-
American Journal of Kidney Diseases :... Sep 2020Comparative benefits and harms of calcimimetic agents used for the treatment of secondary hyperparathyroidism have not been well characterized. We sought to compare the... (Comparative Study)
Comparative Study Meta-Analysis
RATIONALE & OBJECTIVE
Comparative benefits and harms of calcimimetic agents used for the treatment of secondary hyperparathyroidism have not been well characterized. We sought to compare the effectiveness of 3 calcimimetic agents using published data.
STUDY DESIGN
Systematic review of randomized controlled trials and network meta-analysis.
SETTING & STUDY POPULATION
Adults with chronic kidney disease enrolled in a clinical trial of a calcimetic agent.
SEARCH STRATEGY & SOURCES
MEDLINE, EMBASE, CENTRAL (from February 7, 2013, to November 21, 2019), and a published meta-analysis.
DATA EXTRACTION
Two reviewers independently extracted the study data, assessed risk of bias, and rated evidence certainty using Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria.
ANALYTICAL APPROACH
Frequentist network meta-analysis was conducted. The primary review outcomes were achievement of a target reduction in serum parathyroid hormone (PTH) levels and hypocalcemia. Additional outcomes were nausea, vomiting, serious adverse events, all-cause mortality, cardiovascular mortality, heart failure, and fracture.
RESULTS
36 trials (11,247 participants) were included. All except 4 trials involved dialysis patients. Median follow-up was 26 weeks (range, 1 week to 21.2 months). Compared with placebo, calcimimetic agents had higher odds of achieving target PTH levels with high or moderate certainty. Etelcalcetide had the highest odds of achieving a PTH target compared with evocalcet (OR, 4.93; 95% CI, 1.33-18.2) and cinacalcet (OR, 2.78; 95% CI, 1.19-6.67). Etelcalcetide appeared to cause more hypocalcemia than cinacalcet and evocalcet. Cinacalcet and to a lesser extent etelcalcetide appeared to cause more nausea than placebo. Differences in risk for mortality, cardiovascular end points, or fractures across calcimimetic agents could not be discerned with sufficient certainty.
LIMITATIONS
Lack of longer-term data; heterogeneous end point definitions.
CONCLUSIONS
Evidence of the benefits of calcimimetic therapy is limited to short-term assessment of a putative surrogate outcome (serum PTH). Although etelcalcetide was associated with the largest reduction in PTH levels, side-effect profiles differed across the 3 calcimimetic agents, making it not possible to identify 1 preferred agent.
Topics: Adult; Calcimimetic Agents; Calcium; Cardiovascular Diseases; Cinacalcet; Comorbidity; Female; Fractures, Bone; Heart Failure; Humans; Hyperparathyroidism, Secondary; Male; Mortality; Naphthalenes; Nausea; Parathyroid Hormone; Peptides; Pyrrolidines; Randomized Controlled Trials as Topic; Renal Dialysis; Renal Insufficiency, Chronic; Treatment Outcome; Vomiting
PubMed: 32475604
DOI: 10.1053/j.ajkd.2020.02.439 -
The Surgeon : Journal of the Royal... Dec 2021Parathyroid cancers are rare and difficult to distinguish from benign parathyroid tumours. Prediction of malignancy often relies on intraoperative assessment of... (Review)
Review
INTRODUCTION
Parathyroid cancers are rare and difficult to distinguish from benign parathyroid tumours. Prediction of malignancy often relies on intraoperative assessment of invasion. Standard histology is also inadequate; especially in the absence of local invasion, lymph nodal disease and metastasis. The aim of this project was to systematically review published literature on potential bio-markers used for the diagnosis of parathyroid cancer.
METHODS
Pubmed, Web of Science and Medline databases were searched. Inclusion criteria included English language papers published after 1985 and reporting on biomarkers in human studies of parathyroid cancer and benign disease.
RESULTS
118 relevant papers were appraised; all were observational studies. At least 2 papers studied 8 serum, 4 urine and 27 tissue biomarkers on the diagnosis of parathyroid cancer. Of these, 5 serum and 13 tissue markers have been demonstrated in at least one study to be statistically different in benign and malignant disease. We present a synthesis of data for each biomarker and measures of diagnostic accuracy where possible.
CONCLUSIONS
Consideration should be given to the use of a panel of biomarkers to review patients with suspected parathyroid cancer. A profile including serum calcium and PTH levels and tissue expression of APC, Parafibromin, PGP9.5, Galectin 3 and Ki67 is proposed. Systematic Review Registration Number - CRD42019127833.
