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American Journal of Kidney Diseases :... Nov 2023Vitamin D is widely used to manage chronic kidney disease-mineral and bone disorder (CKD-MBD). We evaluated the effects of vitamin D therapy on mortality,...
RATIONALE & OBJECTIVE
Vitamin D is widely used to manage chronic kidney disease-mineral and bone disorder (CKD-MBD). We evaluated the effects of vitamin D therapy on mortality, cardiovascular, bone, and kidney outcomes in adults with CKD.
STUDY DESIGN
Systematic review of randomized controlled trials (RCT) with highly sensitive searching of MEDLINE, Embase, and CENTRAL, through February 25, 2023.
SETTING & STUDY POPULATIONS
Adults with stage 3, 4, or 5 CKD, including kidney failure treated with dialysis. Recipients of a kidney transplant were excluded.
SELECTION CRITERIA FOR STUDIES
RCTs with≥3 months of follow-up evaluating a vitamin D compound.
DATA EXTRACTION
Data were extracted independently by three investigators.
ANALYTICAL APPROACH
Treatment estimates were summarized using random effects meta-analysis. Primary review endpoints were all-cause death, cardiovascular death, and fracture. Secondary outcomes were major adverse cardiovascular events, hospitalization, bone mineral density, parathyroidectomy, progression to kidney failure, proteinuria, estimated glomerular filtration rate, hypercalcemia, hyperphosphatemia, biochemical markers of CKD-MBD, and various intermediate outcome measures of cardiovascular disease. Risk of bias was assessed using the Cochrane Risk of Bias (RoB) 2 tool. Evidence certainty was adjudicated using GRADE.
RESULTS
Overall, 128 studies involving 11,270 participants were included. Compared with placebo, vitamin D therapy probably had no effect on all-cause death (relative risk [RR], 1.04; 95% CI, 0.84-1.24); and uncertain effects on fracture (RR, 0.68; 95% CI, 0.37-1.23) and cardiovascular death (RR, 0.73; 95% CI, 0.31-1.71). Compared with placebo, vitamin D therapy lowered serum parathyroid hormone and alkaline phosphatase, but increased serum calcium.
LIMITATIONS
Data were limited by trials with short-term follow-up periods, small sample size, and the suboptimal quality.
CONCLUSIONS
Vitamin D therapy did not reduce the risk of all-cause death in people with CKD. Effects on fracture and cardiovascular and kidney outcomes were uncertain.
TRIAL REGISTRATION
Registered at PROSPERO with study number CRD42017057691.
PLAIN-LANGUAGE SUMMARY
Chronic kidney disease (CKD) is associated with increased risk of death, cardiovascular disease, and fractures. This excess risk is thought to be related to changes in bone and mineral metabolism, leading to the development of CKD-mineral and bone disorder (CKD-MBD) which is characterized by vascular calcification and reduced bone quality. Vitamin D is commonly used in the treatment of this condition. We reviewed randomized controlled trials examining the effect of vitamin D therapy in CKD. We found that vitamin D therapy affects serum biomarkers, including an increase in serum calcium. However, it probably has no effect on risk of all-cause death in CKD, and the effects on other clinical bone, cardiovascular, and kidney outcomes are uncertain.
PubMed: 37356648
DOI: 10.1053/j.ajkd.2023.04.003 -
American Journal of Otolaryngology 2017Analyze the efficacy and indications for parathyroidectomy as an intervention for tertiary hyperparathyroidism. (Review)
Review
OBJECTIVE
Analyze the efficacy and indications for parathyroidectomy as an intervention for tertiary hyperparathyroidism.
DATA SOURCES
PubMed, MEDLINE, and Cochrane Library databases.
REVIEW METHODS
A systematic literature search was performed using the. Original research articles in English were retrieved using the search terms ("tertiary hyperparathyroidism" OR "3HPT") AND "parathyroidectomy". Articles were analyzed in regards to their surgical indications, operative endpoints, comparison between different surgical interventions, characterization of disease recurrence rates, and evaluation of alternative medical management.
