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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 -
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 -
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 -
Surgical Oncology Sep 2021The study aim was to systematically review literature evaluating surgeon volume-outcome relationships for thyroid and parathyroid operations in order to inform surgical...
BACKGROUND
The study aim was to systematically review literature evaluating surgeon volume-outcome relationships for thyroid and parathyroid operations in order to inform surgical quality improvement initiatives. Current literature suggests surgeons who perform a high volume of thyroid and/or parathyroid operations have better outcomes than low volume surgeons, though specific volume definition are not standardized.
METHODS
Eligible studies were selected through a literature search focused on the effect of surgeon volume on thyroid and parathyroid surgery patient outcomes. The literature search was conducted in accordance with the PRISMA guidelines. Publication dates extended from January 1998 to February 2021, and were limited to articles published in English.
RESULTS
A total of 33 studies were included: 25 studies evaluating thyroid surgery outcomes, 4 studies evaluating parathyroid surgery outcomes, and 4 studies evaluating both thyroid and parathyroid (mixed) surgery outcomes. Higher volume thyroid and parathyroid surgeons were found to be associated with fewer surgical and medical complications, shorter length of hospital stay, and reduced total cost when compared to lower volume surgeons. This volume-outcome relationship was also found to specifically affect the complication and recurrence rates for thyroid cancer patients undergoing surgery, especially for individuals with advanced stage disease.
CONCLUSION
The heterogeneity in cut-offs used for characterizing surgeons as high versus low volume, and also in subsequent patient outcome measures, limited direct study comparisons. The trend of improved patient outcomes with higher surgeon volume for both thyroid and parathyroid surgeries was consistently present in all studies reviewed.
Topics: Hospitals, High-Volume; Humans; Length of Stay; Outcome Assessment, Health Care; Parathyroid Neoplasms; Parathyroidectomy; Postoperative Complications; Prognosis; Thyroid Neoplasms; Thyroidectomy
PubMed: 33915486
DOI: 10.1016/j.suronc.2021.101550 -
Cureus Jun 2023Major depressive disorder (MDD) is a common neuropsychiatry manifestation that is more prevalent lately. Many contributing factors are present (for example,... (Review)
Review
Major depressive disorder (MDD) is a common neuropsychiatry manifestation that is more prevalent lately. Many contributing factors are present (for example, neurochemical, physiological, pathophysiological, and endocrinological factors). Patients with increased serum parathyroid levels are usually linked to psychosis symptoms but not to depressive symptoms. We conducted this systematic review to explore a correlation between depressive disorder and increased serum parathyroid levels, a major endocrinological pathology, and help establish mental wellness in patients suffering from hyperparathyroidism. We conducted a thorough literature search using five major databases, MEDLINE, PubMed, PubMed Central (PMC), ScienceDirect, and Google Scholar, using three keywords-MDD, depression, and hyperparathyroidism. We included mixed method studies, including observational studies, non-randomized controlled trials, case reports, and review articles published in the last ten years, focusing on the adult and geriatric population (>18 years) and on depressive and anxiety symptoms associated with patients with hyperparathyroidism. We included 11 articles (seven observational studies + four case reports) for qualitative synthesis after screening the literature. The reviewed studies showed an association between high serum parathyroid level, high serum calcium level, high serum alkaline phosphatase level, low serum phosphorous level, and increased depressive neurocognitive symptoms. After a patient with hyperparathyroidism is treated for hypercalcemia or undergoes parathyroidectomy and the serum parathyroid levels are lowered, a decrease in severe depressive symptoms is noted. The qualitative analysis of the reviewed literature showed an association between major depressive disorder and hyperparathyroidism. This paper can guide clinicians to assess patients with increased serum parathyroid levels for depressive neuropsychiatric symptoms and plan treatment, as treatment of their hyperparathyroidism can significantly lower their depressive symptoms. More randomized controlled trials should be conducted to find the treatment effectiveness of depression in patients with hyperparathyroidism.
PubMed: 37425517
DOI: 10.7759/cureus.40150 -
Current Pharmaceutical Design 2022Some reports have pointed out that calcimimetics agents are effective in the treatment of secondary hyperparathyroidism (SHPT) in chronic kidney disease (CKD) patients,... (Meta-Analysis)
Meta-Analysis
A Systematic Review and Meta-analysis of Efficacy and Safety of Calcimimetic Agents in the Treatment of Secondary Hyperparathyroidism in Patients with Chronic Kidney Disease.
BACKGROUND
Some reports have pointed out that calcimimetics agents are effective in the treatment of secondary hyperparathyroidism (SHPT) in chronic kidney disease (CKD) patients, but there is no detailed description of the advantages and disadvantages of calcimimetics agents of SHPT in CKD patients. We tried to pool the published data to verify the effectiveness of calcimimetics agents and to compare the advantages and disadvantages of cinacalcet compared with control in the treatment of SHPT in CKD patients.
METHODS
We included eligible studies of published papers from January 1st, 2000 to December 31st, 2020 in Medline, Pubmed and Web of science databases, and the data were extracted for this meta-analysis.
RESULTS
Twenty-seven studies were eligible, and all the included studies were randomized controlled trials (RCT) including patients treated with long-term dialysis. The results indicated that calcimimetic agents can reduce the parathyroid hormone (PTH, pg/ml) level (WMD = -178.22, 95% CI: -238.57, -117.86, P < 0.00001), calcium (Ca, mg/dl) level (WMD = -0.71, 95% CI: -0.86, -0.55, P < 0.00001), phosphorus (P, mg/dl) level (WMD = -0.32, 95% CI: -0.55, -0.08, P = 0.008), calcium-phosphorus product level (WMD = -7.73, 95% CI: -9.64, -5.82, P < 0.00001). Calcimimetic agents increased the bone alkaline phosphatase (BSAP, ng/ml) levels and rate of achieving target PTH, and reduced osteocalcin levels and the rate of parathyroidectomy. Calcimimetic agents increased the total adverse events' rate, the rate of hypocalcemia and gastrointestinal side effects (nausea, vomiting, abdominal pain and diarrhea), but there was no significant difference in serious adverse events between the calcimimetic agent group and control group.
