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The Journal of Clinical Endocrinology... May 2021Current data about the cardiovascular manifestations of mild primary hyperparathyroidism (pHPT) are often conflicting. Pulse wave velocity (PWV) is the gold standard for... (Meta-Analysis)
Meta-Analysis
CONTEXT
Current data about the cardiovascular manifestations of mild primary hyperparathyroidism (pHPT) are often conflicting. Pulse wave velocity (PWV) is the gold standard for assessing aortic stiffness, and it predicts cardiovascular morbidity and mortality.
OBJECTIVE
Primary outcomes were to investigate if mild pHPT was associated with higher PWV and if parathyroidectomy (PTX) reduced PWV in mild pHPT. Secondary outcome was to investigate blood pressure changes after PTX.
METHODS
Sources were PubMed, Google Scholar, SCOPUS, Web of Science, and the Cochrane Library. Eligible studies included reports of PWV in patients with mild pHPT and controls, or in patients with mild pHPT before and after PTX. Two investigators independently identified eligible studies and extracted data. Pooled mean difference (MD) was the summary effect measure. Data were presented in forest plots with outlier and influential case diagnostics. Nine observational studies and one randomized clinical trial were selected, including 433 patients with mild pHPT, 171 of whom underwent PTX, and 407 controls. PWV was significantly higher in mild pHPT than in controls (MD = 1.18, 0.67 to 1.68, P < .0001). Seven studies evaluated the effect of PTX on PWV. PTX significantly reduced PWV (MD = -0.48, -0.88 to -0.07, P = .022).
CONCLUSION
Aortic stiffness is increased in patients with mild pHPT, supporting the notion that mild pHPT is also associated with adverse cardiovascular manifestations. PTX significantly reduced arterial stiffness in mild pHPT, indicating that the benefit of PTX over cardiovascular manifestations should not be dismissed but it deserves further studies.
Topics: Aged; Female; Humans; Hyperparathyroidism, Primary; Male; Middle Aged; Parathyroid Hormone; Parathyroidectomy; Pulse Wave Analysis; Severity of Illness Index; Vascular Stiffness
PubMed: 33693666
DOI: 10.1210/clinem/dgab157 -
JAMA Otolaryngology-- Head & Neck... Feb 2021Intraoperative parathyroid hormone (ioPTH) is a surgical adjunct that has been increasingly used during minimally invasive parathyroidectomy (MIP). Despite its growing... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Intraoperative parathyroid hormone (ioPTH) is a surgical adjunct that has been increasingly used during minimally invasive parathyroidectomy (MIP). Despite its growing popularity, to our knowledge a meta-analysis comparing MIP with ioPTH vs MIP without ioPTH has not yet been conducted.
OBJECTIVE
To evaluate the safety and efficacy of MIP with ioPTH for treatment of primary hyperparathyroidism.
DATA SOURCES
A systematic search of the databases PubMed, Embase, Scopus, Web of Science, and Cochrane Collaboration was performed to identify studies that compared MIP with and without ioPTH. Data were analyzed between August and September 2019.
STUDY SELECTION
Inclusion criteria consisted of randomized clinical trials and observational studies with a retrospective/prospective design, comparing MIP using ioPTH vs MIP not using ioPTH for treatment of primary hyperparathyroidism. Eligible studies had to present odds ratio (OR), risk ratio, or hazard ratio estimates (with 95% CI), standard errors, or number of events necessary to calculate these for the outcome of interest rate. Studies involving patients with secondary or tertiary hyperparathyroidism or those with multiple endocrine neoplasia syndrome were excluded.
DATA EXTRACTION
Two reviewers independently reviewed the literature according to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines. Dichotomous variables were pooled as ORs while continuous variables were compared using weighted mean differences. Quality assessment was performed using the Newcastle-Ottawa Scale.
MAIN OUTCOMES AND MEASURES
The primary outcome was rate of cure. Secondary outcomes included need for reoperation, need for bilateral neck exploration, morbidity, and length of surgery.