Topics: Biomarkers; Biomarkers, Tumor; Humans; Immunohistochemistry; Parathyroid Neoplasms; Precancerous Conditions; Tumor Suppressor Proteins
PubMed: 33642204
DOI: 10.1016/j.surge.2021.01.011 -
World Journal of Surgery Nov 2022Multiple endocrine neoplasia type 1 (MEN1)-associated primary hyperparathyroidism (pHPT) is classically associated with an asymmetric and asynchronous parathyroid... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Multiple endocrine neoplasia type 1 (MEN1)-associated primary hyperparathyroidism (pHPT) is classically associated with an asymmetric and asynchronous parathyroid involvement. Subtotal parathyroidectomy (STP), which is currently the recommended surgical treatment, carries a high risk of permanent hypoparathyroidism. The results of less than subtotal parathyroidectomy (LSTP) are conflicting, and its place in this setting is still a matter of debate. The aim of this study was to identify the place of LSTP in the surgical management of patients with MEN-associated pHPT.
METHODS
A systematic literature review was conducted in accordance with PRISMA and MOOSE guidelines, for studies comparing STP and LSTP for MEN1-associated pHPT. The results of the two techniques, regarding permanent hypoparathyroidism, persistent hyperparathyroidism and recurrent hyperparathyroidism were computed using pairwise random-effect meta-analysis.
RESULTS
Twenty-five studies comparing STP and LSTP qualified for inclusion in the quantitative synthesis. In total, 947 patients with MEN1-associated pHPT were allocated to STP (n = 569) or LSTP (n = 378). LSTP reduces the risk of permanent hypoparathyroidism [odds ratio (OR) 0.29, confidence interval (CI) 95% 0.17-0.49)], but exposes to higher rates of persistent hyperparathyroidism [OR 4.60, 95% CI 2.66-7.97]. Rates of recurrent hyperparathyroidism were not significantly different between the two groups [OR 1.26, CI 95% 0.83-1.91].
CONCLUSIONS
LSTP should not be abandoned and should be considered as a suitable surgical option for selected patients with MEN1-associated pHPT. The increased risk of persistent hyperparathyroidism could improve with the emergence of more efficient preoperative localization imaging techniques and a more adequate patients selection.
Topics: Humans; Hyperparathyroidism, Primary; Hypoparathyroidism; Multiple Endocrine Neoplasia Type 1; Parathyroid Glands; Parathyroidectomy
PubMed: 35767091
DOI: 10.1007/s00268-022-06633-7 -
Frontiers in Oncology 2022Parathyroid carcinoma (PC) is an extremely rare malignant tumor with an incidence of about 6 new cases per 10 million inhabitants per year. While several papers have...
BACKGROUND
Parathyroid carcinoma (PC) is an extremely rare malignant tumor with an incidence of about 6 new cases per 10 million inhabitants per year. While several papers have been published on treatments and outcomes of PC patients with loco-regional disease, little is known about the prognosis, treatment strategies, and prognostic factors of patients with distant metastasis.
MATERIALS AND METHODS
We performed a systematic review and a pooled analysis of histopathologically confirmed PC cases published in literature using the following keywords: "metastasis-metastatic-secondary nodes" AND "parathyroid carcinoma". Original case reports and case series reporting metastatic parathyroid carcinoma were included. Data from 58 articles were extracted in a piloted form by five reviewers on a shared database.
RESULTS
Seventy-nine patients with metastatic PC were identified between 1898 and 2018. Ten (13%) patients had synchronous metastases, while metachronous metastases occurred in 43 (54%) patients. The remaining 26 patients developed metastatic disease concomitantly to local recurrence. Primary hyperparathyroidism guided the diagnosis of metastatic recurrence in 58 (73%) patients. Surgery was the main primary approach adopted, as it was performed in 43 (54%) patients. Twenty (25%) patients underwent systemic antineoplastic therapy, consisting of chemotherapy, immunotherapy, tyrosine kinase inhibitors, and hexestrol therapy. Bone resorption inhibitors had a limited efficacy in the long-term control of hypercalcemia. After a median follow-up of 37.5 months, 43 (55%) patients died, 22 (51%) due to the consequences of uncontrolled PHPT. The median overall survival was 36 months (range: 1-252). Surgery was associated with a better OS (HR 0.48, 95% CI 0.26-0.88), whereas bone metastases represented a negative prognostic factor (HR 2.7, 95% CI 1.4-5.2).
CONCLUSION
Metastatic PC has a relatively poor prognosis. The main goals of treatment are to counteract tumor growth and control hypercalcemia. Surgery of metastases is the best approach to achieve rapid control of PHPT and longer survival. Target therapies and immunotherapy deserve to be extensively tested in metastatic PC and strategies to better control hypercalcemia should be implemented.
