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The Cochrane Database of Systematic... Mar 2023Primary hyperparathyroidism (PHPT), a disorder in which the parathyroid glands produce excessive amounts of parathyroid hormone, is most common in older adults and... (Review)
Review
BACKGROUND
Primary hyperparathyroidism (PHPT), a disorder in which the parathyroid glands produce excessive amounts of parathyroid hormone, is most common in older adults and postmenopausal women. While most people with PHPT are asymptomatic at diagnosis, symptomatic disease can lead to hypercalcaemia, osteoporosis, renal stones, cardiovascular abnormalities and reduced quality of life. Surgical removal of abnormal parathyroid tissue (parathyroidectomy) is the only established treatment for adults with symptomatic PHPT to prevent exacerbation of symptoms and to be cured of PHPT. However, the benefits and risks of parathyroidectomy compared to simple observation or medical therapy for asymptomatic and mild PHPT are not well established.
OBJECTIVES
To evaluate the benefits and harms of parathyroidectomy in adults with PHPT compared to simple observation or medical therapy.
SEARCH METHODS
We searched CENTRAL, MEDLINE, LILACS, ClinicalTrials.gov and WHO ICTRP from their date of inception until 26 November 2021. We applied no language restrictions.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) comparing parathyroidectomy with simple observation or medical therapy for the treatment of adults with PHPT.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methods. Our primary outcomes were 1. cure of PHPT, 2. morbidity related to PHPT and 3. serious adverse events. Our secondary outcomes were 1. all-cause mortality, 2. health-related quality of life and 3. hospitalisation for hypercalcaemia, acute renal impairment or pancreatitis. We used GRADE to assess the certainty of the evidence for each outcome.
MAIN RESULTS
We identified eight eligible RCTs that included 447 adults with (mostly asymptomatic) PHPT; 223 participants were randomised to parathyroidectomy. Follow-up duration varied from six months to 24 months. Of the 223 participants (37 men) randomised to surgery, 164 were included in the analyses, of whom 163 were cured at six to 24 months (overall cure rate 99%). Parathyroidectomy compared to observation probably results in a large increase in cure rate at six to 24 months follow-up: 163/164 participants (99.4%) in the parathyroidectomy group and 0/169 participants in the observation or medical therapy group were cured of their PHPT (8 studies, 333 participants; moderate certainty). No studies explicitly reported intervention effects on morbidities related to PHPT, such as osteoporosis, osteopenia, kidney dysfunction, urolithiasis, cognitive dysfunction or cardiovascular disease, although some studies reported surrogate outcomes for osteoporosis and cardiovascular disease. A post-hoc analysis revealed that parathyroidectomy, compared to observation or medical therapy, may have little or no effect after one to two years on bone mineral density (BMD) at the lumbar spine (mean difference (MD) 0.03 g/cm,95% CI -0.05 to 0.12; 5 studies, 287 participants; very low certainty). Similarly, compared to observation, parathyroidectomy may have little or no effect on femoral neck BMD after one to two years (MD -0.01 g/cm, 95% CI -0.13 to 0.11; 3 studies, 216 participants; very low certainty). However, the evidence is very uncertain for both BMD outcomes. Furthermore, the evidence is very uncertain about the effect of parathyroidectomy on improving left ventricular ejection fraction (MD -2.38%, 95% CI -4.77 to 0.01; 3 studies, 121 participants; very low certainty). Four studies reported serious adverse events. Three of these reported zero events in both the intervention and control groups; consequently, we were unable to include data from these three studies in the pooled analysis. The evidence suggests that parathyroidectomy compared to observation may have little or no effect on serious adverse events (RR 3.35, 95% CI 0.14 to 78.60; 4 studies, 168 participants; low certainty). Only two studies reported all-cause mortality. One study could not be included in the pooled analysis as zero events were observed in both the intervention and control groups. Parathyroidectomy compared to observation may have little or no effect on all-cause mortality, but the evidence is very uncertain (RR 2.11, 95% CI 0.20 to 22.60; 2 studies, 133 participants; very low certainty). Three studies measured health-related quality of life using the 36-Item Short Form Health Survey (SF-36) and reported inconsistent differences in scores for different domains of the questionnaire between parathyroidectomy and observation. Six studies reported hospitalisations for the correction of hypercalcaemia. Two studies reported zero events in both the intervention and control groups and could not be included in the pooled analysis. Parathyroidectomy, compared to observation, may have little or no effect on hospitalisation for hypercalcaemia (RR 0.91, 95% CI 0.20 to 4.25; 6 studies, 287 participants; low certainty). There were no reported hospitalisations for renal impairment or pancreatitis.