RESULTS
A total of 12 studies, involving 2290 patients with primary hyperparathyroidism, were eligible for inclusion. The median (SD) age of participants was 60.1 (11.8) years and 77.3% of participants were women. The median Newcastle-Ottawa score was 7. Patients who underwent MIP with ioPTH had higher cure rates (OR, 3.88; 95% CI, 2.12-7.10; P < .001). There was a greater need for reoperation in the group of patients who had surgery without ioPTH (OR, 0.40; 95% CI, 0.19-0.86; P = .02). There was a trend toward longer operating times/increased duration of surgery in the ioPTH group; however, this did not reach statistical significance (weighted mean difference, 21.62 minutes; 95% CI, -0.93 to 44.17 minutes; P = .06). The use of ioPTH was associated with higher rates of bilateral neck exploration (OR, 3.55; 95% CI, 1.27-9.92; P = .02).
CONCLUSIONS AND RELEVANCE
Use of ioPTH is associated with higher cure rates for patients with primary hyperparathyroidism undergoing MIP. Minimally invasive parathyroidectomy performed without ioPTH is associated with less conversion to bilateral neck exploration at initial surgery but with lower cure rates and an increased risk for reoperation.
TRIAL REGISTRATION
PROSPERO identifier: CRD42020148588.
Topics: Humans; Hyperparathyroidism, Primary; Intraoperative Care; Minimally Invasive Surgical Procedures; Parathyroid Hormone; Parathyroidectomy
PubMed: 33211086
DOI: 10.1001/jamaoto.2020.4021 -
The Cochrane Database of Systematic... Oct 2020Bilateral neck exploration (BNE) is the traditional approach to sporadic primary hyperparathyroidism. With the availability of the preoperative imaging techniques and... (Meta-Analysis)
Meta-Analysis
Minimally invasive parathyroidectomy guided by intraoperative parathyroid hormone monitoring (IOPTH) and preoperative imaging versus bilateral neck exploration for primary hyperparathyroidism in adults.
BACKGROUND
Bilateral neck exploration (BNE) is the traditional approach to sporadic primary hyperparathyroidism. With the availability of the preoperative imaging techniques and intraoperative parathyroid hormone assays, minimally invasive parathyroidectomy (MIP) is fast becoming the favoured surgical approach.
OBJECTIVES
To assess the effects of minimally invasive parathyroidectomy (MIP) guided by preoperative imaging and intraoperative parathyroid hormone monitoring versus bilateral neck exploration (BNE) for the surgical management of primary hyperparathyroidism.
SEARCH METHODS
We searched CENTRAL, MEDLINE, WHO ICTRP and ClinicalTrials.gov. The date of the last search of all databases was 21 October 2019. There were no language restrictions applied.
SELECTION CRITERIA
We included randomised controlled trials comparing MIP to BNE for the treatment of sporadic primary hyperparathyroidism in persons undergoing surgery for the first time.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened titles and abstracts for relevance. Two review authors independently screened for inclusion, extracted data and carried out risk of bias assessment. The content expert senior author resolved conflicts. We assessed studies for overall certainty of the evidence using the GRADE instrument. We conducted meta-analyses using a random-effects model and performed statistical analyses according to the guidelines in the latest version of the Cochrane Handbook for Systematic Reviews of Interventions.