RESULTS
Thirty studies met the criteria for inclusion. Among the studies that report indications for parathyroidectomy, persistent hypercalcemia as well as clinical manifestations of hypercalcemia despite medical therapy predicted which patients would eventually need surgical intervention. The majority of studies comparing the extent of parathyroidectomy recommended a more focused approach to parathyroidectomy when warranted. All studies found that parathyroidectomy was an effective treatment for 3HPT. Three studies discussed alternative conservative approaches.
CONCLUSION
Interestingly, hyperparathyroidism alone is not an indication for surgery without other findings; rather, symptomatic hypercalcemia appears to be the main indication. Most studies recommend limited or subtotal parathyroidectomy for 3HPT. The operative endpoint of surgery is not necessarily a return of PTH to normal, but a >50% drop in PTH level even if PTH remains above normal. Additionally, "success" or "cure" is defined as normal calcium levels regardless of whether or not PTH is elevated. It appears the goal of surgery for 3HPT is not a normal PTH value, but a normal calcium level at least six months postoperatively.
Topics: Humans; Hyperparathyroidism; Parathyroidectomy
PubMed: 28735762
DOI: 10.1016/j.amjoto.2017.06.009 -
Otolaryngology--head and Neck Surgery :... Jul 2024Currently, the relationship between parathyroidectomy and objective neuropsychiatric outcomes are not clearly defined. The purpose of this study is to perform the first... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Currently, the relationship between parathyroidectomy and objective neuropsychiatric outcomes are not clearly defined. The purpose of this study is to perform the first ever Meta-analysis of preoperative and postoperative PHQ-9 and GAD-7 scores in patients with primary hyperparathyroidism undergoing parathyroidectomy with the goal of identifying a specific psychometric score that could be used as an indication for surgical intervention.
DATA SOURCES
A comprehensive search of the literature was performed using PubMed, Embase, PsycINFO, Web of Science, and Ovid All EBM Reviews.
REVIEW METHODS
Studies met inclusion criteria if they evaluated preoperative and postoperative PHQ-9 and/or GAD-7 scores in patients with primary hyperparathyroidism undergoing parathyroidectomy. Random effects Meta-analyses were used to analyze the compiled data.
RESULTS
The literature search returned 1433 articles for initial review of which 6 (1105 participants) met criteria for inclusion and Meta-analysis. Meta-analysis revealed that primary hyperparathyroidism patients had significantly higher presurgical PHQ-9 scores when compared to control groups. Additionally, patients experienced a statistically significant and sustained decrease in PHQ-9 scores following parathyroidectomy. Notably, there was a dramatic decrease in the percentage of patients with PHQ-9 scores ≥10 (considered clinically significant for depression) following parathyroidectomy.
CONCLUSION
Patients with primary hyperparathyroidism experience a statistically significant and sustained improvement in PHQ-9 scores following parathyroidectomy. Additionally, symptoms of anxiety and suicidal ideation appear to decrease after parathyroidectomy. We propose that a PHQ-9 score ≥10 could potentially be used as an indication for parathyroidectomy in patients with asymptomatic primary hyperparathyroidism.
Topics: Parathyroidectomy; Humans; Hyperparathyroidism, Primary; Psychometrics; Depression; Anxiety
PubMed: 38415869
DOI: 10.1002/ohn.698 -
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 -
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 -
Journal of Robotic Surgery Dec 2020Minimal invasive techniques in endocrine surgery were lately adopted by surgical teams due to significant complications related to inadequate operative space and high... (Review)
Review
Minimal invasive techniques in endocrine surgery were lately adopted by surgical teams due to significant complications related to inadequate operative space and high risk of injuring crucial surrounding structures, such as vessels and nerves. Over the last years, technological improvements introduced robotic systems and approaches in endocrine surgery. Several case reports and series have described the safety and efficacy of these procedures such as robotic thyroidectomy and robotic parathyroidectomy. In the current review, we included 15 studies which described robotic-assisted parathyroidectomy for cervical parathyroid adenoma, in patients diagnosed with primary hyperparathyroidism or secondary hyperparathyroidism. No significant negative short-term outcomes were observed, in terms of postoperative complications, such as temporary or permanent injury of RLN, postoperative hypoparathyroidism and blood loss. The cosmetic result was, definitely, superior in comparison to conventional open parathyroidectomy. Despite the fact that RAP is an effective and curative method for patients with PHPT or secondary hyperparathyroidism, there are no available randomized clinical trials to establish this modern procedure as a gold-standard treatment strategy for these patients.