PubMed: 36226055
DOI: 10.3389/fonc.2022.997009 -
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 -
JAMA Surgery Sep 2022Definitive treatment of primary hyperparathyroidism (pHPT) with curative parathyroidectomy has been shown to improve nonspecific neurocognitive symptoms and may improve...
IMPORTANCE
Definitive treatment of primary hyperparathyroidism (pHPT) with curative parathyroidectomy has been shown to improve nonspecific neurocognitive symptoms and may improve long-term quality of life (QOL). However, QOL is not currently routinely assessed preoperatively, and as a result, diminished QOL may be overlooked as an indication for surgery.
OBJECTIVE
To examine results for measures of long-term QOL after parathyroidectomy in patients with pHPT.
EVIDENCE REVIEW
A systematic, English-language literature review was performed to assess the long-term association of parathyroidectomy, defined as a minimum of 1-year postoperative follow-up, with QOL in patients with pHPT. We conducted a search of PubMed and Scopus using Medical Subject Heading (MeSH) terms for hyperparathyroidism, parathyroid hormone, parathyroidectomy, hypercalcemia, and quality of life. All relevant literature published between June 1998 and February 15, 2021, was included. Study selection was guided by the Preferred Reporting Items for Systematic Review and Meta-analyses (PRISMA) strategy.
FINDINGS
Thirty-one studies conducted in 14 countries with a minimum of 1 year of follow-up were included, comprising 3298 patients with pHPT (2975 underwent parathyroidectomy; 323 were observed), 5445 age- and sex-matched control participants, and 386 control patients with benign thyroid disease. To assess QOL, 21 studies (68%) used a general tool, the 36-item Short Form Survey (SF-36), and 8 (26%) used the disease-specific tool Parathyroidectomy Assessment of Symptoms (PAS). The remaining studies used a combination of 10 additional QOL tools. The median follow-up period was 1 year (range, 1-10 years). Of the 31 studies, 27 (87%) demonstrated significant score improvement in long-term QOL after parathyroidectomy, including 1 study that showed continued improvement in QOL 10 years after parathyroidectomy. The remaining 4 studies (13%) reported mixed results.
CONCLUSIONS AND RELEVANCE
This systematic review suggests that parathyroidectomy is associated with improved and sustained QOL in patients with pHPT. Patients with pHPT should be screened with a validated QOL tool such as the SF-36 or PAS at the time of diagnosis to guide discussion of these symptoms in the preoperative setting and the potential for long-term improvement after curative parathyroidectomy.
PubMed: 36103163
DOI: 10.1001/jamasurg.2022.4249 -
International Journal of Hyperthermia :... 2021Microwave ablation (MWA) is used for the treatment of severe secondary hyperparathyroidism (SHPT), but its efficacy and safety still remained unclear. This study aimed... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Microwave ablation (MWA) is used for the treatment of severe secondary hyperparathyroidism (SHPT), but its efficacy and safety still remained unclear. This study aimed to investigate the efficacy and safety of ultrasound (US)-guided MWA in patients with SHPT.
METHODS
The PubMed, Cochrane library, Embase, China national knowledge infrastructure (CNKI) and Wanfang databases were searched to identify published studies that evaluated the efficacy and safety of US-guided MWA in patients with SHPT. The primary outcomes were parathyroid hormone (PTH), serum calcium and phosphorus levels.
RESULTS
A total of 26 studies with 932 patients were identified. The PTH levels showed significant reduction at 1 month [weighted mean difference (WMD) = 945.33, 95% CI: 797.15∼1093.52] and 6 months (WMD = 1,151.91, 95% CI: 990.93∼1312.89) after MWA of SHPT patients. The serum calcium (WMD = 0.39, 95% CI: 0.30 ∼ 0.48) and phosphorus levels (WMD = 0.64, 95% CI: 0.43 ∼ 0.85) showed significant reduction at 6 months after MWA of SHPT patients. The most common complications observed were hypocalcemia (35.2%) and transient hoarseness (9.2%). No other major complications or death occurred in our study patients.
CONCLUSION
These findings suggest MWA as a safe and effective minimally invasive technique for the management of SHPT. PTH, calcium, and phosphorus levels were significantly reduced at 1 and 6 months after MWA.
Topics: Ablation Techniques; Humans; Hyperparathyroidism, Secondary; Microwaves; Parathyroid Hormone; Ultrasonography, Interventional
PubMed: 34428994
DOI: 10.1080/02656736.2021.1965664 -
Health and Quality of Life Outcomes Apr 2024The quality of patient-reported outcome measures (PROMs) used to assess the outcomes of primary hyperparathyroidism (PHPT), a common endocrine disorder that can... (Review)
Review
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.