MAIN RESULTS
We identified five eligible studies, all conducted in European university hospitals. They included 266 adults, 136 participants were randomised to MIP and 130 participants to BNE. Data were available for all participants post-surgery up to one year, with the exception of missing data for two participants in the MIP group and for one participant in the BNE group at one year. Nine participants in the MIP group and 11 participants in the BNE group had missing data at five years. No study had a low risk of bias in all risk of bias domains. The risk ratio (RR) for success rate (eucalcaemia) at six months in the MIP group compared to the BNE group was 0.98 (95% confidence interval (CI) 0.94 to 1.03; P = 0.43; 5 studies, 266 participants; very low-certainty evidence). A total of 132/136 (97.1%) participants in the MIP group compared with 129/130 (99.2%) participants in the BNE group were judged as operative success. At five years, the RR was 0.94 (95% CI 0.83 to 1.08; P = 0.38; 1 study, 77 participants; very low-certainty evidence). A total of 34/38 (89.5%) participants in the MIP group compared with 37/39 (94.9%) participants in the BNE group were judged as operative success. The RR for the total incidence of perioperative adverse events was 0.50, in favour of MIP (95% CI 0.33 to 0.76; P = 0.001; 5 studies, 236 participants; low-certainty evidence). Perioperative adverse events occurred in 23/136 (16.9%) participants in the MIP group compared with 44/130 (33.9%) participants in the BNE group. The 95% prediction interval ranged between 0.25 and 0.99. These adverse events included symptomatic hypocalcaemia, vocal cord palsy, bleeding, fever and infection. Fifteen of 104 (14.4%) participants experienced symptomatic hypocalcaemia in the MIP group compared with 26/98 (26.5%) participants in the BNE group. The RR for this event comparing MIP with BNE at two days was 0.54 (95% CI 0.32 to 0.92; P = 0.02; 4 studies, 202 participants). Statistical significance was lost in sensitivity analyses, with a 95% prediction interval ranging between 0.17 and 1.74. Five out of 133 (3.8%) participants in the MIP group experienced vocal cord paralysis compared with 2/128 (1.6%) participants in the BNE group. The RR for this event was 1.87 (95% CI 0.47 to 7.51; P = 0.38; 5 studies, 261 participants). The 95% prediction interval ranged between 0.20 and 17.87. The effect on all-cause mortality was not explicitly reported and could not be adequately assessed (very low-certainty evidence). There was no clear difference for health-related quality of life between the treatment groups in two studies, but studies did not report numerical data (very low-certainty evidence). There was a possible treatment benefit for MIP compared to BNE in terms of cosmetic satisfaction (very low-certainty evidence). The mean difference (MD) for duration of surgery comparing BNE with MIP was in favour of the MIP group (-18 minutes, 95% CI -31 to -6; P = 0.004; 3 studies, 171 participants; very low-certainty evidence). The 95% prediction interval ranged between -162 minutes and 126 minutes. The studies did not report length of hospital stay. Four studies reported intraoperative conversion rate from MIP to open procedure information. Out of 115 included participants, there were 24 incidences of conversion, amounting to a conversion rate of 20.8%.
AUTHORS' CONCLUSIONS
The success rates of MIP and BNE at six months were comparable. There were similar results at five years, but these were only based on one study. The incidence of perioperative symptomatic hypocalcaemia was lower in the MIP compared to the BNE group, whereas the incidence of vocal cord paralysis tended to be higher. Our systematic review did not provide clear evidence for the superiority of MIP over BNE. However, it was limited by low-certainty to very low-certainty evidence.
Topics: Adult; Bias; Humans; Hyperparathyroidism, Primary; Hypocalcemia; Minimally Invasive Surgical Procedures; Monitoring, Intraoperative; Neck; Neck Dissection; Operative Time; Parathyroid Hormone; Parathyroidectomy; Postoperative Complications; Quality of Life; Vocal Cord Paralysis
PubMed: 33085088
DOI: 10.1002/14651858.CD010787.pub2 -
Endocrine Connections Jul 2020Primary hyperparathyroidism (PHPT) is a common condition affecting people of all ages and is mainly treated with parathyroidectomy. Cinacalcet has been widely used in...
PURPOSE
Primary hyperparathyroidism (PHPT) is a common condition affecting people of all ages and is mainly treated with parathyroidectomy. Cinacalcet has been widely used in secondary or tertiary hyperparathyroidism, but the use of cinacalcet in PHPT is less clear.
METHODS
Searches were conducted in Medline and Embase for cinacalcet use in PHPT from induction to 10 April 2020. Articles and conferences abstracts describing the use of cinacalcet for PHPT in prospective or retrospective cohorts and randomized controlled trials restricted to English language only. We initially identified 1301 abstracts. Each article went extraction by two blinded authors on a structured proforma. Continuous outcomes were pooled with weight mean difference (WMD). Quality of included articles was assessed with Newcastle Ottwa Scale and Cochrane Risk of Bias 2.0.