CONCLUSION
Calcimimetic agents can reduce the PTH level, Ca level, P level, calcium-phosphorus product level and do not increase serious adverse events.
Topics: Humans; Calcimimetic Agents; Calcium; Naphthalenes; Hyperparathyroidism, Secondary; Parathyroid Hormone; Renal Insufficiency, Chronic; Phosphorus; Randomized Controlled Trials as Topic
PubMed: 36305135
DOI: 10.2174/1381612829666221027110656 -
American Journal of Surgery Aug 2023We aim to evaluate the body of evidence reporting on normohormonal primary hyperparathyroidism (NHpHPT) patients to help guide their diagnosis, characterization and... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
We aim to evaluate the body of evidence reporting on normohormonal primary hyperparathyroidism (NHpHPT) patients to help guide their diagnosis, characterization and treatment.
BACKGROUND
Normohormonal primary hyperparathyroidism is a term used to describe patients with a normal PTH and elevated calcium levels. There is limited understanding regarding the presentation and appropriate management of these patients.
METHODS
A systematic review was conducted: abstract and full-text screening were independently conducted by 2 investigators. Odds ratios (OR), standard mean differences (SMD) and 95% confidence intervals were calculated.
RESULTS
Twenty-two studies were identified. Patients with NHpHPT were more likely to present with lower PTH (p < 0.00001) and calcium (p < 0.00001) levels. Intraoperatively, the NHpHPT group was 1.8 times more likely to undergo bilateral neck exploration (BNE) and harbor multigland disease. The rates of surgical cure were 93% in the NHpHPT and 96% in the pHPT groups (p = 0.0003).
CONCLUSION
Symptomatic patients with NHpHPT benefit from parathyroidectomy with prolonged intraoperative PTH monitoring, and a low threshold for conversion to BNE.
Topics: Humans; Calcium; Parathyroid Hormone; Hyperparathyroidism, Primary; Retrospective Studies; Parathyroidectomy
PubMed: 37100740
DOI: 10.1016/j.amjsurg.2023.04.004 -
Movement Disorders : Official Journal... Sep 2021The landscape of genetic forms of Parkinson's diseases (PD) has grown exponentially in recent years. Today, around 10% of PD cases are estimated to be of genetic... (Review)
Review
The landscape of genetic forms of Parkinson's diseases (PD) has grown exponentially in recent years. Today, around 10% of PD cases are estimated to be of genetic etiology. However, the link between parkinsonism or tremor and chromosome disorders, both numerical and structural, has been neglected. We reviewed the occurrence and characteristics of parkinsonism and tremor syndromes in patients with chromosomic disorders. We searched PubMed for articles published until December 2018, using the non-MESH terms "Chromosomopathy," "karyotype," "chromosome," "aneuploidy," "deletion," "inversion," "insertion," "duplication," and "Parkinson," "Parkinsonism," "Tremor," and "Parkinsonian disorder." We restricted the search to human studies and selected articles for further analysis after abstract review. Tremor syndromes in which patients had another possible clinical reason for syndromes were excluded, as well as tremor syndromes associated with point mutations, imprinting syndromes, and patients presenting with other hyperkinetic disorders. Fifty-four articles were reviewed. Aneuploidies of sex chromosomes were the most common chromosomopathy. These patients more commonly exhibited postural and kinetic tremor, often meeting the description of essential tremor. In structural chromosomopathies, the most frequent association was PD and 22q11.2 deletion syndrome, but we found case reports and case series of several additional deletion and duplication syndromes. © 2021 International Parkinson and Movement Disorder Society.
Topics: DiGeorge Syndrome; Essential Tremor; Humans; Parkinson Disease; Parkinsonian Disorders; Tremor
PubMed: 34056754
DOI: 10.1002/mds.28663 -
Head & Neck Mar 2022To evaluate the diagnostic accuracies of indocyanine green (ICG) fluorescence for identifying parathyroid glands during surgery and predicting the postoperative function. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
To evaluate the diagnostic accuracies of indocyanine green (ICG) fluorescence for identifying parathyroid glands during surgery and predicting the postoperative function.
METHODS
From six databases, 21 studies were finally included in the study. True-positive, true-negative, false-positive, and false-negative data were extracted for the analysis. The quality of each study was analyzed using the QUADAS-2 tool.
RESULTS
The sensitivity of ICG-based parathyroid gland identification was 0.9380 (95% CI [0.9003, 0.9621]). The diagnostic odds ratio for ICG-based prediction of parathyroid gland function was 54.5652 [13.2059, 225.4570]. The area under the summary receiver operating characteristic curve was 0.909. Fluorescence intensity-based prediction presented higher diagnostic accuracy than that of score-based prediction. The incidence of postoperative hypoparathyroidism was higher in the group with a zero ICG score compared to the high scored group.
CONCLUSIONS
Identification of parathyroid gland and prediction of postoperative function using ICG are valuable to patients undergoing thyroidectomy or parathyroidectomy.
Topics: Fluorescence; Humans; Hypoparathyroidism; Indocyanine Green; Parathyroid Glands; Postoperative Complications; Thyroidectomy
PubMed: 34908194
DOI: 10.1002/hed.26950 -
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