AUTHORS' CONCLUSIONS
In accordance with the literature, our review findings suggest that parathyroidectomy, compared to simple observation or medical (etidronate) therapy, probably results in a large increase in cure rates of PHPT (with normalisation of serum calcium and parathyroid hormone levels to laboratory reference values). Parathyroidectomy, compared with observation, may have little or no effect on serious adverse events or hospitalisation for hypercalcaemia, and the evidence is very uncertain about the effect of parathyroidectomy on other short-term outcomes, such as BMD, all-cause mortality and quality of life. The high uncertainty of evidence limits the applicability of our findings to clinical practice; indeed, this systematic review provides no new insights with regard to treatment decisions for people with (asymptomatic) PHPT. In addition, the methodological limitations of the included studies, and the characteristics of the study populations (mainly comprising white women with asymptomatic PHPT), warrant caution when extrapolating the results to other populations with PHPT. Large-scale multi-national, multi-ethnic and long-term RCTs are needed to explore the potential short- and long-term benefits of parathyroidectomy compared to non-surgical treatment options with regard to osteoporosis or osteopenia, urolithiasis, hospitalisation for acute kidney injury, cardiovascular disease and quality of life.
Topics: Male; Female; Humans; Aged; Hypercalcemia; Hyperparathyroidism, Primary; Parathyroidectomy; Cardiovascular Diseases; Parathyroid Hormone; Osteoporosis; Randomized Controlled Trials as Topic
PubMed: 36883976
DOI: 10.1002/14651858.CD013035.pub2 -
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 -
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 -
Biomedicines Dec 2022Chronic kidney disease-mineral and bone disorder is one of the complications associated with chronic kidney disease. About 10-50% of patients following kidney... (Review)
Review
Chronic kidney disease-mineral and bone disorder is one of the complications associated with chronic kidney disease. About 10-50% of patients following kidney transplantation have persistent hyperparathyroidism. Hypercalcaemic hyperparathyroidism has a negative impact on the kidney transplant outcome; therefore, it requires treatment. The data regarding the treatment of persistent hyperparathyroidism provided in scientific publications are divergent and contradictory. Therefore, the aim of our systematic review was to evaluate the efficacy of persistent hyperparathyroidism treatment in patients following kidney transplantation. The Cochrane, PubMed, and Scopus databases were browsed independently by two authors. The search strategy included controlled vocabulary and keywords. The effectiveness of calcitriol, paricalcitol, cinacalcet, and parathyroidectomy was compared and analysed. The mean calcium and parathormone (PTH) concentrations per patient in the group of paricalcitol increased by 1.27% and decreased by 35.14% (n = 248); in the group of cinacalcet decreased by 12.09% and 32.16% (n = 368); and in the group of parathyroidectomy decreased by 19.06% and 86.49% (n = 15) at the end of the study compared to the baseline (n = 244, n = 342 and n = 15), respectively. Paricalcitol, cinacalcet, and parathyroidectomy decreased the intact PTH level. Cinacalcet and parathyroidectomy lowered calcium levels in renal transplant patients with hypercalcaemia. Conversely, paricalcitol increased the serum calcium concentration. Cinacalcet seems to be a good candidate in the treatment of post-transplant hyperparathyroidism.
PubMed: 36672533
DOI: 10.3390/biomedicines11010025 -
Frontiers in Endocrinology 2022Primary hyperparathyroidism is a common disorder of the parathyroid glands. Parathyroid adenoma (PA) in pregnancy is a relatively rare disease, whose diagnosis and...