RESULTS
Twenty-eight articles were included. Normalization rate of serum Ca levels was reported at 90% (CI: 0.82 to 0.96). Serum levels of Ca and PTH levels were significantly reduced (Ca, WMD: 1.647, CI: -1.922 to -1.371; PTH, WMD: -31.218, CI: -41.671 to -20.765) and phosphate levels significantly increased (WMD: 0.498, CI: 0.400 to 0.596) after cinacalcet therapy. The higher the baseline Ca levels, the greater Ca reduction with cinacalcet treatment. Age and gender did not modify the effect of cinacalcet on serum Ca levels.
CONCLUSION
The results from the meta-analysis support the use of cinacalcet as an alternative or bridging therapy to treat hypercalcemia in people with PHPT.
PubMed: 32621588
DOI: 10.1530/EC-20-0221 -
The Cochrane Database of Systematic... Oct 2019People who have chronic kidney disease (CKD) have important changes to bone structure, strength, and metabolism. Children experience bone deformity, pain, and delayed or... (Review)
Review
BACKGROUND
People who have chronic kidney disease (CKD) have important changes to bone structure, strength, and metabolism. Children experience bone deformity, pain, and delayed or impaired growth. Adults experience limb and vertebral fractures, avascular necrosis, and pain. The fracture risk after kidney transplantation is four times that of the general population and is related to Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD) occurring with end-stage kidney failure, steroid-induced bone loss, and persistent hyperparathyroidism after transplantation. Fractures may reduce quality of life and lead to being unable to work or contribute to community roles and responsibilities. Earlier versions of this review have found low certainty evidence for effects of treatment. This is an update of a review first published in 2005 and updated in 2007.
OBJECTIVES
This review update evaluates the benefits and harms of interventions for preventing bone disease following kidney transplantation.
SEARCH METHODS
We searched the Cochrane Kidney and Transplant Register of Studies up to 16 May 2019 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov.
SELECTION CRITERIA
RCTs and quasi-RCTs evaluating treatments for bone disease among kidney transplant recipients of any age were eligible.
DATA COLLECTION AND ANALYSIS
Two authors independently assessed trial risks of bias and extracted data. Statistical analyses were performed using random effects meta-analysis. The risk estimates were expressed as a risk ratio (RR) for dichotomous variables and mean difference (MD) for continuous outcomes together with the corresponding 95% confidence interval (CI). The primary efficacy outcome was bone fracture. The primary safety outcome was acute graft rejection. Secondary outcomes included death (all cause and cardiovascular), myocardial infarction, stroke, musculoskeletal disorders (e.g. skeletal deformity, bone pain), graft loss, nausea, hyper- or hypocalcaemia, kidney function, serum parathyroid hormone (PTH), and bone mineral density (BMD).
MAIN RESULTS
In this 2019 update, 65 studies (involving 3598 participants) were eligible; 45 studies contributed data to our meta-analyses (2698 participants). Treatments included bisphosphonates, vitamin D compounds, teriparatide, denosumab, cinacalcet, parathyroidectomy, and calcitonin. Median duration of follow-up was 12 months. Forty-three studies evaluated bone density or bone-related biomarkers, with more recent studies evaluating proteinuria and hyperparathyroidism. Bisphosphonate therapy was usually commenced in the perioperative transplantation period (within 3 weeks) and regardless of BMD. Risks of bias were generally high or unclear leading to lower certainty in the results. A single study reported outcomes among 60 children and adolescents. Studies were not designed to measure treatment effects on fracture, death or cardiovascular outcomes, or graft loss.Compared to placebo, bisphosphonate therapy administered over 12 months in transplant recipients may prevent fracture (RR 0.62, 95% CI 0.38 to 1.01; low certainty evidence) although the 95% CI included the possibility that bisphosphonate therapy might make little or no difference. Fracture events were principally vertebral fractures identified during routine radiographic surveillance. It was uncertain whether any other drug class decreased fracture (low or very low certainty evidence). It was uncertain whether interventions for bone disease in kidney transplantation reduce all-cause or cardiovascular death, myocardial infarction or stroke, or graft loss in very low certainty evidence. Bisphosphonate therapy may decrease acute graft rejection (RR 0.70, 95% CI 0.55 to 0.89; low certainty evidence), while it is uncertain whether any other treatment impacts graft rejection (very low certainty evidence). Bisphosphonate therapy may reduce bone pain (RR 0.20, 95% CI 0.04 to 0.93; very low certainty evidence), while it was very uncertain whether bisphosphonates prevent spinal deformity or avascular bone necrosis (very low certainty evidence). Bisphosphonates may increase to risk of hypocalcaemia (RR 5.59, 95% CI 1.00 to 31.06; low certainty evidence). It was uncertain whether vitamin D compounds had any effect on skeletal, cardiovascular, death, or transplant function outcomes (very low certainty or absence of evidence). Evidence for the benefits and harms of all other treatments was of very low certainty. Evidence for children and young adolescents was sparse.
