of surgery on fracture, quality of life, occurrence of kidney stones, and renal function, but the evidence proved low or very low quality. Surgery was associated with an increase in bone mineral density. For patients with symptomatic and asymptomatic PHPT, who are not candidates for parathyroid surgery, cinacalcet probably reduced serum calcium and PTH levels; anti-resorptives increased bone density. For patients with asymptomatic PHPT, surgery usually achieves biochemical cure. These results can help to inform patients and clinicians regarding use of medical therapy and surgery in PHPT. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
Topics: Humans; Cinacalcet; Hyperparathyroidism, Primary; Alendronate; Calcium; Quality of Life; Denosumab; Randomized Controlled Trials as Topic; Parathyroid Hormone; Vitamin D; Estrogens
PubMed: 36053960
DOI: 10.1002/jbmr.4685 -
Frontiers in Endocrinology 2017Primary hyperparathyroidism is increasingly an asymptomatic disease at diagnosis, but the recognized guidelines for management are based on evidence obtained from... (Review)
Review
INTRODUCTION
Primary hyperparathyroidism is increasingly an asymptomatic disease at diagnosis, but the recognized guidelines for management are based on evidence obtained from studies on patients with symptomatic disease, and surgery is not always indicated. Other patients are unable to undergo surgery, and thus a medical treatment is warranted. This systematic review provides an overview of the existing literature on contemporary pharmaceutical options available for the medical management of primary hyperparathyroidism.
METHODS
Databases of medical literature were searched for articles including terms for primary hyperparathyroidism and each of the included drugs. Data on s-calcium, s-parathyroid hormone, bone turnover markers, bone mineral density (BMD) and hard endpoints were extracted and tabulated, and level of evidence was determined. Changes in s-calcium were estimated and a meta-regression analysis was performed.
RESULTS
The 1,999 articles were screened for eligibility and 54 were included in the review. Weighted mean changes calculated for each drug in s-total calcium (mean change from baseline ± SEM) were pamidronate (0.31 ± 0.034 mmol/l); alendronate (0.07 ± 0.05 mmol/l); clodronate (0.20 ± 0.040 mmol/l); mixed bisphosphonates (0.16 ± 0.049 mmol/l); and cinacalcet (0.37 ± 0.013 mmol/l). The meta-analysis revealed a significant decrease of effect on s-calcium with time for the bisphosphonates (Coef. -0.049 ± 0.023, = 0.035), while cinacalcet proved to maintain its effect on s-calcium over time. Bisphosphonates improved BMD while cinacalcet had no effect.
DISCUSSION
The included studies demonstrate advantages and drawbacks of the available pharmaceutical options that can prove helpful in the clinical setting. The great variation in how primary hyperparathyroidism is manifested requires that management should rely on an individual evaluation when counseling patients. Combining resorptive agents with calcimimetics could prove rewarding, but more studies are warranted.
PubMed: 28473803
DOI: 10.3389/fendo.2017.00079