Topics: Adenoma; Female; Humans; Hyperparathyroidism, Primary; Hyperparathyroidism, Secondary; Male; Parathyroid Neoplasms; Parathyroidectomy; Robotic Surgical Procedures; Treatment Outcome
PubMed: 32661866
DOI: 10.1007/s11701-020-01119-x -
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 -
In Vivo (Athens, Greece) 2016This article reviews epidemiology, risk factors and treatment modalities of postsurgical hypoparathyroidism (PHypo). PHypo occurs after total thyroidectomy due to injury... (Review)
Review
This article reviews epidemiology, risk factors and treatment modalities of postsurgical hypoparathyroidism (PHypo). PHypo occurs after total thyroidectomy due to injury of parathyroid glands and/or their blood supply or after parathyroidectomy. PHypo results in hypocalcemia because parathyroid hormone (PTH) secretion is impaired and cannot mobilize calcium from bone, reabsorb calcium from the distal nephron and stimulate renal 1α-hydroxylase activity. It usually appears in the first days after surgery and it can be symptomatic or asymptomatic. Risk factors are low level of intraoperative PTH and presence of parathyroid gland in the pathological specimen. Patients usually present with paresthesia, cramps or tetany, but the disorder may also manifest acutely with seizures, bronchospasm, laryngospasm or cardiac rhythm disturbances. Standard treatment is vitamin D analogues and calcium supplementation.
Topics: Calcium; Humans; Hypoparathyroidism; Parathyroid Glands; Parathyroid Hormone; Parathyroidectomy; Postoperative Complications; Thyroidectomy; Vitamin D; Vitamins
PubMed: 27107072
DOI: No ID Found -
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 -
Renal Failure Nov 2017Total parathyroidectomy (tPTX) and total parathyroidectomy with autotransplantation (tPTX + AT) are effective and inexpensive treatments for secondary... (Comparative Study)
Comparative Study Meta-Analysis Review
BACKGROUND
Total parathyroidectomy (tPTX) and total parathyroidectomy with autotransplantation (tPTX + AT) are effective and inexpensive treatments for secondary hyperparathyroidism (sHPT), but we do not know which one is the optimal approach. Therefore, we undertook a meta-analysis to compare the safety and efficacy of these two surgical procedures.
METHODOLOGY
Studies published in English on PubMed, Embase and the Cochrane Library from inception to 27 September 2016 were searched systematically. Eligible studies comparing tPTX with tPTX + AT for sHPT were included and Review Manager v5.3 was used.
RESULTS
Eleven studies were included in this meta-analysis. Ten cohort studies and one randomized controlled trial (RCT) involving 1108 patients with sHPT were identified. There was no significant difference in the prevalence of surgical complications (relative risk [RR], 1.71; 95% confidence interval [CI], 0.77-3.79; p = .19), all-cause mortality (RR, 0.68; 95% CI, 0.33-1.39; p = .29), sHPT persistence (RR, 3.81; 95% CI, 0.56-25.95; p = .17) or symptomatic improvement (RR, 1.02; 95% CI, 0.91-1.13; p = .79). tPTX could reduce the risk of sHPT recurrence (RR, 0.19; 95% CI, 0.09-0.41; p < .0001) and reoperation because of recurrence or persistence of sHPT (RR, 0.46; 95% CI 0.24-0.86; p = .01) compared with tPTX + AT. Simultaneously, tPTX increased the risk of hypoparathyroidism (RR, 2.63; 95% CI, 1.06-6.51; p = .04).
CONCLUSIONS
We found tPTX and tPTX + AT to be useful methods for sHPT treatment. tPTX was superior for reducing the risk of sHPT recurrence and reoperation than tPTX + AT but, due to a lack of high statistical-power RCTs, comparative studies will be needed in the future.
Topics: Humans; Hyperparathyroidism, Secondary; Parathyroidectomy; Reoperation; Transplantation, Autologous
PubMed: 28853301
DOI: 10.1080/0886022X.2017.1363779