AUTHORS' CONCLUSIONS
Bisphosphonate therapy may reduce fracture and bone pain after kidney transplantation, however low certainty in the evidence indicates it is possible that treatment may make little or no difference. It is uncertain whether bisphosphonate therapy or other bone treatments prevent other skeletal complications after kidney transplantation, including spinal deformity or avascular bone necrosis. The effects of bone treatment for children and adolescents after kidney transplantation are very uncertain.
PubMed: 31637698
DOI: 10.1002/14651858.CD005015.pub4 -
Kidney International Reports Feb 2019Calciphylaxis is a life-threatening complication of chronic kidney disease (CKD). To inform clinical practice, we performed a systematic review of case reports, case...
BACKGROUND
Calciphylaxis is a life-threatening complication of chronic kidney disease (CKD). To inform clinical practice, we performed a systematic review of case reports, case series, and cohort studies to synthesize the available treatment modalities and outcomes of calciphylaxis in patients with CKD.
METHODS
Electronic databases were searched for studies that examined the uses of sodium thiosulfate, surgical parathyroidectomy, calcimimetics, hyperbaric oxygen therapy, and bisphosphonates for calciphylaxis in patients with CKD, including end-stage renal disease. For cohort studies, the results were synthesized quantitatively by performing random-effects model meta-analyses.
RESULTS
A total of 147 articles met the inclusion criteria and were included in the systematic review. There were 90 case reports (90 patients), 20 case series (423 patients), and 37 cohort studies (343 patients). In the pooled cohorts, case series, and case reports, 50.3% of patients received sodium thiosulfate, 28.7% underwent surgical parathyroidectomy, 25.3% received cinacalcet, 15.3% underwent hyperbaric oxygen therapy, and 5.9% received bisphosphonates. For the subset of cohort studies, by meta-analysis, the pooled risk ratio for mortality was not significantly different among patients who received sodium thiosulfate (pooled risk ratio [RR] 0.89; 95% confidence interval [CI] 0.71-1.12), cinacalcet (pooled RR 1.04; 95% CI 0.75-1.42), hyperbaric oxygen therapy (pooled RR 0.89; 95% CI 0.71-1.12), and bisphosphonates (pooled RR 0.77; 95% CI 0.44-1.32), and those who underwent surgical parathyroidectomy (pooled RR 0.88; 95% CI 0.69-1.13).
CONCLUSION
This systematic review found no significant clinical benefit of the 5 most frequently used treatment modalities for calciphylaxis in patients with CKD. Randomized controlled trials are needed to test the efficacy of these therapies.
PubMed: 30775620
DOI: 10.1016/j.ekir.2018.10.002 -
BJS Open Dec 2018The majority of patients with primary hyperparathyroidism (PHPT) have a single overactive adenoma. Advances in preoperative imaging and surgical adjuncts have given rise... (Review)
Review
BACKGROUND
The majority of patients with primary hyperparathyroidism (PHPT) have a single overactive adenoma. Advances in preoperative imaging and surgical adjuncts have given rise to minimally invasive parathyroidectomy (MIP), with lower complication rates in comparison with bilateral neck exploration. Misdiagnosis and undertreatment of multiglandular disease, leading to potentially higher recurrence rates, remains a concern. This study evaluated risks of long-term (1 year or more) recurrence following 'targeted' MIP in PHPT.
METHODS
Multiple databases were searched for studies published between January 2004 and March 2017, looking at long-term outcomes (1 year or more) following targeted MIP for PHPT. English-language studies, with at least 50 patients and a mean follow-up of 1 year, were included.