Topics: Adult; Humans; Quality of Life; Reproducibility of Results; Hyperparathyroidism, Primary; Patient Reported Outcome Measures; Consensus
PubMed: 38566079
DOI: 10.1186/s12955-024-02248-9 -
The Laryngoscope Aug 2021The primary objective of this study was to assess the safety of parathyroidectomy during pregnancy as treatment for hyperparathyroidism (HPTH) in comparison to...
OBJECTIVES/HYPOTHESIS
The primary objective of this study was to assess the safety of parathyroidectomy during pregnancy as treatment for hyperparathyroidism (HPTH) in comparison to nonsurgical management plans. Secondary outcomes involved analyzing the safety of surgery in the third trimester and the benefit of operating on asymptomatic pregnant patients.
STUDY DESIGN
Systematic review.
METHODS
PRISMA-guided systematic review of all cases of primary hyperparathyroidism during pregnancy published in peer-reviewed English journals on PubMed/MEDLINE, EMBASE, and SCOPUS from 1980 to 2020.
RESULTS
A total of 75 manuscripts were included in this review describing 382 cases of gestational hyperparathyroidism. The median maternal age was 31 years. Overall, 108 cases (28.3%) underwent parathyroidectomy during pregnancy while 274 cases (71.7%) were treated nonsurgically. The majority of surgeries took place during the second trimester (67.6%). Complications and/or deaths were less likely to occur after surgery in the second trimester (4.48%) as compared to surgery in the third trimester (21.1%). Nine surgically treated cases resulted in infant complications and/or death; however, none of these nine cases had any surgical complications. Despite these complications, the overall infant complication rate for patients who underwent surgical treatment remained lower than that of patients treated with conservative therapy (9.1% vs. 38.9%).
CONCLUSIONS
This review suggests that for all pregnant patients with diagnosed HPTH, parathyroidectomy should be considered regardless of symptomatology. Our data suggest that parathyroidectomy is associated with fewer risks than more conservative treatments and results in better fetal outcomes. Surgery during the third trimester is feasible and surgery should be considered in both symptomatic and asymptomatic patients. Laryngoscope, 131:1915-1921, 2021.
Topics: Adult; Conservative Treatment; Female; Humans; Hyperparathyroidism, Primary; Parathyroidectomy; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Pregnancy Trimester, Third; Treatment Outcome
PubMed: 33751589
DOI: 10.1002/lary.29489 -
International Journal of Surgery... Aug 2021Primary hyperparathyroidism (PHPT) is a common endocrine disorder. In the last few decades, the introduction of Rapid Intraoperative Parathyroid Hormone (ioPTH)... (Meta-Analysis)
Meta-Analysis Review
The role of Rapid Intraoperative Parathyroid Hormone (ioPTH) assay in determining outcome of parathyroidectomy in primary hyperparathyroidism: A systematic review and meta-analysis.
BACKGROUND
Primary hyperparathyroidism (PHPT) is a common endocrine disorder. In the last few decades, the introduction of Rapid Intraoperative Parathyroid Hormone (ioPTH) monitoring has allowed to ensurance of the excision of all hyperfunctioning parathyroid tissues, reducing the risks of persistent and recurrent PHPT. However, the use of ioPTH is still debated among endocrine surgeons.
MATERIAL AND METHODS
The objective of this systematic review and meta-analysis was to assess if ioPTH monitoring is able to reduce the incidence of persistent or recurrent PHPT. A systematic literature search was performed using PubMed, Scopus, ISI-Web of Science and Cochrane Library Database. Prospective and retrospective studies addressing the efficacy of ioPTH monitoring were included in the systematic review and meta-analysis. The random-effects model was assumed to account for different sources of variation among studies. The overall effect size was computed through the inverse variance method. Heterogeneity across studies, possible outlier studies, and publication bias were evaluated.
RESULTS
A total of 28 studies with 13,323 patients were included in the quantitative analysis. The incidence of operative failure was 3.2% in the case group and 5.8% in the control group. After excluding three outlier studies, the quantitative analysis revealed that ioPTH reduced significantly the incidence of postoperative persistent or recurrent PHPT. (Risk Difference = -0.02; CI = -0.03, -0.01; p < 0.001). There was no evidence of heterogeneity among the studies (Q = 19.92, p = 0.70; I = 0%). The analysis of several continuous moderators revealed that the effectiveness of ioPTH was larger in studies with lower preoperative serum calcium values and higher incidences of multiple gland disease.
CONCLUSION
ioPTH monitoring is effective in reducing the incidence of persistent and recurrent PHPT. Its routine use should be suggested in the next guidelines regarding management of PHPT.
Topics: Humans; Hyperparathyroidism, Primary; Intraoperative Period; Parathyroid Hormone; Parathyroidectomy; Secondary Prevention; Treatment Outcome
PubMed: 34339883
DOI: 10.1016/j.ijsu.2021.106042