OBJECTIVE
Primary hyperparathyroidism is a common disorder of the parathyroid glands. Parathyroid adenoma (PA) in pregnancy is a relatively rare disease, whose diagnosis and treatment is a challenging task. The aim of the present study is to present a new case of parathyroid adenoma during pregnancy and to give a detailed account of all reported cases of parathyroid adenoma during pregnancy in the literature.
STUDY DESIGN
A bibliographic research was performed, and characteristics of parathyroid adenomas in pregnancy such as age, gestational week at diagnosis, ionized calcium levels, genetic testing result, symptomatology, radiological method of localization, treatment method, gestational week at operation, and maternal/fetal complications were recorded.
RESULTS
A 34-year-old woman at her 25 weeks' gestation was diagnosed with parathyroid adenoma and was referred to our Surgical Department due to contraindication for conservative treatment. A parathyroidectomy was performed, and the maternal and fetal postoperative period was uneventful. Two hundred eleven cases of parathyroid adenoma in pregnancy were recorded in the literature, and statistical analysis was performed. The median gestational week at diagnosis was 21 ± 9.61 weeks. The mean level of ionized calcium was 2.69 mmol/l [SD = 0.75 (2.55-2.84 95% CI)]. Most cases were familiar (72.4%), while surgery was the preferred treatment option (67.3%). The majority of cases were asymptomatic (21.7%), and the main radiological method applied for localization was ultrasound (63.4%).
CONCLUSION
Parathyroid adenoma in pregnancy is a rare condition. The early diagnosis is of great importance as surgical treatment at the second trimester of pregnancy outweighs the maternal and fetal risks.
Topics: Humans; Female; Pregnancy; Adult; Parathyroid Neoplasms; Calcium; Adenoma; Pregnancy Complications, Neoplastic; Parathyroidectomy
PubMed: 36325457
DOI: 10.3389/fendo.2022.975954 -
World Journal of Surgery Nov 2022
Meta-Analysis
Topics: Humans; Hyperparathyroidism, Primary; Multiple Endocrine Neoplasia Type 1; Multiple Endocrine Neoplasia Type 2a; Neoplasm Recurrence, Local; Parathyroid Glands; Parathyroidectomy
PubMed: 36042033
DOI: 10.1007/s00268-022-06707-6 -
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 -
Frontiers in Endocrinology 2021We aim to assess the accuracy of near infrared autofluorescence in identifying parathyroid gland during thyroid and parathyroid surgery. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
We aim to assess the accuracy of near infrared autofluorescence in identifying parathyroid gland during thyroid and parathyroid surgery.
METHOD
A systematic literature search was conducted by using PubMed, Embase, and the Cochrane Library electronic databases for studies that were published up to February 2021. The reference lists of the retrieved articles were also reviewed. Two authors independently assessed the methodological quality and extracted the data. A random-effects model was used to calculate the combined variable. Publication bias in these studies was evaluated with the Deeks' funnel plots.
RESULT
A total of 24 studies involving 2,062 patients and 6,680 specimens were included for the meta-analysis. The overall combined sensitivity and specificity, and the area under curve of near infrared autofluorescence were 0.96, 0.96, and 0.99, respectively. Significant heterogeneities were presented (Sen: I = 87.97%, Spe: I = 65.38%). In the subgroup of thyroid surgery, the combined sensitivity and specificity, and the area under curve of near infrared autofluorescence was 0.98, 0.99, and 0.99, respectively, and the heterogeneities were moderate (Sen: I = 59.71%, Spe: I = 67.65%).
CONCLUSION
Near infrared autofluorescence is an excellent indicator for identifying parathyroid gland during thyroid and parathyroid surgery.
Topics: Animals; Humans; Optical Imaging; Parathyroid Glands; Parathyroid Neoplasms; Parathyroidectomy; Spectroscopy, Near-Infrared; Thyroid Neoplasms; Thyroidectomy
PubMed: 34234746
DOI: 10.3389/fendo.2021.701253 -
JAMA Otolaryngology-- Head & Neck... Aug 2021Accurate preoperative localization of primary hyperparathyroidism (pHPT) is an important and challenging issue for a successful parathyroidectomy. Although new imaging... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Accurate preoperative localization of primary hyperparathyroidism (pHPT) is an important and challenging issue for a successful parathyroidectomy. Although new imaging modalities have been introduced during the past decade, direct comparative studies on advanced imaging techniques are limited.