RESULTS
A total of 5282 patients from 14 studies were included. Overall mean recurrence and cure rates were 1·6 (range 0-3·5) and 96·9 (95·5-100) per cent respectively. Mean follow-up was 33·5 (1-145) months. When intraoperative parathyroid hormone (PTH) measurements were not done, cure rates were higher (99·3 per cent versus 98·1 per cent with use of intraoperative PTH measurement; P < 0·001) and recurrence rates lower (0·2 versus 1·5 per cent respectively; P < 0·001).
CONCLUSION
Targeted MIP for a presumed single overactive adenoma was associated with very low recurrence rates, without the need for intraoperative PTH measurement when preoperative imaging studies were concordant. Targeted MIP should be encouraged.
PubMed: 30511037
DOI: 10.1002/bjs5.77 -
PloS One 2018Postoperative hypocalcemia is the most common complication of thyroidectomy. Incidental parathyroidectomy (IP) was thought to be associated with postoperative... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Postoperative hypocalcemia is the most common complication of thyroidectomy. Incidental parathyroidectomy (IP) was thought to be associated with postoperative hypocalcemia. However, according to previous studies, the risk factors and clinical outcomes of IP remain controversial.
METHODS
Eligible studies were searched in databases including PubMed, Web of Science, and EMBASE from January 1990 to September 2017. Articles focusing on the relationship between IP and postoperative hypocalcemia were included. The risk of publication bias was assessed using Begg's test and Egger's regression asymmetry test. Pooled analysis was performed to evaluate the effect of IP on postoperative hypocalcemia and related risk factors. Sensitivity analysis was also conducted to test the stability of our results. The effects of hypocalcemia type, permanent definition, IP incidence, total thyroidectomy, and malignancy operation were also examined using a further subgroup analysis.
RESULTS
Thirty-five studies were finally included in the analysis after an exhaustive literature review. Pathology data demonstrate that incidental parathyroidectomy occurred in various locations: intrathyroidal (2.2-50.0%), intracapsular (16.7-40.0%) and extracapsular (15.7-81.1%) regions. Overall, the analysis found that malignancy (RR = 1.60, 95% CI: 1.27 to 2.02; p< 0.0001), central neck dissection (RR = 2.35, 95% CI: 1.47 to 3.75; p = 0.0004), total thyroidectomy (RR = 1.42, 95% CI: 1.20 to 1.67; p< 0.0001) and reoperation (RR = 1.81, 95% CI: 1.20 to 2.75; p = 0.005) were significant risk factors of IP in thyroid surgery. There was an obvious effect of IP on temporary/permanent (RR = 1.59, 95% CI: 1.37 to 1.84; p< 0.0001) and permanent (RD = 0.0220, 95% CI: 0.0069 to 0.0370; p = 0.0042) postoperative hypocalcemia. Sensitivity analysis showed that these results were robust. The subgroup analysis found that IP played a significant role in both biochemical and clinical hypocalcemia in thyroidectomy (p < 0.0001 and p = 0.0003, separately). The association of IP and permanent hypocalcemia using different definitions (6 months or more than 12 months) was also confirmed by the analysis. IP increased the incidence of temporary/permanent and permanent hypocalcemia for cases undergoing total thyroidectomy (40.4% vs 24.8% and 5.8% vs 1.4%, respectively). Thyroidectomy with IP was associated with more permanent hypocalcemia (RR = 3.10, 95% CI: 2.01 to 4.78; p< 0.0001) in malignant cases but was not associated with temporary/permanent hypocalcemia.
CONCLUSIONS
Malignancy, central neck dissection, total thyroidectomy and reoperation were found to be significant risk factors of IP. IP increases the risk of postoperative hypocalcemia after thyroidectomy. We recommend a more meticulous intraoperative identification of parathyroid gland in thyroidectomy to reduce IP, particularly for total thyroidectomy and malignancy cases.
Topics: Humans; Hypocalcemia; Medical Errors; Parathyroid Glands; Parathyroidectomy; Postoperative Complications; Risk Factors; Thyroidectomy; Treatment Outcome
PubMed: 30412639
DOI: 10.1371/journal.pone.0207088 -
Endocrine, Metabolic & Immune Disorders... 2019Neurofibromatosis type 1 is an autosomal dominant disorder characterized by an increased incidence of tumors, including endocrine ones. Primary hyperparathyroidism can...
BACKGROUND
Neurofibromatosis type 1 is an autosomal dominant disorder characterized by an increased incidence of tumors, including endocrine ones. Primary hyperparathyroidism can be rarely caused by a parathyroid carcinoma; these patients are generally characterized by severe symptoms, large neck lesions and high levels of PTH and calcium. We report a case of hyperparathyroidism due to parathyroid carcinoma in a patient affected by neurofibromatosis type 1. A systematic review of the literature was also conducted.
PATIENT FINDINGS
A 56-year-old woman was referred for a 13 mm-nodular lesion of the neck incidentally discovered on ultrasound examination and mild hyperparathyroidism. A 99mTctetrofosmin/ pertechnetate subtraction scintigraphy was negative for parathyroid disease. Given the absence of suspicious ultrasound finding, a fine-needle aspiration cytology was performed with iPTH determination in the aspirate, confirming the parathyroid origin of the lesion. The patient underwent left inferior parathyroidectomy with intraoperative monitoring of iPTH and became normocalcemic. On histopathological examination, parathyroid carcinoma presenting at the resection margin was diagnosed, thus a surgery revision was requested.
CONCLUSION
Even if literature does not support a syndromic association between neurofibromatosis type 1 and primary hyperparathyroidism, the benefit of precociously diagnosing and treating this condition may outweigh costs associated with screening. This case report moreover demonstrates that sometimes clinical, laboratory and imaging aspects suspicious for cancer may be missing. A prompt referral to a high-volume center is crucial for the management of those cases of incidental histopathological diagnosis.
Topics: Female; Humans; Hyperparathyroidism; Middle Aged; Neurofibromatosis 1; Parathyroid Neoplasms
PubMed: 30198445
DOI: 10.2174/1871530318666180910123316 -
Journal of Comparative Effectiveness... Jul 2018Randomized controlled trials (RCTs) with clinical outcomes are considered the gold standard for regulatory approval. However, by design they are only able to answer a... (Meta-Analysis)
Meta-Analysis
AIM
Randomized controlled trials (RCTs) with clinical outcomes are considered the gold standard for regulatory approval. However, by design they are only able to answer a small number of clinical questions. Other high-quality studies are required for clinical decision-making. The EVOLVE was the largest RCT, evaluating the effects of cinacalcet on clinical outcomes among adult patients receiving maintenance dialysis suffering from secondary hyperparathyroidism. While the EVOLVE trial did not reach its primary end point, imbalance in subjects' age at randomization and discontinuation rates are two of the reasons that the lack of mortality benefit is in question. We undertook a systematic literature review and Bayesian meta-analysis combining randomized and observational studies on the estimated effects of the oral calcimimetic cinacalcet on clinical outcomes including all-cause mortality, cardiovascular-related mortality, hospitalization for cardiovascular events, fracture and parathyroidectomy among patients on maintenance dialysis.
METHODS
Data sources included MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials databases. RCTs and observational studies were included. Data extraction was completed by two authors independently and in duplicate determined the methodological quality of the studies and extracted data.
RESULTS
Of 564 unique citations identified, 16 studies were included: six observational studies and ten RCTs. Four high-quality studies (two observational and two RCTs) were deemed suitable for meta-analysis. Results indicated a statistically significant reduction in the risk of death associated with cinacalcet (hazard ratio: 0.83; 95% credible interval: 0.78-0.89).
CONCLUSION
The results of this meta-analysis indicate that treatment of secondary hyperparathyroidism with calcimimetic therapy may in fact reduce mortality among patients receiving maintenance dialysis. This finding provides justification for a well-designed and adequately powered randomized trial to definitively address the question.
Topics: Adult; Aged; Bayes Theorem; Calcimimetic Agents; Cinacalcet; Female; Fractures, Spontaneous; Hospitalization; Humans; Hyperparathyroidism, Secondary; Male; Middle Aged; Observational Studies as Topic; Parathyroidectomy; Randomized Controlled Trials as Topic; Renal Dialysis; Renal Insufficiency, Chronic; Treatment Outcome
PubMed: 29762046
DOI: 10.2217/cer-2018-0015