OBJECTIVE
To compare the performance of different preoperative imaging modalities for the localization of pHPT by performing a network meta-analysis (NMA).
DATA SOURCES
PubMed, Embase, and the Cochrane Library were searched from the earliest available indexing date through September 28, 2020.
STUDY SELECTION
The inclusion criteria were diagnostic tests with sensitivities of 2 or more different preoperative imaging modalities for the same indivduals.
DATA EXTRACTION AND SYNTHESIS
Two researchers independently reviewed the literature according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses extension statement of health care intervention guidelines for network meta-analyses.
MAIN OUTCOMES AND MEASURES
After classifying various imaging modalities into 8 representative imaging categories, the pooled estimation between the odds ratio and 95% credible intervals (CrIs) was calculated in the sensitivity for localization of pHPT. The surface under the cumulative ranking curve (SUCRA) values were obtained to calculate the probability of each imaging modality being the most effective diagnostic method.
RESULTS
A total of 8495 patients from 119 direct comparative studies using 2 or more imaging modalities for localization of pHPT were included. The sensitivity of choline positron emission tomography and computed tomography (PET-CT) was significantly higher than that of technetium 99m sestamibi single-photon emission computed tomography (MIBI SPECT) in both patient-based and lesion-based analyses (patient-based analysis: odds ratio, 5.22; 95% CrI, 2.36-11.80; lesion-based analysis: odds ratio, 17.70; 95% CrI, 5.79-60.10). Among 8 representative imaging modality categories, choline PET-CT showed the highest SUCRA value in both patient-based and lesion-based analyses. In patient-based analysis after 2010, choline PET-CT showed the highest SUCRA value, followed by the CT category, although MIBI SPECT had the highest SUCRA value in analysis before 2009.
CONCLUSIONS AND RELEVANCE
The results from this network meta-analysis suggest that choline PET-CT showed the best performance in both patient-based and lesion-based analyses and that choline PET-CT would be the best preoperative imaging modality for localization of pHPT.
Topics: Diagnostic Imaging; Humans; Hyperparathyroidism, Primary; Preoperative Care
PubMed: 34081083
DOI: 10.1001/jamaoto.2021.0915 -
The Journal of International Medical... Mar 2021A meta-analysis to investigate the risk factors for postoperative hypocalcaemia after thyroidectomy in adult patients. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
A meta-analysis to investigate the risk factors for postoperative hypocalcaemia after thyroidectomy in adult patients.
METHODS
A systematic search of publications in the electronic databases (PubMed®, The Cochrane Library, Web of Science, OVID and Embase®) from inception to June 2020 was conducted. Screening of titles, abstracts and full texts and data extraction were independently performed by two authors. The OR was selected as the pooled estimate.
RESULTS
The analysis included 23 studies. Twelve significant risk factors for postoperative hypocalcaemia were identified: hypoparathyroidism, OR 5.58; total thyroidectomy, OR 3.59; hypomagnesaemia, OR 2.85; preoperative vitamin D deficiency, OR 2.32; female sex, OR 1.49; thyroid malignancy, OR 1.85; thyroiditis, OR 1.48; substernal multinodular goitres, OR 1.70; parathyroidectomy, OR 1.58; central compartment neck dissection, OR 1.17; modified radical neck dissection, OR 1.57; and central neck dissection, OR 1.54.
CONCLUSIONS
This meta-analysis provides moderate-to-high quality evidence that the 12 risk factors were predictive of postoperative hypocalcaemia, which should be monitored closely before thyroidectomy.
Topics: Adult; Female; Humans; Hypocalcemia; Hypoparathyroidism; Neck Dissection; Postoperative Complications; Risk Factors; Thyroidectomy
PubMed: 33779362
DOI: 10.1177/0300060521996911